Compounds > ixazomib
Page last updated: 2024-11-13

ixazomib

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Description

ixazomib: a proteasome inhibitor with antineoplastic activity; MLN2238 is the biologically active form of MLN9708; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

ixazomib : A glycine derivative that is the amide obtained by formal condensation of the carboxy group of N-(2,5-dichlorobenzoyl)glycine with the amino group of [(1R)-1-amino-3-methylbutyl]boronic acid. The active metabolite of ixazomib citrate, it is used in combination therapy for treatment of multiple myeloma. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

FloraRankFlora DefinitionFamilyFamily Definition
GlycinegenusA non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter.[MeSH]FabaceaeThe large family of plants characterized by pods. Some are edible and some cause LATHYRISM or FAVISM and other forms of poisoning. Other species yield useful materials like gums from ACACIA and various LECTINS like PHYTOHEMAGGLUTININS from PHASEOLUS. Many of them harbor NITROGEN FIXATION bacteria on their roots. Many but not all species of beans belong to this family.[MeSH]

Cross-References

ID SourceID
PubMed CID25183872
CHEMBL ID2141296
CHEBI ID90942
SCHEMBL ID3742758
MeSH IDM000602996

Synonyms (65)

Synonym
NCGC00249611-01
D10130
ixazomib (usan)
mln 2238
mln-2238
MLN2238 ,
boronic acid, b-((1r)-1-((2-((2,5-dichlorobenzoyl)amino)acetyl)amino)-3-methylbutyl)-
ixazomib [usan:inn]
ixazomib [inn]
ixazomib
unii-71050168a2
71050168a2 ,
AKOS015995120
BCP9000953
bdbm50398609
CHEMBL2141296 ,
mln-9708 free base
1072833-77-2
NCGC00249611-03
ixazomib [usan]
((1r)-1-((2,5-dichlorobenzamido)acetamido)-3-methylbutyl)boronic acid
ixazomib [who-dd]
ixazomib [mi]
S2180
(r)-1-(2-(2,5-dichlorobenzamido)acetamido)-3-methylbutylboronic acid
BRD-K78659596-001-01-3
CS-1657
HY-10453
SCHEMBL3742758
CHEBI:90942 ,
n-[(1r)-1-borono-3-methylbutyl]-n(2)-(2,5-dichlorobenzoyl)glycinamide
(r)-(1-(2-(2,5-dichlorobenzamido)acetamido)-3-methylbutyl)boronic acid
[(1r)-1-[[2-[(2,5-dichlorobenzoyl)amino]acetyl]amino]-3-methyl-butyl]boronic acid
ixozamib
[(1r)-1-[[2-[(2,5-dichlorobenzoyl)amino]acetyl]amino]-3-methylbutyl]boronic acid
gtpl8450
AC-28456
DB09570
J-001749
EX-A547
mfcd18251438
[(1r)-1-{2-[(2,5-dichlorophenyl)formamido]acetamido}-3-methylbutyl]boronic acid
ixazomib(mln2238)
SW219743-1
mln2238(ixazomib)
BCP02410
ixazomib impurity
BCP24078
ixazomib (mln2238)
1072833-77-2 (free)
ixazomib (mln-2238)
Q20948663
AMY19380
CCG-264938
NCGC00249611-04
(r)-1-(2-(2,5-dichlorobenzamido)acetamido)-3-methylbutylboronic acid;ixazomib
A25328
AS-55976
nsc766907
nsc-766907
DTXSID701025662
EN300-7360341
n-((1r)-1-borono-3-methylbutyl)-n(2)-(2,5-dichlorobenzoyl)glycinamide
l01xx50
ixazomibum

Research Excerpts

Overview

Ixazomib (IXA) is an oral proteasome inhibitor (PI) used in combination with lenalidomide and dexamethasone for patients with relapsed and/or refractory multiple myeloma (RRMM) The drug is generally well tolerated; but the bone effect remains unknown.

ExcerptReferenceRelevance
"Ixazomib is an orally available proteasome inhibitor for multiple myeloma with adverse effects such as gastrointestinal symptoms, skin rashes, and thrombocytopenia reported in clinical trials and post-marketing surveillance, resulting in treatment discontinuation. "( Comprehensive Analysis of Ixazomib-Induced Adverse Events Using the Japanese Pharmacovigilance Database.
Fujiwara, M; Muroi, N; Shimizu, T; Uchida, M; Uesawa, Y; Yamaoka, K, 2022)		2.46
"Ixazomib is an oral proteasome inhibitor approved in combination with lenalidomide and dexamethasone for the treatment of relapsed/refractory multiple myeloma (MM). "( Population pharmacokinetic/pharmacodynamic joint modeling of ixazomib efficacy and safety using data from the pivotal phase III TOURMALINE-MM1 study in multiple myeloma patients.
Diderichsen, PM; Gupta, N; Hanley, MJ; Labotka, R; Srimani, JK; Venkatakrishnan, K, 2022)		2.41
"Ixazomib is an effective and welltolerated MM drug. "( An update on the safety of ixazomib for the treatment of multiple myeloma.
Goel, U; Kumar, S, 2022)		2.46
"Ixazomib is a new-generation, oral PI that is generally well tolerated; however, its bone effect remains unknown."( Increased Bone Volume by Ixazomib in Multiple Myeloma: 3-Month Results from an Open Label Phase 2 Study.
Abildgaard, N; Andersen, CW; Asmussen, JT; Diaz-delCastillo, M; Gundesen, MT; Kristensen, IB; Levin Andersen, T; Lund, T; Møller, HEH; Nielsen, AL; Nyvold, CG; Vinholt, PJ, 2023)		1.93
"Ixazomib is a second-generation oral proteasome inhibitor."( Ixazomib - lenalidomide - dexamethason in heavily pretreated multiple myeloma patients - case reports.
Štork, M, 2023)		3.07
"Ixazomib is a feasible and effective maintenance option for prolonging PFS across this heterogeneous patient population."( Ixazomib Versus Placebo as Postinduction Maintenance Therapy in Newly Diagnosed Multiple Myeloma Patients: An Analysis by Age and Frailty Status of the TOURMALINE-MM4 Study.
Benjamin, R; Bringhen, S; C de Farias, DL; Cain, LE; Cherepanov, D; Dimopoulos, MA; Grosicki, S; Labotka, RJ; Manne, S; Min, CK; Pour, L; Rajkumar, SV; Vorog, A; Wang, B, 2023)		3.8
"Ixazomib (IXA) is an oral proteasome inhibitor (PI) used in combination with lenalidomide and dexamethasone (IXA-Rd) for patients with relapsed and/or refractory multiple myeloma (RRMM). "( Real-world effectiveness of ixazomib combined with lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: the REMIX study.
Barrak, J; Benboubker, L; Calmettes, C; Charvet-Rumpler, A; Chouaid, C; Clement-Filliatre, L; Honeyman, F; Hulin, C; Karlin, L; Laribi, K; Leleu, X; Macro, M; Maloisel, F; Richez, V; Stoppa, AM; Vincent, L; Zerazhi, H, 2023)		2.65
"Ixazomib is an efficacious and tolerable option for post-ASCT maintenance."( Adverse event management in the TOURMALINE-MM3 study of post-transplant ixazomib maintenance in multiple myeloma.
Beksaç, M; Czorniak, M; de Arriba de la Fuente, F; Dimopoulos, MA; Gulbrandsen, N; Hájek, R; Kaiser, M; Labotka, R; Li, C; Mateos, MV; Moreau, P; Rajkumar, SV; Schjesvold, F; Spencer, A; Suryanarayan, K; Teng, Z; West, S, 2020)		1.51
"Ixazomib is an oral, second-generation, proteasome inhibitor that has been shown in preclinical models to prevent GVHD."( Ixazomib for Chronic Graft-versus-Host Disease Prophylaxis following Allogeneic Hematopoietic Cell Transplantation.
Abedin, S; Chhabra, S; D'Souza, A; Dhakal, B; Douglas Rizzo, J; Drobyski, WR; Fenske, TS; Hamadani, M; Hari, PN; Horowitz, MM; Jerkins, JH; Pasquini, MC; Runaas, L; Saber, W; Shah, NN; Shaw, BE; Tang, X; Thompson, R; Visotcky, A; Zhang, MJ; Zhu, F, 2020)		2.72
"Ixazomib is a next generation inhibitor of the 20S proteasome and is thought to be an effective treatment for those who have relapsed from bortezomib."( The MUK eight protocol: a randomised phase II trial of cyclophosphamide and dexamethasone in combination with ixazomib, in relapsed or refractory multiple myeloma (RRMM) patients who have relapsed after treatment with thalidomide, lenalidomide and a prote
Auner, HW; Bailey, L; Brown, S; Brudenell Straw, F; Cook, G; Cook, M; Dawkins, B; Flanagan, L; Hinsley, S; Kaiser, MF; McKee, S; Meads, D; Reed, S; Sherratt, D; Walker, K, 2020)		1.49
"Ixazomib is a selective, effective, and reversible inhibitor of 20S proteasome and is approved for the treatment of multiple myeloma. "( Ixazomib inhibits myeloma cell proliferation by targeting UBE2K.
Chen, X; Chen, Y; Dong, Z; Huang, J; Ma, L; Su, J; Tian, L; Wang, Q; Xiao, P, 2021)		3.51
"Ixazomib-Rd is a feasible option for certain patients who can benefit from an all-oral triplet combination."( Oral ixazomib, lenalidomide, and dexamethasone for transplant-ineligible patients with newly diagnosed multiple myeloma.
Bahlis, NJ; Benboubker, L; Facon, T; Karlin, L; Kumar, SK; Lonial, S; Moreau, P; Offner, F; Rajkumar, SV; Richardson, PG; Rifkin, RM; Rigaudeau, S; Rodon, P; Shibayama, H; Suzuki, K; Twumasi-Ankrah, P; Venner, CP; Voog, E; White, DJ; Yoon, SS; Yung, G; Zhang, X, 2021)		1.86
"Ixazomib (IXA) is an orally available proteasome inhibitor, with an improved safety profile compared to Bortezomib (BTZ)."( Pre-Clinical Evaluation of the Proteasome Inhibitor Ixazomib against Bortezomib-Resistant Leukemia Cells and Primary Acute Leukemia Cells.
Cloos, J; Jansen, G; Kaspers, GJL; Kwidama, ZJ; Roeten, MSF; Segerink, WH; Ter Huizen, G; van Meerloo, J; Zweegman, S, 2021)		1.59
"Ixazomib is an oral proteasome inhibitor with a wide safety profile that has demonstrated immunomodulatory properties, inhibition of pro-inflammatory cytokines, and anti-tumor activity."( Oral Proteasome Inhibitor Ixazomib for Switch-Maintenance Prophylaxis of Recurrent or Late Acute and Chronic Graft-versus-Host Disease after Day 100 in Allogeneic Stem Cell Transplantation.
Cho, C; Dahi, P; Devlin, SM; Flynn, L; Giralt, S; Lee, J; Murray, F; Perales, MA; Ponce, DM; Rodriguez, N; Sauter, C; Soto, C, 2021)		1.64
"Ixazomib is a second-generation proteasome inhibitor that has been approved in the combination treatment of multiple myeloma and is currently under clinical investigation for the management of Waldenstrom's macroglobulinemia. "( Ixazomib-induced cutaneous necrotizing vasculitis.
Alloo, A; Castillo, JJ; Granter, SR; Jadeja, SM; Khosravi, H; LeBoeuf, NR; Richardson, PG, 2018)		3.37
"Ixazomib is a first-in-class oral proteasome inhibitor to receive regulatory approval for the treatment of multiple myeloma."( Acute Pancreatitis Associated with Ixazomib in a Multiple Myeloma Patient.
Lee, HC; Orlowski, RZ; Steiner, RE, )		1.13
"Ixazomib is a boron-containing selective and reversible proteasome inhibitor that demonstrated antimyeloma activity with excellent safety profile."( Ixazomib in the management of relapsed multiple myeloma.
Moreau, P; Touzeau, C, 2018)		2.64
"Ixazomib is an oral proteasome inhibitor used in combination with lenalidomide plus dexamethasone (IXA-LEN-DEX) and licensed for relapsed or refractory multiple myeloma. "( Ixazomib for Relapsed or Refractory Multiple Myeloma: Review from an Evidence Review Group on a NICE Single Technology Appraisal.
Armoiry, X; Clarke, A; Connock, M; Cummins, E; Melendez-Torres, GJ; Royle, P; Tsertsvadze, A, 2018)		3.37
"Ixazomib is a selective, potent, and reversible inhibitor of the 20S proteasome, and preferentially binds to and inhibits the β5 chymotrypsin-like proteolytic site."( Clinical Pharmacology of Ixazomib: The First Oral Proteasome Inhibitor.
Gupta, N; Hanley, MJ; Harvey, RD; Labotka, R; Venkatakrishnan, K; Xia, C, 2019)		1.54
"Ixazomib is a selective and reversible inhibitor of the proteasome, which has been mainly investigated in the treatment of multiple myeloma."( Ixazomib in combination with carboplatin in pretreated women with advanced triple-negative breast cancer, a phase I/II trial of the AGMT (AGMT MBC-10 trial).
Balic, M; Bartsch, R; Burgstaller, S; Egle, D; Fuchs, D; Gampenrieder, SP; Greil, R; Melchardt, T; Mlineritsch, B; Petru, E; Petzer, A; Rinnerthaler, G; Rossmann, D; Rumpold, H; Singer, CF; Ulmer, H, 2018)		2.64
"Ixazomib is a new, orally administered, reversible proteasome inhibitor which is under investigation for the treatment of refractory/relapsed multiple myeloma (MM), systemic light chain amyloidosis (AL) and Waldenström macroglobulinemia (WM). "( Ixazomib: an investigational drug for the treatment of lymphoproliferative disorders.
Rydygier, D; Smolewski, P, 2019)		3.4
"Ixazomib is an investigational, orally bioavailable 20S proteasome inhibitor."( Phase 1 study of weekly dosing with the investigational oral proteasome inhibitor ixazomib in relapsed/refractory multiple myeloma.
Bensinger, WI; Berenson, JR; Berg, D; Di Bacco, A; Gupta, N; Hui, AM; Kumar, SK; Niesvizky, R; Reeder, CB; Shou, Y; Yu, J; Zimmerman, TM, 2014)		1.35
"Ixazomib is an investigational proteasome inhibitor that has shown preclinical activity in lymphoma models. "( Phase 1 dose-escalation study of IV ixazomib, an investigational proteasome inhibitor, in patients with relapsed/refractory lymphoma.
Assouline, SE; Chang, J; Cheson, BD; Di Bacco, A; Gupta, N; Hamburg, S; Hui, AM; Martin, P; Reyes, R; Rifkin, R; Shou, Y; Yu, J, 2014)		2.12
"Ixazomib is an investigational, oral, proteasome inhibitor with promising anti-myeloma effects and low rates of peripheral neuropathy."( Safety and tolerability of ixazomib, an oral proteasome inhibitor, in combination with lenalidomide and dexamethasone in patients with previously untreated multiple myeloma: an open-label phase 1/2 study.
Berdeja, JG; Berg, D; Di Bacco, A; Estevam, J; Gupta, N; Hamadani, M; Hari, P; Hui, AM; Kaufman, JL; Kumar, SK; Laubach, JP; Liao, E; Lonial, S; Niesvizky, R; Rajkumar, V; Richardson, PG; Roy, V; Stewart, AK; Vescio, R, 2014)		1.42
"Ixazomib is an investigational proteasome inhibitor with demonstrated antitumor activity in xenograft models of multiple myeloma (MM), lymphoma, and solid tumors. "( Phase 1 study of ixazomib, an investigational proteasome inhibitor, in advanced non-hematologic malignancies.
Berg, D; Berger, AJ; Di Bacco, A; Gao, F; Gupta, N; Hui, AM; Infante, JR; Kalebic, T; Kauh, JS; Lin, J; Liu, G; Siu, LL; Smith, DC; Sullivan, D; Thompson, JA; Tirrell, S; Vlahovic, G, 2015)		2.2
"Ixazomib is an investigational, reversible 20S proteasome inhibitor. "( The investigational proteasome inhibitor ixazomib for the treatment of multiple myeloma.
Anderson, KC; Gupta, N; Hui, AM; Kumar, S; Laubach, JP; Moreau, P; Richardson, PG; San Miguel, JF, 2015)		2.13
"Ixazomib is a second-generation PI with improved activity over other PIs."( Spotlight on ixazomib: potential in the treatment of multiple myeloma.
Azab, AK; Ghazarian, RN; Kusdono, HD; Luderer, MJ; Muz, B; Ou, M, 2016)		1.52
"Ixazomib (Ninlaro(®)) is an orally bioavailable, reversible proteasome inhibitor developed by Millennium Pharmaceuticals, Inc. "( Ixazomib: First Global Approval.
Shirley, M, 2016)		3.32
"Ixazomib is an oral proteasome inhibitor that is currently being studied for the treatment of multiple myeloma."( Oral Ixazomib, Lenalidomide, and Dexamethasone for Multiple Myeloma.
Bahlis, NJ; Baker, BW; Berg, DT; Buadi, FK; Cavo, M; Di Bacco, A; Ganly, P; Garderet, L; Gimsing, P; Grzasko, N; Hansson, M; Hui, AM; Jackson, SR; Kumar, S; Laubach, JP; Lin, J; Masszi, T; Moreau, P; Palumbo, A; Pour, L; Richardson, PG; Sandhu, I; Simpson, DR; Stoppa, AM; Touzeau, C; van de Velde, H, 2016)		2.39
"Ixazomib is an orally bioavailable proteasome inhibitor with a rapid proteasome dissociation rate."( Ixazomib suppresses human dendritic cell and modulates murine graft-versus-host disease in a schedule-dependent fashion.
Abdel-Mageed, S; Al-Homsi, AS; Cole, K; Feng, Y; Goodyke, A; McLane, M; Muilenburg, M, 2017)		2.62

Effects

ExcerptReferenceRelevance
"Ixazomib has been approved in several countries as single-agent maintenance therapy in newly diagnosed multiple myeloma, in both posttransplant and transplant-ineligible settings, based on two phase III studies. "( Dose Titration of Ixazomib Maintenance Therapy in Transplant-Ineligible Multiple Myeloma: Exposure-Response Analysis of the TOURMALINE-MM4 Study.
Diderichsen, PM; Gupta, N; Hanley, MJ; Labotka, R; Srimani, JK, 2023)		2.69

Treatment

Ixazomib treatment resulted in significant metabolic regulation. Some of these changes were specific to KRAS WT tumors. Treatment did not adversely affect patient-reported quality-of-life scores across age and frailty status subgroups.

ExcerptReferenceRelevance
"In ixazomib-treated TCL and HL cells, transient inhibition followed by full recovery of proteasomal activity observed was accompanied by induction of proteasomal gene expression with NFE2L2 (also termed NRF2) as a prominent upstream regulator."( Combinatorial ixazomib and belinostat therapy induces NFE2L2-dependent apoptosis in Hodgkin and T-cell lymphoma.
Beheshti, A; David, KA; Evens, AM; McDonald, JT; Passero, FC; Ravi, D, 2020)		1.43
"Ixazomib treatment resulted in significant metabolic regulation, and some of these changes were specific to KRAS WT tumors."( KRAS Genotype Correlates with Proteasome Inhibitor Ixazomib Activity in Preclinical In Vivo Models of Colon and Non-Small Cell Lung Cancer: Potential Role of Tumor Metabolism.
Amidon, B; Bannerman, B; Berger, AJ; Bernard, H; Chattopadhyay, N; Donelan, J; Galvin, K; Garnsey, J; Hales, P; Hather, G; Jordan, K; Koenig, E; Maldonado Lopez, A; Manfredi, M; Rhodes, N; Stringer, B; Tirrell, S; Xia, C; Yang, Y, 2015)		1.39
"Treatment with ixazomib, an oral proteasome inhibitor, has demonstrated better efficacy and safety profile without increasing the toxicity."( The MODIFY Study Protocol: An Open-Label, Single-Arm, Multicenter, Prospective Pragmatic Study of Ixazomib-Based Triple-Drug Therapy in Chinese Patients with Multiple Myeloma.
Chen, W; Li, L; Liu, A, 2023)		1.47
"Treatment with ixazomib versus placebo did not adversely affect patient-reported quality-of-life scores across age and frailty status subgroups."( Ixazomib Versus Placebo as Postinduction Maintenance Therapy in Newly Diagnosed Multiple Myeloma Patients: An Analysis by Age and Frailty Status of the TOURMALINE-MM4 Study.
Benjamin, R; Bringhen, S; C de Farias, DL; Cain, LE; Cherepanov, D; Dimopoulos, MA; Grosicki, S; Labotka, RJ; Manne, S; Min, CK; Pour, L; Rajkumar, SV; Vorog, A; Wang, B, 2023)		2.69
"Treatment with ixazomib had no toxic effect on the mdx mouse."( Ixazomib, an oral proteasome inhibitor, exhibits potential effect in dystrophin-deficient mdx mice.
Bertassoli, BM; Carvalho, AAS; Feder, D; Fonseca, FLA; Hermes, TA; Micheletto, MLJ; Perez, MM; Petri, G, 2021)		2.4

Toxicity

Ixazomib is an orally available proteasome inhibitor for multiple myeloma. Adverse effects such as gastrointestinal symptoms, skin rashes and thrombocytopenia reported in clinical trials and post-marketing surveillance. Four dose-limiting toxic events were noted in phase 1.

ExcerptReferenceRelevance
" Four dose-limiting toxic events were noted in phase 1: one at a dose of ixazomib of 2·97 mg/m(2) and three at 3·95 mg/m(2)."( Safety and tolerability of ixazomib, an oral proteasome inhibitor, in combination with lenalidomide and dexamethasone in patients with previously untreated multiple myeloma: an open-label phase 1/2 study.
Berdeja, JG; Berg, D; Di Bacco, A; Estevam, J; Gupta, N; Hamadani, M; Hari, P; Hui, AM; Kaufman, JL; Kumar, SK; Laubach, JP; Liao, E; Lonial, S; Niesvizky, R; Rajkumar, V; Richardson, PG; Roy, V; Stewart, AK; Vescio, R, 2014)		0.93
" Twenty-one (49%) patients had at least one drug-related grade ≥3 adverse event (AE); the most common were neutropenia (19%), diarrhea (14%), and thrombocytopenia (12%)."( Pharmacokinetics and safety of ixazomib plus lenalidomide-dexamethasone in Asian patients with relapsed/refractory myeloma: a phase 1 study.
Chim, CS; Chng, WJ; Esseltine, DL; Goh, YT; Gupta, N; Hanley, MJ; Hui, AM; Kim, K; Lee, JH; Min, CK; Venkatakrishnan, K; Wong, RS; Yang, H, 2015)		0.7
" Methods Logistic regression was used to investigate relationships between ixazomib plasma exposure (area under the curve/day; derived from individual apparent clearance values from a published population pharmacokinetic analysis) and safety/efficacy outcomes (hematologic [grade ≥ 3 vs ≤ 2] or non-hematologic [grade ≥ 2 vs ≤ 1] adverse events [AEs], and clinical benefit [≥stable disease vs progressive disease]) using phase 1 data in relapsed/refractory MM (NCT00963820; N = 44)."( Exposure-safety-efficacy analysis of single-agent ixazomib, an oral proteasome inhibitor, in relapsed/refractory multiple myeloma: dose selection for a phase 3 maintenance study.
Gupta, N; Hui, AM; Labotka, R; Liu, G; Venkatakrishnan, K, 2016)		0.92
" PK and adverse events (AEs) were assessed after a single 3 mg dose of ixazomib."( A pharmacokinetics and safety phase 1/1b study of oral ixazomib in patients with multiple myeloma and severe renal impairment or end-stage renal disease requiring haemodialysis.
Badros, A; Berdeja, J; Chari, A; Gupta, N; Hanley, MJ; Harvey, RD; Hui, AM; Kukreti, V; Lipe, B; Qian, M; Venkatakrishnan, K; Yang, H; Zhang, X, 2016)		0.91
" Areas covered: This review focuses on the safety data from clinical trials for the three approved PIs and how to manage adverse effects."( Safety of proteasome inhibitors for treatment of multiple myeloma.
Lonial, S; Panjic, EH; Schlafer, D; Shah, KS, 2017)		0.46
" We focused on adverse events associated with such agents and described how they should be managed."( Management of adverse events induced by next-generation immunomodulatory drug and proteasome inhibitors in multiple myeloma.
Boccadoro, M; Bonello, F; Larocca, A; Salvini, M, 2017)		0.46
" Safety data from TOURMALINE-MM1 are reviewed and guidance for managing clinically relevant adverse events associated with IRd is provided."( Management of adverse events associated with ixazomib plus lenalidomide/dexamethasone in relapsed/refractory multiple myeloma.
Avivi, I; Berg, D; Einsele, H; Esseltine, DL; Gupta, N; Hájek, R; Hari, P; Kumar, S; Liberati, AM; Lin, J; Lonial, S; Ludwig, H; Masszi, T; Mateos, MV; Minnema, MC; Moreau, P; Richardson, PG; Romeril, K; Shustik, C; Spencer, A, 2017)		0.71
" The overall incidence of adverse events (AEs) was similar in IRd and placebo-Rd groups."( [Safety and management of adverse events of ixazomib/lenalidomide/dexamethasone therapy in Japanese patients with relapsed/refractory multiple myeloma].
Aotsuka, N; Berg, D; Handa, H; Iida, S; Ishida, T; Izumi, T; Kase, Y; Komeno, T; Soeda, J; Sunami, K, )		0.39
" The adverse events were usually mild, none leading to permanent drug interruptions."( Real World Efficacy and Safety Results of Ixazomib Lenalidomide and Dexamethasone Combination in Relapsed/Refractory Multiple Myeloma: Data Collected from the Hungarian Ixazomib Named Patient Program.
Alizadeh, H; Bátai, Á; Deák, B; Demeter, J; Illés, Á; Kosztolányi, S; Mikala, G; Nagy, Z; Pető, M; Plander, M; Schneider, T; Szendrei, T; Szomor, Á; Varga, G; Váróczy, L, 2019)		0.78
" Fourteen patients (9%) discontinued IRd due to adverse events/toxicity in the absence of disease progression."( Real-world effectiveness and safety of ixazomib-lenalidomide-dexamethasone in relapsed/refractory multiple myeloma.
Aitchison, R; Dimopoulos, MA; Gavriatopoulou, M; Hajek, R; Jelinek, T; Jenner, MW; Kastritis, E; Katodritou, E; Kothari, J; Kotsopoulou, M; Maouche, N; Minarik, J; Ntanasis-Stathopoulos, I; Pika, T; Plonkova, H; Ramasamy, K; Terpos, E; Vallance, GD; Zomas, A, 2020)		0.83
" We report additional safety data from TOURMALINE-MM3 to inform adverse event (AE) management recommendations."( Adverse event management in the TOURMALINE-MM3 study of post-transplant ixazomib maintenance in multiple myeloma.
Beksaç, M; Czorniak, M; de Arriba de la Fuente, F; Dimopoulos, MA; Gulbrandsen, N; Hájek, R; Kaiser, M; Labotka, R; Li, C; Mateos, MV; Moreau, P; Rajkumar, SV; Schjesvold, F; Spencer, A; Suryanarayan, K; Teng, Z; West, S, 2020)		0.79
"The incidence of grade 3 or more haematological and grade 2 or more non-haematological adverse events was lower in the dose-escalation group than in the standard-dose group, and only that of diarrhoea was significantly lower."( Safety and Effectiveness of Ixazomib Dose-escalating Strategy in Ixazomib-Lenalidomide-Dexamethasone Treatment for Relapsed/Refractory Multiple Myeloma.
Boku, S; Higai, K; Kagoo, T; Niijima, D; Ogawa, C; Ohashi, Y; Tani, K; Ueno, H; Yachi, Y; Yano, T; Yatabe, M; Yokoyama, A, )		0.43
"A dose-escalation strategy to optimise ixazomib dosing may reduce treatment interruption due to adverse events without compromising its antitumor activity."( Safety and Effectiveness of Ixazomib Dose-escalating Strategy in Ixazomib-Lenalidomide-Dexamethasone Treatment for Relapsed/Refractory Multiple Myeloma.
Boku, S; Higai, K; Kagoo, T; Niijima, D; Ogawa, C; Ohashi, Y; Tani, K; Ueno, H; Yachi, Y; Yano, T; Yatabe, M; Yokoyama, A, )		0.69
" In routine practice, few patients received ixazomib-based induction therapy due to reasons including (1) patients' preference on oral regimens, (2) concerns on adverse events (AEs) of other intravenous/subcutaneous regimens, (3) requirements for less center visits, and (4) fears of COVID-19 and other infectious disease exposures."( Ixazomib-based frontline therapy in patients with newly diagnosed multiple myeloma in real-life practice showed comparable efficacy and safety profile with those reported in clinical trial: a multi-center study.
Bao, L; Chen, B; Ding, K; Fu, C; Hua, L; Huang, Y; Li, B; Li, J; Liu, P; Luo, J; Wang, L; Wang, S; Wang, W; Wu, G; Xia, Z; Xu, T; Yang, W; Yang, Y; Zhang, W; Zhou, X, 2020)		2.26
"Prolonged survival and expanded treatment options in myeloma patients have led to adverse events associated with treatment getting increased attention."( Ixazomib-associated cardiovascular adverse events in multiple myeloma: a systematic review and meta-analysis.
Chen, Z; Li, R; Ling, Y; Zhao, Y; Zhong, J, 2022)		2.16
" The patient treatment course, including adverse events (AEs), was reported."( Safety Profile of Ixazomib in Patients with Relapsed/Refractory Multiple Myeloma in Japan: An All-case Post-marketing Surveillance.
Chou, T; Hashimoto, M; Hiraizumi, M; Hoshino, M; Kakimoto, Y; Shimizu, K, 2022)		1.06
" In terms of adverse reactions, our analysis revealed higher incidences of grade 3-4 thrombocytopenia (RR = 7."( Efficacy and safety of ixazomib maintenance therapy for patients with multiple myeloma: a meta-analysis.
Chen, H; Shao, C; Sun, C; Wang, Y; Zheng, C, 2021)		0.93
" The most common grade 3/4 adverse events included neutropenia, leukopenia, thrombocytopenia, lung infections, diarrhea, and maculopapular rash."( Safety and Efficacy of Combination Maintenance Therapy with Ixazomib and Lenalidomide in Patients with Posttransplant Myeloma.
Bashir, Q; Feng, L; Huo, XJ; Lee, HC; Manasanch, EM; Morphey, A; Olsem, J; Orlowski, RZ; Patel, KK; Qazilbash, MH; Shah, JJ; Thomas, SK; Weber, DM, 2022)		0.96
"The addition of ixazomib to lenalidomide maintenance demonstrated a better than expected PFS compared with historical data using lenalidomide alone and was safe and tolerable."( Safety and Efficacy of Combination Maintenance Therapy with Ixazomib and Lenalidomide in Patients with Posttransplant Myeloma.
Bashir, Q; Feng, L; Huo, XJ; Lee, HC; Manasanch, EM; Morphey, A; Olsem, J; Orlowski, RZ; Patel, KK; Qazilbash, MH; Shah, JJ; Thomas, SK; Weber, DM, 2022)		1.31
"Ixazomib is an orally available proteasome inhibitor for multiple myeloma with adverse effects such as gastrointestinal symptoms, skin rashes, and thrombocytopenia reported in clinical trials and post-marketing surveillance, resulting in treatment discontinuation."( Comprehensive Analysis of Ixazomib-Induced Adverse Events Using the Japanese Pharmacovigilance Database.
Fujiwara, M; Muroi, N; Shimizu, T; Uchida, M; Uesawa, Y; Yamaoka, K, 2022)		2.46
"Herein, we aimed to determine the frequency and risk of AEs associated with ixazomib in Japanese patients using the Japanese Adverse Event Reporting Database (JADER)."( Comprehensive Analysis of Ixazomib-Induced Adverse Events Using the Japanese Pharmacovigilance Database.
Fujiwara, M; Muroi, N; Shimizu, T; Uchida, M; Uesawa, Y; Yamaoka, K, 2022)		1.25
" It does not have long-term cumulative toxicities, and the most adverse events are mild and manageable."( An update on the safety of ixazomib for the treatment of multiple myeloma.
Goel, U; Kumar, S, 2022)		1.02
" Non-hematologic adverse events (AEs) were more common than hematologic AEs."( Real-world toxicity and effectiveness of ixazomib, lenalidomide, and dexamethasone in Korean patients with relapsed and/or refractory multiple myeloma.
Jo, JC; Kim, HR; Kim, K; Kim, SH; Lee, JH; Lee, JJ; Lee, JY; Min, CK; Moon, JH; Shin, HJ, 2023)		1.18
" Treatment-naïve patients with iNHL needing therapy received oral ixazomib 4 mg weekly until progressive disease or unacceptable adverse events."( Efficacy, safety, and molecular response predictors of oral ixazomib and short-course rituximab in untreated iNHL.
Coffey, DG; Cowan, AJ; Fromm, JR; Gooley, TA; Gopal, AK; Graf, SA; Greninger, AL; Libby, EN; Lynch, RC; Rasmussen, H; Shadman, M; Smith, SD; Ujjani, CS; Warren, EH, 2023)		1.39
" The risk of cardiac adverse events (CAEs) with PIs has been documented with bortezomib and carfilzomib; however, only a few studies have been reported on ixazomib."( Cardiac Adverse Events Associated with Multiple Myeloma Patients Treated with Proteasome Inhibitors.
Endo, M; Fujiwara, M; Goto, M; Shimizu, T; Uchida, M, 2023)		1.11
"This study aimed to determine the safety signals of adverse events related to CAEs, the effect of concomitant medications, the time to the occurrence of CAEs, and the incidence of fatal clinical outcomes after the occurrence of CAEs for three PIs using the US Pharmacovigilance database."( Cardiac Adverse Events Associated with Multiple Myeloma Patients Treated with Proteasome Inhibitors.
Endo, M; Fujiwara, M; Goto, M; Shimizu, T; Uchida, M, 2023)		0.91
"We examined 1,567,240 cases of 231 drugs registered as anticancer drugs in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database from January 1997 to March 2021."( Cardiac Adverse Events Associated with Multiple Myeloma Patients Treated with Proteasome Inhibitors.
Endo, M; Fujiwara, M; Goto, M; Shimizu, T; Uchida, M, 2023)		0.91
" However, no adverse event CAE signals were observed with ixazomib treatment."( Cardiac Adverse Events Associated with Multiple Myeloma Patients Treated with Proteasome Inhibitors.
Endo, M; Fujiwara, M; Goto, M; Shimizu, T; Uchida, M, 2023)		1.15
" Patients' treatment responses, overall response rate, progression-free survival rate, and adverse events were recorded."( Real-world data on the effectiveness and safety of Ixazomib-Lenalidomide-Dexamethasone therapy in relapsed/refractory multiple myeloma patients: a multicenter experience in Turkey.
Albayrak, M; Altuntas, F; Bakırtaş, M; Başcı, S; Basturk, A; Çakar, MK; Dal, MS; Dogu, MH; Ekinci, O; Eser, B; Giden, AO; Gulturk, E; Hacıbekiroglu, T; Kalpakci, Y; Korkmaz, S; Miskioglu, M; Ozatli, D; Serin, I; Ulas, T; Yiğenoğlu, TN, 2023)		1.16
" Frequent (≥10% incidence) grade ≥3 treatment emergent adverse events were decreased neutrophil and platelet counts (n=7 [16%] each)."( Efficacy and Safety of Ixazomib Plus Lenalidomide and Dexamethasone Following Injectable PI-Based Therapy in Relapsed/Refractory Multiple Myeloma.
Abe, Y; Chou, T; Handa, H; Ito, S; Mori, I; Sasaki, M; Shinozaki, T; Suzuki, K; Takezako, N; Yoshida, T, 2023)		1.22

Pharmacokinetics

This population pharmacokinetic analysis of the investigational oral proteasome inhibitor ixazomib assessed the feasibility of switching from body surface area (BSA)-based to fixed dosing. The clinical drug-drug interaction study results were reconciled well by a physiologically based pharmacokinetics model that incorporated a minor contribution of CYP3A.

ExcerptReferenceRelevance
"This population pharmacokinetic analysis of the investigational oral proteasome inhibitor ixazomib assessed the feasibility of switching from body surface area (BSA)-based to fixed dosing, and the impact of baseline covariates on ixazomib pharmacokinetics."( Switching from body surface area-based to fixed dosing for the investigational proteasome inhibitor ixazomib: a population pharmacokinetic analysis.
Esseltine, DL; Gupta, N; Hui, AM; Venkatakrishnan, K; Zhao, Y, 2015)		0.85
" This study was conducted to investigate the pharmacokinetic and safety profiles of ixazomib, administered with lenalidomide-dexamethasone, in East Asian patients with relapsed/refractory MM."( Pharmacokinetics and safety of ixazomib plus lenalidomide-dexamethasone in Asian patients with relapsed/refractory myeloma: a phase 1 study.
Chim, CS; Chng, WJ; Esseltine, DL; Goh, YT; Gupta, N; Hanley, MJ; Hui, AM; Kim, K; Lee, JH; Min, CK; Venkatakrishnan, K; Wong, RS; Yang, H, 2015)		0.93
" The clinical drug-drug interaction study results were reconciled well by a physiologically based pharmacokinetic model that incorporated a minor contribution of CYP3A to overall ixazomib clearance and quantitatively considered the strength of induction of CYP3A and intestinal P-glycoprotein by rifampin."( Effects of Strong CYP3A Inhibition and Induction on the Pharmacokinetics of Ixazomib, an Oral Proteasome Inhibitor: Results of Drug-Drug Interaction Studies in Patients With Advanced Solid Tumors or Lymphoma and a Physiologically Based Pharmacokinetic Ana
Bessudo, A; Esseltine, DL; Gupta, N; Hanley, MJ; Ke, A; Liu, G; Nemunaitis, J; O'Neil, BH; Patel, C; Rasco, DW; Rowland Yeo, K; Sharma, S; Venkatakrishnan, K; Wang, B; Xia, C; Zhang, X, 2018)		0.9

Compound-Compound Interactions

Ixazomib is an oral proteasome inhibitor (PI) used in combination with lenalidomide and dexamethasone (IXA-Rd) for patients with relapsed and/or refractory multiple myeloma (RRMM) Previous studies investigating the safety and efficacy of ICD in patients with RRMM demonstrate a toxicity profile.

ExcerptReferenceRelevance
" Together, our data suggest the potential for proteasome inhibitor based therapy in CLL and the rationale design of drug combination strategies based on CLL biology."( The investigational agent MLN2238 induces apoptosis and is cytotoxic to CLL cells in vitro, as a single agent and in combination with other drugs.
Advani, P; Akhtar, D; Chanan-Khan, A; Chitta, K; Colon-Otero, G; Foran, J; Khan, AN; Masood, A; Miller, KC; Paulus, A; Rivera, C; Roy, V, 2014)		0.4
" In a phase 1/2 trial we aimed to assess the safety, tolerability, and activity of ixazomib in combination with lenalidomide and dexamethasone in newly diagnosed multiple myeloma."( Safety and tolerability of ixazomib, an oral proteasome inhibitor, in combination with lenalidomide and dexamethasone in patients with previously untreated multiple myeloma: an open-label phase 1/2 study.
Berdeja, JG; Berg, D; Di Bacco, A; Estevam, J; Gupta, N; Hamadani, M; Hari, P; Hui, AM; Kaufman, JL; Kumar, SK; Laubach, JP; Liao, E; Lonial, S; Niesvizky, R; Rajkumar, V; Richardson, PG; Roy, V; Stewart, AK; Vescio, R, 2014)		0.92
"We report the first clinical investigation conducted in Japan to confirm the safety, tolerability, and pharmacokinetics of ixazomib alone and combined with lenalidomide-dexamethasone (Rd) in Japanese patients with relapsed/refractory multiple myeloma."( Phase 1 study of ixazomib alone or combined with lenalidomide-dexamethasone in Japanese patients with relapsed/refractory multiple myeloma.
Chou, T; Handa, H; Ishizawa, K; Kase, Y; Suzuki, K; Takubo, T, 2017)		1
" Eighty-eight patients were enrolled across the 3 drug-drug interaction studies; the ixazomib toxicity profile was consistent with previous studies."( Effects of Strong CYP3A Inhibition and Induction on the Pharmacokinetics of Ixazomib, an Oral Proteasome Inhibitor: Results of Drug-Drug Interaction Studies in Patients With Advanced Solid Tumors or Lymphoma and a Physiologically Based Pharmacokinetic Ana
Bessudo, A; Esseltine, DL; Gupta, N; Hanley, MJ; Ke, A; Liu, G; Nemunaitis, J; O'Neil, BH; Patel, C; Rasco, DW; Rowland Yeo, K; Sharma, S; Venkatakrishnan, K; Wang, B; Xia, C; Zhang, X, 2018)		0.93
" In a preclinical study TNBC cells were treated with the first-generation proteasome inhibitor bortezomib in combination with cisplatin and synergistic efficacy was demonstrated."( Ixazomib in combination with carboplatin in pretreated women with advanced triple-negative breast cancer, a phase I/II trial of the AGMT (AGMT MBC-10 trial).
Balic, M; Bartsch, R; Burgstaller, S; Egle, D; Fuchs, D; Gampenrieder, SP; Greil, R; Melchardt, T; Mlineritsch, B; Petru, E; Petzer, A; Rinnerthaler, G; Rossmann, D; Rumpold, H; Singer, CF; Ulmer, H, 2018)		1.92
" Patients will receive ixazomib in combination with carboplatin on days 1, 8, and 15 in a 28-day cycle."( Ixazomib in combination with carboplatin in pretreated women with advanced triple-negative breast cancer, a phase I/II trial of the AGMT (AGMT MBC-10 trial).
Balic, M; Bartsch, R; Burgstaller, S; Egle, D; Fuchs, D; Gampenrieder, SP; Greil, R; Melchardt, T; Mlineritsch, B; Petru, E; Petzer, A; Rinnerthaler, G; Rossmann, D; Rumpold, H; Singer, CF; Ulmer, H, 2018)		2.23
" A phase I trial of the second-generation proteasome inhibitor ixazomib in combination with MEC (mitoxantrone, etoposide, and cytarabine) was conducted in patients with R/R AML."( A Phase I/II Trial of MEC (Mitoxantrone, Etoposide, Cytarabine) in Combination with Ixazomib for Relapsed Refractory Acute Myeloid Leukemia.
Advani, AS; Caimi, P; Carew, J; Carraway, H; Chan, R; Cooper, B; de Lima, M; Elson, P; Gerds, A; Hamilton, B; Kalaycio, M; Little, J; Maciejewski, J; Malek, E; Miron, A; Mukherjee, S; Nazha, A; Pink, J; Sekeres, MA; Sobecks, R; Tomlinson, B; Unger, A; Visconte, V; Wei, W, 2019)		0.98
" The combination of cyclophosphamide and dexamethasone (CD) is a recognised treatment option for patients with relapsed refractory multiple myeloma (RRMM) who have relapsed after treatment with bortezomib and lenalidomide, whilst also often being combined with newer proteasome inhibitors."( The MUK eight protocol: a randomised phase II trial of cyclophosphamide and dexamethasone in combination with ixazomib, in relapsed or refractory multiple myeloma (RRMM) patients who have relapsed after treatment with thalidomide, lenalidomide and a prote
Auner, HW; Bailey, L; Brown, S; Brudenell Straw, F; Cook, G; Cook, M; Dawkins, B; Flanagan, L; Hinsley, S; Kaiser, MF; McKee, S; Meads, D; Reed, S; Sherratt, D; Walker, K, 2020)		0.77
" The primary objective of the trial is to evaluate whether ixazomib in combination with cyclophosphamide and dexamethasone (ICD) has improved clinical activity compared to CD in terms of progression-free survival (PFS)."( The MUK eight protocol: a randomised phase II trial of cyclophosphamide and dexamethasone in combination with ixazomib, in relapsed or refractory multiple myeloma (RRMM) patients who have relapsed after treatment with thalidomide, lenalidomide and a prote
Auner, HW; Bailey, L; Brown, S; Brudenell Straw, F; Cook, G; Cook, M; Dawkins, B; Flanagan, L; Hinsley, S; Kaiser, MF; McKee, S; Meads, D; Reed, S; Sherratt, D; Walker, K, 2020)		1.01
" Previous studies investigating the safety and efficacy of ICD in patients with RRMM demonstrate a toxicity profile consistent with ixazomib in combination with lenalidomide and dexamethasone, whilst the combination showed possible activity in RRMM patients."( The MUK eight protocol: a randomised phase II trial of cyclophosphamide and dexamethasone in combination with ixazomib, in relapsed or refractory multiple myeloma (RRMM) patients who have relapsed after treatment with thalidomide, lenalidomide and a prote
Auner, HW; Bailey, L; Brown, S; Brudenell Straw, F; Cook, G; Cook, M; Dawkins, B; Flanagan, L; Hinsley, S; Kaiser, MF; McKee, S; Meads, D; Reed, S; Sherratt, D; Walker, K, 2020)		0.97
" In this study, we used a cardiomyocyte model to investigate the molecular cardiotoxic mechanisms of carfilzomib (CFZ) and ixazomib (IXZ) alone or in combination with the immunomodulatory drug dexamethasone (DEX) which is frequently used in combination therapies in the clinic."( Molecular Cardiotoxic Effects of Proteasome Inhibitors Carfilzomib and Ixazomib and Their Combination with Dexamethasone Involve Mitochondrial Dysregulation.
Alpertunga, B; Arslan Eseryel, S; Gunaydin Akyildiz, A; Jannuzzi, AT; Karademir Yilmaz, B; Korkmaz, NS, 2023)		1.35
"Ixazomib (IXA) is an oral proteasome inhibitor (PI) used in combination with lenalidomide and dexamethasone (IXA-Rd) for patients with relapsed and/or refractory multiple myeloma (RRMM)."( Real-world effectiveness of ixazomib combined with lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: the REMIX study.
Barrak, J; Benboubker, L; Calmettes, C; Charvet-Rumpler, A; Chouaid, C; Clement-Filliatre, L; Honeyman, F; Hulin, C; Karlin, L; Laribi, K; Leleu, X; Macro, M; Maloisel, F; Richez, V; Stoppa, AM; Vincent, L; Zerazhi, H, 2023)		2.65

Bioavailability

Model-informed drug development (MIDD) was central to the development of the oral proteasome inhibitor ixazomib, facilitating internal decisions. Many recent studies have investigated the safety of orally bioavailable prote asome inhibitors, such as ix Razomib and oprozomib. IxazomIB is an orally bio available proteasomesome inhibitor with a rapid proteasomal dissociation rate.

ExcerptReferenceRelevance
"MLN9708 (ixazomib citrate) is an investigational, orally bioavailable proteasome inhibitor that is under development by Millennium in clinical studies in both hematologic and nonhematologic malignancies."( Syntheses of C-13 and C-14-labeled versions of the investigational proteasome inhibitor MLN9708.
Elliott, EL; Li, Y; Plesescu, M; Prakash, SR, )		0.55
" Ixazomib is an investigational, orally bioavailable 20S proteasome inhibitor."( Phase 1 study of weekly dosing with the investigational oral proteasome inhibitor ixazomib in relapsed/refractory multiple myeloma.
Bensinger, WI; Berenson, JR; Berg, D; Di Bacco, A; Gupta, N; Hui, AM; Kumar, SK; Niesvizky, R; Reeder, CB; Shou, Y; Yu, J; Zimmerman, TM, 2014)		1.54
" Estimated absolute bioavailability and clearance were 60% and 2l h(-1), respectively."( Switching from body surface area-based to fixed dosing for the investigational proteasome inhibitor ixazomib: a population pharmacokinetic analysis.
Esseltine, DL; Gupta, N; Hui, AM; Venkatakrishnan, K; Zhao, Y, 2015)		0.63
"This phase 2 trial was designed to evaluate ixazomib, an orally bioavailable proteasome inhibitor, in patients with myeloma who have limited prior exposure to bortezomib."( Phase 2 trial of ixazomib in patients with relapsed multiple myeloma not refractory to bortezomib.
Bergsagel, PL; Buadi, FK; Chanan-Khan, A; Dispenzieri, A; Fonseca, R; Gertz, MA; Hwa, L; Kapoor, P; Kumar, SK; Lacy, MQ; LaPlant, B; Laumann, K; Mikhael, JR; Rajkumar, SV; Reeder, CB; Rivera, CE; Roy, V; Stewart, AK; Thompson, MA; Witzig, TE, 2015)		1.02
" The unsuccessful clinical trials of proteasome inhibitor PS-341 (bortezomib) in solid tumors led to the invention of MLN9708 (ixazomib), an orally bioavailable next-generation proteasome inhibitor with improved pharmacokinetic and pharmacodynamic features."( Next-generation proteasome inhibitor MLN9708 sensitizes breast cancer cells to doxorubicin-induced apoptosis.
Cao, WM; Cui, Y; Dou, J; Jiang, Z; Wang, H; Wang, Z; Yu, Y; Zhang, H; Zhao, Y, 2016)		0.64
" We chose ixazomib, an orally bioavailable proteasome inhibitor, because of its favorable physiochemical characteristics."( Post-Transplantation Cyclophosphamide and Ixazomib Combination Rescues Mice Subjected to Experimental Graft-versus-Host Disease and Is Superior to Either Agent Alone.
Abdel-Mageed, S; Al-Homsi, AS; Cole, K; Feng, Y; Goodyke, A; McLane, M; Muilenburg, M, 2017)		1.12
" Ixazomib is an orally bioavailable proteasome inhibitor with a rapid proteasome dissociation rate."( Ixazomib suppresses human dendritic cell and modulates murine graft-versus-host disease in a schedule-dependent fashion.
Abdel-Mageed, S; Al-Homsi, AS; Cole, K; Feng, Y; Goodyke, A; McLane, M; Muilenburg, M, 2017)		2.81
" Many recent studies have investigated the safety of orally bioavailable proteasome inhibitors, such as ixazomib and oprozomib."( Proteasome inhibitor-induced gastrointestinal toxicity.
Gibson, RJ; Stansborough, RL, 2017)		0.67
"gov identifier NCT01454076) assessed the relative bioavailability of capsule B in reference to capsule A in adult patients with advanced solid tumors or lymphoma."( A Phase 1 Study to Assess the Relative Bioavailability of Two Capsule Formulations of Ixazomib, an Oral Proteasome Inhibitor, in Patients With Advanced Solid Tumors or Lymphoma.
Bessudo, A; Gupta, N; Hanley, MJ; Nemunaitis, J; O'Neil, BH; Sharma, S; van de Velde, H; Venkatakrishnan, K; Wang, B, 2018)		0.7
" The orally bioavailable proteasome inhibitor MLN2238 (ixazomib) has been demonstrated to have anticancer activity."( Preclinical evaluation of antitumor activity of the proteasome inhibitor MLN2238 (ixazomib) in hepatocellular carcinoma cells.
Augello, G; Azzolina, A; Cassata, G; Cervello, M; Cusimano, A; Di Sano, C; Emma, MR; Modica, M; Montalto, G; Puleio, R, 2018)		0.95
"Model-informed drug development (MIDD) was central to the development of the oral proteasome inhibitor ixazomib, facilitating internal decisions (switch from body surface area (BSA)-based to fixed dosing, inclusive phase III trials, portfolio prioritization of ixazomib-based combinations, phase III dose for maintenance treatment), regulatory review (model-informed QT analysis, benefit-risk of 4 mg dose), and product labeling (absolute bioavailability and intrinsic/extrinsic factors)."( Model-Informed Drug Development for Ixazomib, an Oral Proteasome Inhibitor.
Berg, D; Diderichsen, PM; Gupta, N; Hanley, MJ; Ke, A; Labotka, R; Liu, G; Patel, C; Teng, Z; van de Velde, H; Venkatakrishnan, K; Yang, H, 2019)		1
"5 days) with first-order linear absorption (oral bioavailability of 58%)."( Clinical Pharmacology of Ixazomib: The First Oral Proteasome Inhibitor.
Gupta, N; Hanley, MJ; Harvey, RD; Labotka, R; Venkatakrishnan, K; Xia, C, 2019)		0.82
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019)		0.51

Dosage Studied

This analysis supports a switch from BSA-based to fixed dosing, without dose modification for mild/moderate renal impairment or age. Ixazomib is ideally suited for maintenance therapy given its convenient once-weekly oral dosing and low toxicity profile.

ExcerptRelevanceReference
" Moreover, antitumor activity was shown via multiple dosing routes, including oral gavage."( Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer.
Bannerman, B; Berger, A; Blank, J; Bolen, J; Bruzzese, F; Cao, Y; Dick, L; Fitzgerald, M; Fleming, P; Garcia, K; Hales, P; Kupperman, E; Lee, EC; Liu, J; Manfredi, M; Rolfe, M; Tsu, C; Yang, Y; Yu, J; Yu, L, 2010)		0.36
"Data were pooled from 226 adult patients with multiple myeloma, lymphoma or solid tumours in four phase 1 studies, in which ixazomib dosing (oral/intravenous, once/twice weekly) was based on BSA."( Switching from body surface area-based to fixed dosing for the investigational proteasome inhibitor ixazomib: a population pharmacokinetic analysis.
Esseltine, DL; Gupta, N; Hui, AM; Venkatakrishnan, K; Zhao, Y, 2015)		0.84
"23 mg m(-2)) and fixed (4 mg) oral dosing with no trend in simulated AUC vs."( Switching from body surface area-based to fixed dosing for the investigational proteasome inhibitor ixazomib: a population pharmacokinetic analysis.
Esseltine, DL; Gupta, N; Hui, AM; Venkatakrishnan, K; Zhao, Y, 2015)		0.63
"This analysis supports a switch from BSA-based to fixed dosing, without dose modification for mild/moderate renal impairment or age, in future adult studies of ixazomib, simplifying dosing guidance and clinical development."( Switching from body surface area-based to fixed dosing for the investigational proteasome inhibitor ixazomib: a population pharmacokinetic analysis.
Esseltine, DL; Gupta, N; Hui, AM; Venkatakrishnan, K; Zhao, Y, 2015)		0.83
" The current analysis characterized the exposure-safety and exposure-efficacy relationships of ixazomib in patients with relapsed/refractory multiple myeloma (MM) with a purpose of recommending an approach to ixazomib dosing for maintenance therapy."( Exposure-safety-efficacy analysis of single-agent ixazomib, an oral proteasome inhibitor, in relapsed/refractory multiple myeloma: dose selection for a phase 3 maintenance study.
Gupta, N; Hui, AM; Labotka, R; Liu, G; Venkatakrishnan, K, 2016)		0.91
" Areas covered: This review provides an overview of the (i) pharmacology and dosing of ixazomib, (ii) the efficacy and safety data from clinical studies, (iii) highlight the various novel combinations that have been reported, and (iv) give an overview of the ongoing studies with ixazomib."( Ixazomib: a novel drug for multiple myeloma.
Abeykoon, JP; Kapoor, P; Zanwar, S, 2018)		2.15
" The sensitivity of human colorectal carcinoma cells to the PI Ixazomib was assessed via in vitro and in vivo dose-response experiments."( Non-invasive imaging of disrupted protein homeostasis induced by proteasome inhibitor treatment using chemical exchange saturation transfer MRI.
Bradley, D; Chattopadhyay, N; Gibb, A; Golay, X; Johnson, SP; Lythgoe, MF; Pedley, RB; Ramasawmy, R; Taylor, V; Walker-Samuel, S; Zhu, Y, 2018)		0.72
" Ixazomib is ideally suited for maintenance therapy given its convenient once-weekly oral dosing and low toxicity profile."( Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial.
Beksac, M; Chng, WJ; Dash, AB; Dimopoulos, MA; Gay, F; Goldschmidt, H; Gupta, N; Hajek, R; Iida, S; Kaiser, M; Labotka, R; Maisnar, V; Mateos, MV; Min, CK; Moreau, P; Morgan, G; Palumbo, A; Pluta, A; Rajkumar, SV; Schjesvold, F; Skacel, T; Spencer, A; Suryanarayan, K; Teng, Z; Weisel, KC; Zweegman, S, 2019)		1.94
" B cell activating factor plasma levels were significantly higher after ixazomib dosing in those who remained cGVHD free compared with those developed cGVHD."( Ixazomib for Chronic Graft-versus-Host Disease Prophylaxis following Allogeneic Hematopoietic Cell Transplantation.
Abedin, S; Chhabra, S; D'Souza, A; Dhakal, B; Douglas Rizzo, J; Drobyski, WR; Fenske, TS; Hamadani, M; Hari, PN; Horowitz, MM; Jerkins, JH; Pasquini, MC; Runaas, L; Saber, W; Shah, NN; Shaw, BE; Tang, X; Thompson, R; Visotcky, A; Zhang, MJ; Zhu, F, 2020)		2.23
" Here, we investigated the safety and effectiveness of ixazomib dosing schedules."( Safety and Effectiveness of Ixazomib Dose-escalating Strategy in Ixazomib-Lenalidomide-Dexamethasone Treatment for Relapsed/Refractory Multiple Myeloma.
Boku, S; Higai, K; Kagoo, T; Niijima, D; Ogawa, C; Ohashi, Y; Tani, K; Ueno, H; Yachi, Y; Yano, T; Yatabe, M; Yokoyama, A, )		0.67
"A dose-escalation strategy to optimise ixazomib dosing may reduce treatment interruption due to adverse events without compromising its antitumor activity."( Safety and Effectiveness of Ixazomib Dose-escalating Strategy in Ixazomib-Lenalidomide-Dexamethasone Treatment for Relapsed/Refractory Multiple Myeloma.
Boku, S; Higai, K; Kagoo, T; Niijima, D; Ogawa, C; Ohashi, Y; Tani, K; Ueno, H; Yachi, Y; Yano, T; Yatabe, M; Yokoyama, A, )		0.69
" The developed framework represents an integrated approach to describing safety and efficacy with MM therapy, enabling the simulation of prospective trials and potential alternate dosing regimens."( Population pharmacokinetic/pharmacodynamic joint modeling of ixazomib efficacy and safety using data from the pivotal phase III TOURMALINE-MM1 study in multiple myeloma patients.
Diderichsen, PM; Gupta, N; Hanley, MJ; Labotka, R; Srimani, JK; Venkatakrishnan, K, 2022)		0.96
"We evaluated the safety and efficacy of the all-oral regimen of ixazomib, cyclophosphamide, and dexamethasone with the use of metronomic cyclophosphamide dosing in the treatment of patients with newly diagnosed multiple myeloma."( Ixazomib, Oral Metronomic Cyclophosphamide, and Dexamethasone for First-Line Treatment of Multiple Myeloma: A Phase II Brown University Oncology Group Study.
Barth, P; Olszewski, AJ; Pelcovits, A; Reagan, JL; Rosati, V; Sturtevant, A; Winer, ES; Wood, R, 2023)		2.59
" Collectively, these results highlight the value of safety-driven personalized dosing to maximize patient benefit/risk."( Dose Titration of Ixazomib Maintenance Therapy in Transplant-Ineligible Multiple Myeloma: Exposure-Response Analysis of the TOURMALINE-MM4 Study.
Diderichsen, PM; Gupta, N; Hanley, MJ; Labotka, R; Srimani, JK, 2023)		1.24
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (5)

RoleDescription
apoptosis inducerAny substance that induces the process of apoptosis (programmed cell death) in multi-celled organisms.
orphan drugAny drug that has been developed specifically for treatment of a rare medical condition, the condition itself being known as an orphan disease.
proteasome inhibitorA drug that blocks the action of proteasomes, cellular complexes that break down proteins.
drug metabolitenull
antineoplastic agentA substance that inhibits or prevents the proliferation of neoplasms.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (4)

ClassDescription
benzamides
dichlorobenzeneAny member of the class of chlorobenzenes carrying two chloro groups at unspecified positions.
glycine derivativeA proteinogenic amino acid derivative resulting from reaction of glycine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
boronic acidsCompounds having the structure RB(OH)2.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (26)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Fumarate hydrataseHomo sapiens (human)Potency0.41760.00308.794948.0869AID1347053
PPM1D proteinHomo sapiens (human)Potency0.10440.00529.466132.9993AID1347411
EWS/FLI fusion proteinHomo sapiens (human)Potency0.30300.001310.157742.8575AID1259252; AID1259253; AID1259255; AID1259256
polyproteinZika virusPotency0.41760.00308.794948.0869AID1347053
Interferon betaHomo sapiens (human)Potency0.10440.00339.158239.8107AID1347411
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Proteasome subunit beta type-11Homo sapiens (human)IC50 (µMol)0.01500.00130.70995.0000AID1559513
Proteasome subunit alpha type-7Homo sapiens (human)IC50 (µMol)0.01500.00130.70995.0000AID1559513
Proteasome subunit beta type-1Homo sapiens (human)IC50 (µMol)0.01630.00060.73766.3700AID1559513; AID1604182; AID706736
Proteasome subunit alpha type-1Homo sapiens (human)IC50 (µMol)0.01500.00130.70995.0000AID1559513
Proteasome subunit alpha type-2Homo sapiens (human)IC50 (µMol)0.01500.00130.70995.0000AID1559513
Proteasome subunit alpha type-3Homo sapiens (human)IC50 (µMol)0.01500.00130.70995.0000AID1559513
Proteasome subunit alpha type-4Homo sapiens (human)IC50 (µMol)0.01500.00130.70995.0000AID1559513
Proteasome subunit beta type-8Homo sapiens (human)IC50 (µMol)0.01500.00130.36985.0000AID1559513
Proteasome subunit beta type-9Homo sapiens (human)IC50 (µMol)0.01500.00100.76115.0000AID1559513
Proteasome subunit alpha type-5Homo sapiens (human)IC50 (µMol)0.01500.00130.70995.0000AID1559513
Proteasome subunit beta type-4Homo sapiens (human)IC50 (µMol)0.01500.00130.70995.0000AID1559513
Proteasome subunit beta type-6Homo sapiens (human)IC50 (µMol)0.01500.00130.69125.0000AID1559513
Proteasome subunit beta type-5Homo sapiens (human)IC50 (µMol)0.00650.00050.939410.0000AID1396601; AID1559513; AID1604186; AID1864383; AID706738
Proteasome subunit beta type-10Homo sapiens (human)IC50 (µMol)0.01500.00130.81515.0000AID1559513
Proteasome subunit beta type-3Homo sapiens (human)IC50 (µMol)0.01500.00130.70995.0000AID1559513
Proteasome subunit beta type-2Homo sapiens (human)IC50 (µMol)1.18170.00131.39067.9540AID1559513; AID1604184; AID706737
Proteasome subunit alpha type-6Homo sapiens (human)IC50 (µMol)0.01500.00130.70995.0000AID1559513
ATP-dependent Clp protease proteolytic subunitStaphylococcus aureus subsp. aureus NCTC 8325IC50 (µMol)5.30005.30005.30005.3000AID1605096
NACHT, LRR and PYD domains-containing protein 3 Mus musculus (house mouse)IC50 (µMol)0.19950.00041.441910.0000AID1864382
Proteasome subunit alpha-type 8Homo sapiens (human)IC50 (µMol)0.01500.00130.70995.0000AID1559513
Proteasome subunit beta type-7Homo sapiens (human)IC50 (µMol)0.01500.00130.68435.0000AID1559513
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Activation Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
ATP-dependent Clp protease proteolytic subunitStaphylococcus aureus subsp. aureus NCTC 8325EC50 (µMol)3.60003.60003.60003.6000AID1605098
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (53)

Processvia Protein(s)Taxonomy
proteolysisProteasome subunit beta type-11Homo sapiens (human)
T cell differentiation in thymusProteasome subunit beta type-11Homo sapiens (human)
CD8-positive, alpha-beta T cell differentiationProteasome subunit beta type-11Homo sapiens (human)
proteasome-mediated ubiquitin-dependent protein catabolic processProteasome subunit beta type-11Homo sapiens (human)
proteasome-mediated ubiquitin-dependent protein catabolic processProteasome subunit alpha type-7Homo sapiens (human)
cell surface receptor signaling pathway via JAK-STATInterferon betaHomo sapiens (human)
response to exogenous dsRNAInterferon betaHomo sapiens (human)
B cell activation involved in immune responseInterferon betaHomo sapiens (human)
cell surface receptor signaling pathwayInterferon betaHomo sapiens (human)
cell surface receptor signaling pathway via JAK-STATInterferon betaHomo sapiens (human)
response to virusInterferon betaHomo sapiens (human)
positive regulation of autophagyInterferon betaHomo sapiens (human)
cytokine-mediated signaling pathwayInterferon betaHomo sapiens (human)
natural killer cell activationInterferon betaHomo sapiens (human)
positive regulation of peptidyl-serine phosphorylation of STAT proteinInterferon betaHomo sapiens (human)
cellular response to interferon-betaInterferon betaHomo sapiens (human)
B cell proliferationInterferon betaHomo sapiens (human)
negative regulation of viral genome replicationInterferon betaHomo sapiens (human)
innate immune responseInterferon betaHomo sapiens (human)
positive regulation of innate immune responseInterferon betaHomo sapiens (human)
regulation of MHC class I biosynthetic processInterferon betaHomo sapiens (human)
negative regulation of T cell differentiationInterferon betaHomo sapiens (human)
positive regulation of transcription by RNA polymerase IIInterferon betaHomo sapiens (human)
defense response to virusInterferon betaHomo sapiens (human)
type I interferon-mediated signaling pathwayInterferon betaHomo sapiens (human)
neuron cellular homeostasisInterferon betaHomo sapiens (human)
cellular response to exogenous dsRNAInterferon betaHomo sapiens (human)
cellular response to virusInterferon betaHomo sapiens (human)
negative regulation of Lewy body formationInterferon betaHomo sapiens (human)
negative regulation of T-helper 2 cell cytokine productionInterferon betaHomo sapiens (human)
positive regulation of apoptotic signaling pathwayInterferon betaHomo sapiens (human)
response to exogenous dsRNAInterferon betaHomo sapiens (human)
B cell differentiationInterferon betaHomo sapiens (human)
natural killer cell activation involved in immune responseInterferon betaHomo sapiens (human)
adaptive immune responseInterferon betaHomo sapiens (human)
T cell activation involved in immune responseInterferon betaHomo sapiens (human)
humoral immune responseInterferon betaHomo sapiens (human)
proteasome-mediated ubiquitin-dependent protein catabolic processProteasome subunit beta type-1Homo sapiens (human)
proteolysis involved in protein catabolic processProteasome subunit beta type-1Homo sapiens (human)
immune system processProteasome subunit alpha type-1Homo sapiens (human)
negative regulation of inflammatory response to antigenic stimulusProteasome subunit alpha type-1Homo sapiens (human)
proteasome-mediated ubiquitin-dependent protein catabolic processProteasome subunit alpha type-1Homo sapiens (human)
response to virusProteasome subunit alpha type-2Homo sapiens (human)
proteasome-mediated ubiquitin-dependent protein catabolic processProteasome subunit alpha type-2Homo sapiens (human)
proteasome-mediated ubiquitin-dependent protein catabolic processProteasome subunit alpha type-3Homo sapiens (human)
regulation of endopeptidase activityProteasome subunit alpha type-3Homo sapiens (human)
proteasome-mediated ubiquitin-dependent protein catabolic processProteasome subunit alpha type-4Homo sapiens (human)
antigen processing and presentationProteasome subunit beta type-8Homo sapiens (human)
fat cell differentiationProteasome subunit beta type-8Homo sapiens (human)
regulation of endopeptidase activityProteasome subunit beta type-8Homo sapiens (human)
proteasome-mediated ubiquitin-dependent protein catabolic processProteasome subunit beta type-8Homo sapiens (human)
immune system processProteasome subunit beta type-9Homo sapiens (human)
regulation of cysteine-type endopeptidase activityProteasome subunit beta type-9Homo sapiens (human)
proteasome-mediated ubiquitin-dependent protein catabolic processProteasome subunit beta type-9Homo sapiens (human)
proteasome-mediated ubiquitin-dependent protein catabolic processProteasome subunit alpha type-5Homo sapiens (human)
negative regulation of inflammatory response to antigenic stimulusProteasome subunit beta type-4Homo sapiens (human)
proteasome-mediated ubiquitin-dependent protein catabolic processProteasome subunit beta type-4Homo sapiens (human)
proteasome-mediated ubiquitin-dependent protein catabolic processProteasome subunit beta type-6Homo sapiens (human)
proteolysisProteasome subunit beta type-5Homo sapiens (human)
response to oxidative stressProteasome subunit beta type-5Homo sapiens (human)
proteasome-mediated ubiquitin-dependent protein catabolic processProteasome subunit beta type-5Homo sapiens (human)
cell morphogenesisProteasome subunit beta type-10Homo sapiens (human)
humoral immune responseProteasome subunit beta type-10Homo sapiens (human)
T cell proliferationProteasome subunit beta type-10Homo sapiens (human)
proteasome-mediated ubiquitin-dependent protein catabolic processProteasome subunit beta type-10Homo sapiens (human)
proteasome-mediated ubiquitin-dependent protein catabolic processProteasome subunit beta type-3Homo sapiens (human)
response to organonitrogen compoundProteasome subunit beta type-2Homo sapiens (human)
response to organic cyclic compoundProteasome subunit beta type-2Homo sapiens (human)
proteasome-mediated ubiquitin-dependent protein catabolic processProteasome subunit beta type-2Homo sapiens (human)
proteasome-mediated ubiquitin-dependent protein catabolic processProteasome subunit alpha type-6Homo sapiens (human)
regulation of inflammatory responseProteasome subunit alpha type-6Homo sapiens (human)
positive regulation of NF-kappaB transcription factor activityProteasome subunit alpha type-6Homo sapiens (human)
proteolysis involved in protein catabolic processProteasome subunit alpha type-6Homo sapiens (human)
spermatogenesisProteasome subunit alpha-type 8Homo sapiens (human)
proteasomal protein catabolic processProteasome subunit alpha-type 8Homo sapiens (human)
cell differentiationProteasome subunit alpha-type 8Homo sapiens (human)
meiotic cell cycleProteasome subunit alpha-type 8Homo sapiens (human)
regulation of meiosis IProteasome subunit alpha-type 8Homo sapiens (human)
proteasome-mediated ubiquitin-dependent protein catabolic processProteasome subunit alpha-type 8Homo sapiens (human)
proteasome-mediated ubiquitin-dependent protein catabolic processProteasome subunit beta type-7Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (15)

Processvia Protein(s)Taxonomy
threonine-type endopeptidase activityProteasome subunit beta type-11Homo sapiens (human)
protein bindingProteasome subunit beta type-11Homo sapiens (human)
peptidase activityProteasome subunit beta type-11Homo sapiens (human)
endopeptidase activityProteasome subunit beta type-11Homo sapiens (human)
protein bindingProteasome subunit alpha type-7Homo sapiens (human)
identical protein bindingProteasome subunit alpha type-7Homo sapiens (human)
cytokine activityInterferon betaHomo sapiens (human)
cytokine receptor bindingInterferon betaHomo sapiens (human)
type I interferon receptor bindingInterferon betaHomo sapiens (human)
protein bindingInterferon betaHomo sapiens (human)
chloramphenicol O-acetyltransferase activityInterferon betaHomo sapiens (human)
protein bindingProteasome subunit beta type-1Homo sapiens (human)
lipopolysaccharide bindingProteasome subunit alpha type-1Homo sapiens (human)
protein bindingProteasome subunit alpha type-1Homo sapiens (human)
protein bindingProteasome subunit alpha type-2Homo sapiens (human)
protein bindingProteasome subunit alpha type-3Homo sapiens (human)
ubiquitin protein ligase bindingProteasome subunit alpha type-3Homo sapiens (human)
protein bindingProteasome subunit alpha type-4Homo sapiens (human)
threonine-type endopeptidase activityProteasome subunit beta type-8Homo sapiens (human)
protein bindingProteasome subunit beta type-8Homo sapiens (human)
endopeptidase activityProteasome subunit beta type-8Homo sapiens (human)
threonine-type endopeptidase activityProteasome subunit beta type-9Homo sapiens (human)
protein bindingProteasome subunit beta type-9Homo sapiens (human)
endopeptidase activityProteasome subunit beta type-9Homo sapiens (human)
protein bindingProteasome subunit alpha type-5Homo sapiens (human)
lipopolysaccharide bindingProteasome subunit beta type-4Homo sapiens (human)
protein bindingProteasome subunit beta type-4Homo sapiens (human)
endopeptidase activityProteasome subunit beta type-6Homo sapiens (human)
threonine-type endopeptidase activityProteasome subunit beta type-6Homo sapiens (human)
protein bindingProteasome subunit beta type-6Homo sapiens (human)
cadherin bindingProteasome subunit beta type-6Homo sapiens (human)
threonine-type endopeptidase activityProteasome subunit beta type-5Homo sapiens (human)
protein bindingProteasome subunit beta type-5Homo sapiens (human)
peptidase activityProteasome subunit beta type-5Homo sapiens (human)
endopeptidase activityProteasome subunit beta type-5Homo sapiens (human)
threonine-type endopeptidase activityProteasome subunit beta type-10Homo sapiens (human)
protein bindingProteasome subunit beta type-10Homo sapiens (human)
endopeptidase activityProteasome subunit beta type-10Homo sapiens (human)
protein bindingProteasome subunit beta type-3Homo sapiens (human)
protein bindingProteasome subunit beta type-2Homo sapiens (human)
RNA bindingProteasome subunit alpha type-6Homo sapiens (human)
endopeptidase activityProteasome subunit alpha type-6Homo sapiens (human)
protein bindingProteasome subunit alpha type-6Homo sapiens (human)
purine ribonucleoside triphosphate bindingProteasome subunit alpha type-6Homo sapiens (human)
NF-kappaB bindingProteasome subunit alpha type-6Homo sapiens (human)
threonine-type endopeptidase activityProteasome subunit beta type-7Homo sapiens (human)
protein bindingProteasome subunit beta type-7Homo sapiens (human)
endopeptidase activityProteasome subunit beta type-7Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (27)

Processvia Protein(s)Taxonomy
cytosolProteasome subunit beta type-11Homo sapiens (human)
proteasome core complex, beta-subunit complexProteasome subunit beta type-11Homo sapiens (human)
nucleusProteasome subunit beta type-11Homo sapiens (human)
cytosolProteasome subunit beta type-11Homo sapiens (human)
nucleusProteasome subunit alpha type-7Homo sapiens (human)
cytoplasmProteasome subunit alpha type-7Homo sapiens (human)
proteasome complexProteasome subunit alpha type-7Homo sapiens (human)
nucleusProteasome subunit alpha type-7Homo sapiens (human)
nucleoplasmProteasome subunit alpha type-7Homo sapiens (human)
cytosolProteasome subunit alpha type-7Homo sapiens (human)
extracellular exosomeProteasome subunit alpha type-7Homo sapiens (human)
postsynapseProteasome subunit alpha type-7Homo sapiens (human)
proteasome core complexProteasome subunit alpha type-7Homo sapiens (human)
proteasome core complex, alpha-subunit complexProteasome subunit alpha type-7Homo sapiens (human)
extracellular spaceInterferon betaHomo sapiens (human)
extracellular regionInterferon betaHomo sapiens (human)
nucleusProteasome subunit beta type-1Homo sapiens (human)
cytoplasmProteasome subunit beta type-1Homo sapiens (human)
proteasome complexProteasome subunit beta type-1Homo sapiens (human)
extracellular regionProteasome subunit beta type-1Homo sapiens (human)
nucleusProteasome subunit beta type-1Homo sapiens (human)
nucleoplasmProteasome subunit beta type-1Homo sapiens (human)
cytosolProteasome subunit beta type-1Homo sapiens (human)
secretory granule lumenProteasome subunit beta type-1Homo sapiens (human)
extracellular exosomeProteasome subunit beta type-1Homo sapiens (human)
ficolin-1-rich granule lumenProteasome subunit beta type-1Homo sapiens (human)
proteasome core complexProteasome subunit beta type-1Homo sapiens (human)
proteasome core complex, beta-subunit complexProteasome subunit beta type-1Homo sapiens (human)
nucleusProteasome subunit alpha type-1Homo sapiens (human)
cytoplasmProteasome subunit alpha type-1Homo sapiens (human)
proteasome complexProteasome subunit alpha type-1Homo sapiens (human)
nucleusProteasome subunit alpha type-1Homo sapiens (human)
nucleoplasmProteasome subunit alpha type-1Homo sapiens (human)
centrosomeProteasome subunit alpha type-1Homo sapiens (human)
cytosolProteasome subunit alpha type-1Homo sapiens (human)
extracellular exosomeProteasome subunit alpha type-1Homo sapiens (human)
proteasome core complexProteasome subunit alpha type-1Homo sapiens (human)
proteasome core complex, alpha-subunit complexProteasome subunit alpha type-1Homo sapiens (human)
nucleusProteasome subunit alpha type-2Homo sapiens (human)
cytoplasmProteasome subunit alpha type-2Homo sapiens (human)
proteasome complexProteasome subunit alpha type-2Homo sapiens (human)
P-bodyProteasome subunit alpha type-2Homo sapiens (human)
extracellular regionProteasome subunit alpha type-2Homo sapiens (human)
nucleusProteasome subunit alpha type-2Homo sapiens (human)
nucleoplasmProteasome subunit alpha type-2Homo sapiens (human)
cytosolProteasome subunit alpha type-2Homo sapiens (human)
secretory granule lumenProteasome subunit alpha type-2Homo sapiens (human)
extracellular exosomeProteasome subunit alpha type-2Homo sapiens (human)
ficolin-1-rich granule lumenProteasome subunit alpha type-2Homo sapiens (human)
proteasome core complexProteasome subunit alpha type-2Homo sapiens (human)
proteasome core complex, alpha-subunit complexProteasome subunit alpha type-2Homo sapiens (human)
nucleusProteasome subunit alpha type-3Homo sapiens (human)
cytoplasmProteasome subunit alpha type-3Homo sapiens (human)
proteasome complexProteasome subunit alpha type-3Homo sapiens (human)
nucleusProteasome subunit alpha type-3Homo sapiens (human)
nucleoplasmProteasome subunit alpha type-3Homo sapiens (human)
cytoplasmProteasome subunit alpha type-3Homo sapiens (human)
cytosolProteasome subunit alpha type-3Homo sapiens (human)
extracellular exosomeProteasome subunit alpha type-3Homo sapiens (human)
proteasome core complexProteasome subunit alpha type-3Homo sapiens (human)
proteasome core complex, alpha-subunit complexProteasome subunit alpha type-3Homo sapiens (human)
synapseProteasome subunit alpha type-3Homo sapiens (human)
nucleusProteasome subunit alpha type-4Homo sapiens (human)
cytoplasmProteasome subunit alpha type-4Homo sapiens (human)
proteasome complexProteasome subunit alpha type-4Homo sapiens (human)
P-bodyProteasome subunit alpha type-4Homo sapiens (human)
nucleusProteasome subunit alpha type-4Homo sapiens (human)
nucleoplasmProteasome subunit alpha type-4Homo sapiens (human)
cytosolProteasome subunit alpha type-4Homo sapiens (human)
intracellular membrane-bounded organelleProteasome subunit alpha type-4Homo sapiens (human)
extracellular exosomeProteasome subunit alpha type-4Homo sapiens (human)
proteasome core complexProteasome subunit alpha type-4Homo sapiens (human)
proteasome core complex, alpha-subunit complexProteasome subunit alpha type-4Homo sapiens (human)
cytosolProteasome subunit alpha type-4Homo sapiens (human)
nucleoplasmProteasome subunit beta type-8Homo sapiens (human)
cytosolProteasome subunit beta type-8Homo sapiens (human)
extracellular exosomeProteasome subunit beta type-8Homo sapiens (human)
proteasome complexProteasome subunit beta type-8Homo sapiens (human)
proteasome core complexProteasome subunit beta type-8Homo sapiens (human)
proteasome core complex, beta-subunit complexProteasome subunit beta type-8Homo sapiens (human)
spermatoproteasome complexProteasome subunit beta type-8Homo sapiens (human)
nucleusProteasome subunit beta type-8Homo sapiens (human)
cytosolProteasome subunit beta type-8Homo sapiens (human)
nucleoplasmProteasome subunit beta type-9Homo sapiens (human)
cytosolProteasome subunit beta type-9Homo sapiens (human)
extracellular exosomeProteasome subunit beta type-9Homo sapiens (human)
proteasome complexProteasome subunit beta type-9Homo sapiens (human)
proteasome core complexProteasome subunit beta type-9Homo sapiens (human)
proteasome core complex, beta-subunit complexProteasome subunit beta type-9Homo sapiens (human)
spermatoproteasome complexProteasome subunit beta type-9Homo sapiens (human)
cytosolProteasome subunit beta type-9Homo sapiens (human)
nucleusProteasome subunit beta type-9Homo sapiens (human)
nucleusProteasome subunit alpha type-5Homo sapiens (human)
cytoplasmProteasome subunit alpha type-5Homo sapiens (human)
proteasome complexProteasome subunit alpha type-5Homo sapiens (human)
extracellular regionProteasome subunit alpha type-5Homo sapiens (human)
nucleusProteasome subunit alpha type-5Homo sapiens (human)
nucleoplasmProteasome subunit alpha type-5Homo sapiens (human)
cytosolProteasome subunit alpha type-5Homo sapiens (human)
secretory granule lumenProteasome subunit alpha type-5Homo sapiens (human)
extracellular exosomeProteasome subunit alpha type-5Homo sapiens (human)
ficolin-1-rich granule lumenProteasome subunit alpha type-5Homo sapiens (human)
proteasome core complexProteasome subunit alpha type-5Homo sapiens (human)
proteasome core complex, alpha-subunit complexProteasome subunit alpha type-5Homo sapiens (human)
nucleusProteasome subunit beta type-4Homo sapiens (human)
cytoplasmProteasome subunit beta type-4Homo sapiens (human)
proteasome complexProteasome subunit beta type-4Homo sapiens (human)
nucleusProteasome subunit beta type-4Homo sapiens (human)
nucleoplasmProteasome subunit beta type-4Homo sapiens (human)
mitochondrionProteasome subunit beta type-4Homo sapiens (human)
cytosolProteasome subunit beta type-4Homo sapiens (human)
ciliary basal bodyProteasome subunit beta type-4Homo sapiens (human)
extracellular exosomeProteasome subunit beta type-4Homo sapiens (human)
proteasome core complexProteasome subunit beta type-4Homo sapiens (human)
proteasome core complex, beta-subunit complexProteasome subunit beta type-4Homo sapiens (human)
cytosolProteasome subunit beta type-4Homo sapiens (human)
nucleusProteasome subunit beta type-6Homo sapiens (human)
cytoplasmProteasome subunit beta type-6Homo sapiens (human)
proteasome complexProteasome subunit beta type-6Homo sapiens (human)
nucleusProteasome subunit beta type-6Homo sapiens (human)
nucleoplasmProteasome subunit beta type-6Homo sapiens (human)
mitochondrionProteasome subunit beta type-6Homo sapiens (human)
cytosolProteasome subunit beta type-6Homo sapiens (human)
extracellular exosomeProteasome subunit beta type-6Homo sapiens (human)
proteasome core complexProteasome subunit beta type-6Homo sapiens (human)
proteasome core complex, beta-subunit complexProteasome subunit beta type-6Homo sapiens (human)
cytosolProteasome subunit beta type-6Homo sapiens (human)
nucleusProteasome subunit beta type-5Homo sapiens (human)
cytoplasmProteasome subunit beta type-5Homo sapiens (human)
proteasome complexProteasome subunit beta type-5Homo sapiens (human)
nucleusProteasome subunit beta type-5Homo sapiens (human)
nucleoplasmProteasome subunit beta type-5Homo sapiens (human)
centrosomeProteasome subunit beta type-5Homo sapiens (human)
cytosolProteasome subunit beta type-5Homo sapiens (human)
extracellular exosomeProteasome subunit beta type-5Homo sapiens (human)
proteasome core complexProteasome subunit beta type-5Homo sapiens (human)
proteasome core complex, beta-subunit complexProteasome subunit beta type-5Homo sapiens (human)
cytosolProteasome subunit beta type-5Homo sapiens (human)
nucleoplasmProteasome subunit beta type-10Homo sapiens (human)
cytosolProteasome subunit beta type-10Homo sapiens (human)
proteasome complexProteasome subunit beta type-10Homo sapiens (human)
proteasome core complexProteasome subunit beta type-10Homo sapiens (human)
proteasome core complex, beta-subunit complexProteasome subunit beta type-10Homo sapiens (human)
spermatoproteasome complexProteasome subunit beta type-10Homo sapiens (human)
cytosolProteasome subunit beta type-10Homo sapiens (human)
nucleusProteasome subunit beta type-10Homo sapiens (human)
nucleusProteasome subunit beta type-3Homo sapiens (human)
cytoplasmProteasome subunit beta type-3Homo sapiens (human)
proteasome complexProteasome subunit beta type-3Homo sapiens (human)
nucleusProteasome subunit beta type-3Homo sapiens (human)
nucleoplasmProteasome subunit beta type-3Homo sapiens (human)
cytosolProteasome subunit beta type-3Homo sapiens (human)
extracellular exosomeProteasome subunit beta type-3Homo sapiens (human)
proteasome core complexProteasome subunit beta type-3Homo sapiens (human)
proteasome core complex, beta-subunit complexProteasome subunit beta type-3Homo sapiens (human)
cytosolProteasome subunit beta type-3Homo sapiens (human)
nucleusProteasome subunit beta type-2Homo sapiens (human)
cytoplasmProteasome subunit beta type-2Homo sapiens (human)
proteasome complexProteasome subunit beta type-2Homo sapiens (human)
nucleusProteasome subunit beta type-2Homo sapiens (human)
nucleoplasmProteasome subunit beta type-2Homo sapiens (human)
cytosolProteasome subunit beta type-2Homo sapiens (human)
membraneProteasome subunit beta type-2Homo sapiens (human)
extracellular exosomeProteasome subunit beta type-2Homo sapiens (human)
proteasome core complexProteasome subunit beta type-2Homo sapiens (human)
proteasome core complex, beta-subunit complexProteasome subunit beta type-2Homo sapiens (human)
cytosolProteasome subunit beta type-2Homo sapiens (human)
nucleusProteasome subunit alpha type-6Homo sapiens (human)
cytoplasmProteasome subunit alpha type-6Homo sapiens (human)
proteasome complexProteasome subunit alpha type-6Homo sapiens (human)
P-bodyProteasome subunit alpha type-6Homo sapiens (human)
nucleusProteasome subunit alpha type-6Homo sapiens (human)
nucleoplasmProteasome subunit alpha type-6Homo sapiens (human)
cytosolProteasome subunit alpha type-6Homo sapiens (human)
ribosomeProteasome subunit alpha type-6Homo sapiens (human)
nuclear matrixProteasome subunit alpha type-6Homo sapiens (human)
myofibrilProteasome subunit alpha type-6Homo sapiens (human)
sarcomereProteasome subunit alpha type-6Homo sapiens (human)
extracellular exosomeProteasome subunit alpha type-6Homo sapiens (human)
proteasome core complexProteasome subunit alpha type-6Homo sapiens (human)
proteasome core complex, alpha-subunit complexProteasome subunit alpha type-6Homo sapiens (human)
cytosolNACHT, LRR and PYD domains-containing protein 3 Mus musculus (house mouse)
nucleusProteasome subunit alpha-type 8Homo sapiens (human)
cytosolProteasome subunit alpha-type 8Homo sapiens (human)
extracellular exosomeProteasome subunit alpha-type 8Homo sapiens (human)
proteasome core complex, alpha-subunit complexProteasome subunit alpha-type 8Homo sapiens (human)
spermatoproteasome complexProteasome subunit alpha-type 8Homo sapiens (human)
nucleusProteasome subunit alpha-type 8Homo sapiens (human)
nucleusProteasome subunit beta type-7Homo sapiens (human)
cytoplasmProteasome subunit beta type-7Homo sapiens (human)
proteasome complexProteasome subunit beta type-7Homo sapiens (human)
extracellular regionProteasome subunit beta type-7Homo sapiens (human)
nucleusProteasome subunit beta type-7Homo sapiens (human)
nucleoplasmProteasome subunit beta type-7Homo sapiens (human)
cytosolProteasome subunit beta type-7Homo sapiens (human)
nuclear bodyProteasome subunit beta type-7Homo sapiens (human)
secretory granule lumenProteasome subunit beta type-7Homo sapiens (human)
ficolin-1-rich granule lumenProteasome subunit beta type-7Homo sapiens (human)
proteasome core complexProteasome subunit beta type-7Homo sapiens (human)
proteasome core complex, beta-subunit complexProteasome subunit beta type-7Homo sapiens (human)
cytosolProteasome subunit beta type-7Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (78)

Assay IDTitleYearJournalArticle
AID1604184Inhibition of 20S proteasome beta 2c (unknown origin) after 1 hr by fluorescence based assay2019European journal of medicinal chemistry, Nov-15, Volume: 182Immunoproteasome-selective inhibitors: An overview of recent developments as potential drugs for hematologic malignancies and autoimmune diseases.
AID706738Reversible inhibition of human erythrocyte derived 20S proteasome subunit beta5 after 30 mins by fluorogenic assay2012Journal of medicinal chemistry, Dec-13, Volume: 55, Issue:23
Molecular mechanisms of acquired proteasome inhibitor resistance.
AID1396604Cytotoxicity against human RPMI8226 cells assessed as reduction in cell viability after 72 hrs by CellTiter 96 aqueous one solution assay2018Bioorganic & medicinal chemistry, 08-07, Volume: 26, Issue:14
Design, synthesis, in vitro and in vivo evaluation, and structure-activity relationship (SAR) discussion of novel dipeptidyl boronic acid proteasome inhibitors as orally available anti-cancer agents for the treatment of multiple myeloma and mechanism stud
AID1864383Inhibition of 20S proteasome beta5 subunit (unknown origin) using Suc-LLVY-AMC as flurogenic substrate measured after 1 hr by fluorescence based analysis2022Journal of medicinal chemistry, 09-22, Volume: 65, Issue:18
Discovery of a Novel Oral Proteasome Inhibitor to Block NLRP3 Inflammasome Activation with Anti-inflammation Activity.
AID1605096Inhibition of N-terminal His6-sumo-tagged full length Staphylococcus aureus ClpP expressed in Escherichia coli BL2 (DE3) pre-incubated for 10 mins before Suc-LY-AMC addition and measured after 1 hr by fluorescence based assay2020Journal of medicinal chemistry, 03-26, Volume: 63, Issue:6
Discovery of Novel Peptidomimetic Boronate ClpP Inhibitors with Noncanonical Enzyme Mechanism as Potent Virulence Blockers
AID1605100Cytotoxicity in human HeLa cells assessed as reduction in cell viability incubated for 24 hrs by MTT assay2020Journal of medicinal chemistry, 03-26, Volume: 63, Issue:6
Discovery of Novel Peptidomimetic Boronate ClpP Inhibitors with Noncanonical Enzyme Mechanism as Potent Virulence Blockers
AID1864429Inhibition of NLRP3 inflammasome activation in LPS-primed mouse J774.A1 cells assessed as reduction in IL-1beta secretion at 1 uM relative to control2022Journal of medicinal chemistry, 09-22, Volume: 65, Issue:18
Discovery of a Novel Oral Proteasome Inhibitor to Block NLRP3 Inflammasome Activation with Anti-inflammation Activity.
AID1396605Cytotoxicity against human U266B1 cells assessed as reduction in cell viability after 72 hrs by CellTiter 96 aqueous one solution assay2018Bioorganic & medicinal chemistry, 08-07, Volume: 26, Issue:14
Design, synthesis, in vitro and in vivo evaluation, and structure-activity relationship (SAR) discussion of novel dipeptidyl boronic acid proteasome inhibitors as orally available anti-cancer agents for the treatment of multiple myeloma and mechanism stud
AID1605101Cytotoxicity in human HepG2 cells assessed as reduction in cell viability incubated for 24 hrs by MTT assay2020Journal of medicinal chemistry, 03-26, Volume: 63, Issue:6
Discovery of Novel Peptidomimetic Boronate ClpP Inhibitors with Noncanonical Enzyme Mechanism as Potent Virulence Blockers
AID1605097Inhibition of N-terminal His6-sumo-tagged full length Staphylococcus aureus ClpP expressed in Escherichia coli BL2 (DE3) assessed as Kinact/Ki ratio pre-incubated for 10 mins before Suc-LY-AMC addition and measured after 1 hr by fluorescence based assay2020Journal of medicinal chemistry, 03-26, Volume: 63, Issue:6
Discovery of Novel Peptidomimetic Boronate ClpP Inhibitors with Noncanonical Enzyme Mechanism as Potent Virulence Blockers
AID1396606Cytotoxicity against human ARH77 cells assessed as reduction in cell viability after 72 hrs by CellTiter 96 aqueous one solution assay2018Bioorganic & medicinal chemistry, 08-07, Volume: 26, Issue:14
Design, synthesis, in vitro and in vivo evaluation, and structure-activity relationship (SAR) discussion of novel dipeptidyl boronic acid proteasome inhibitors as orally available anti-cancer agents for the treatment of multiple myeloma and mechanism stud
AID1605099Induction of hemolysis in sheep erythrocytes by measuring hemoglobin release incubated for 15 mins2020Journal of medicinal chemistry, 03-26, Volume: 63, Issue:6
Discovery of Novel Peptidomimetic Boronate ClpP Inhibitors with Noncanonical Enzyme Mechanism as Potent Virulence Blockers
AID1604186Inhibition of 20S proteasome beta 5c (unknown origin) after 1 hr by fluorescence based assay2019European journal of medicinal chemistry, Nov-15, Volume: 182Immunoproteasome-selective inhibitors: An overview of recent developments as potential drugs for hematologic malignancies and autoimmune diseases.
AID1604182Inhibition of 20S proteasome beta 1c (unknown origin) after 1 hr by fluorescence based assay2019European journal of medicinal chemistry, Nov-15, Volume: 182Immunoproteasome-selective inhibitors: An overview of recent developments as potential drugs for hematologic malignancies and autoimmune diseases.
AID1882258Inhibition of proteasome (unknown origin)2022European journal of medicinal chemistry, Feb-05, Volume: 229A review on the treatment of multiple myeloma with small molecular agents in the past five years.
AID706737Reversible inhibition of human erythrocyte derived 20S proteasome subunit beta2 after 30 mins by fluorogenic assay2012Journal of medicinal chemistry, Dec-13, Volume: 55, Issue:23
Molecular mechanisms of acquired proteasome inhibitor resistance.
AID1559513Inhibition of human 20S proteasome using Suc-LLVY-AMC as substrate measured every 5 mins for 120 mins by fluorescence based assay
AID1453444Inhibition of recombinant human C-MYC/DDK-tagged ENGase expressed in HEK293T cells at 100 uM using heat inactivated bovine ribonuclease B as substrate pretreated for 15 mins followed by substrate addition after 90 mins by SDS-PAGE analysis2017Bioorganic & medicinal chemistry letters, 07-01, Volume: 27, Issue:13
Repurposing of Proton Pump Inhibitors as first identified small molecule inhibitors of endo-β-N-acetylglucosaminidase (ENGase) for the treatment of NGLY1 deficiency, a rare genetic disease.
AID1864382Inhibition of NLRP3 inflammasome activation in LPS-primed mouse J774.A1 cells assessed as reduction in IL-1beta secretion preincubated for 1 hr followed by nigericin stimulation and measured after 1 hr by ELISA2022Journal of medicinal chemistry, 09-22, Volume: 65, Issue:18
Discovery of a Novel Oral Proteasome Inhibitor to Block NLRP3 Inflammasome Activation with Anti-inflammation Activity.
AID1396601Inhibition of chymotrypsin-like activity of human 20S proteasome using Suc-Leu-Leu-Val-Tyr-AMC as substrate incubated for 10 mins followed by substrate addition measured after 1 hr by spectrofluorimetric method2018Bioorganic & medicinal chemistry, 08-07, Volume: 26, Issue:14
Design, synthesis, in vitro and in vivo evaluation, and structure-activity relationship (SAR) discussion of novel dipeptidyl boronic acid proteasome inhibitors as orally available anti-cancer agents for the treatment of multiple myeloma and mechanism stud
AID1605098Inhibition of ClpP in methicillin-resistant Staphylococcus aureus ATCC 33591 assessed as reduction in bacteria-induced hemolysis of sheep erythrocytes by measuring hemoglobin release incubated for 15 mins2020Journal of medicinal chemistry, 03-26, Volume: 63, Issue:6
Discovery of Novel Peptidomimetic Boronate ClpP Inhibitors with Noncanonical Enzyme Mechanism as Potent Virulence Blockers
AID706736Reversible inhibition of human erythrocyte derived 20S proteasome subunit beta1 after 30 mins by fluorogenic assay2012Journal of medicinal chemistry, Dec-13, Volume: 55, Issue:23
Molecular mechanisms of acquired proteasome inhibitor resistance.
AID1396623Bioavailability in Sprague-Dawley rat at 1.2 mg/kg, ig by LC-MS/MS analysis2018Bioorganic & medicinal chemistry, 08-07, Volume: 26, Issue:14
Design, synthesis, in vitro and in vivo evaluation, and structure-activity relationship (SAR) discussion of novel dipeptidyl boronic acid proteasome inhibitors as orally available anti-cancer agents for the treatment of multiple myeloma and mechanism stud
AID1439192Drug metabolism in human plasma administered as iv bolus dose after 30 mins2017European journal of medicinal chemistry, Mar-10, Volume: 128Design, synthesis and biological evaluation of novel non-peptide boronic acid derivatives as proteasome inhibitors.
AID1296008Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening2020SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1
Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID1347103qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347098qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347124qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for RD cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347116qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SJ-GBM2 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347107qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1508630Primary qHTS for small molecule stabilizers of the endoplasmic reticulum resident proteome: Secreted ER Calcium Modulated Protein (SERCaMP) assay2021Cell reports, 04-27, Volume: 35, Issue:4
A target-agnostic screen identifies approved drugs to stabilize the endoplasmic reticulum-resident proteome.
AID1347123qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347083qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: Viability assay - alamar blue signal for LASV Primary Screen2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347100qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347102qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347101qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347094qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347095qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347128qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for OHS-50 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347099qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347109qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB1643 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347092qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347086qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lymphocytic Choriomeningitis Arenaviruses (LCMV): LCMV Primary Screen - GLuc reporter signal2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347113qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for LAN-5 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347096qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347117qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-37 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347121qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for control Hh wild type fibroblast cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347091qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347119qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347108qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347082qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: LASV Primary Screen - GLuc reporter signal2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347110qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells)2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347115qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB-EBc1 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347089qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347097qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347106qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for control Hh wild type fibroblast cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347126qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh30 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347118qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347122qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347090qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1745845Primary qHTS for Inhibitors of ATXN expression
AID1347129qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347105qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347154Primary screen GU AMC qHTS for Zika virus inhibitors2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1347114qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347125qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh18 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347111qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1346987P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1346986P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1347093qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347112qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-12 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347104qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347127qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID686947qHTS for small molecule inhibitors of Yes1 kinase: Primary Screen2013Bioorganic & medicinal chemistry letters, Aug-01, Volume: 23, Issue:15
Identification of potent Yes1 kinase inhibitors using a library screening approach.
AID1745855NCATS anti-infectives library activity on the primary C. elegans qHTS viability assay2023Disease models & mechanisms, 03-01, Volume: 16, Issue:3
In vivo quantitative high-throughput screening for drug discovery and comparative toxicology.
AID1347412qHTS assay to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: Counter screen cell viability and HiBit confirmation2020ACS chemical biology, 07-17, Volume: 15, Issue:7
High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
AID1347411qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS Mechanism Interrogation Plate v5.0 (MIPE) Libary2020ACS chemical biology, 07-17, Volume: 15, Issue:7
High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
AID1745854NCATS anti-infectives library activity on HEK293 viability as a counter-qHTS vs the C. elegans viability qHTS2023Disease models & mechanisms, 03-01, Volume: 16, Issue:3
In vivo quantitative high-throughput screening for drug discovery and comparative toxicology.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (292)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's0 (0.00)29.6817
2010's148 (50.68)24.3611
2020's144 (49.32)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 65.71

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be very strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index65.71 (24.57)
Research Supply Index5.94 (2.92)
Research Growth Index6.91 (4.65)
Search Engine Demand Index108.06 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (65.71)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials78 (26.00%)5.53%
Reviews51 (17.00%)6.00%
Case Studies18 (6.00%)4.05%
Observational4 (1.33%)0.25%
Other149 (49.67%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (152)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Open-Label Phase 1 Study to Assess the Maximum Tolerated Dose, Pharmacokinetics, and Safety of Ixazomib Administered Intravenously to Pediatric Patients Aged 0 to <18 Years With Relapsed or Refractory Acute Lymphoblastic Leukemia, With or Without Extramed [NCT03888534]Phase 10 participants (Actual)Interventional2020-10-31Withdrawn(stopped due to Business decision (no safety or efficacy concerns))
A Phase 3, Randomized, Double-Blind, Multicenter Study Comparing Oral Ixazomib (MLN9708) Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Patients With Relapsed and/or Refractory Multiple Myeloma [NCT01564537]Phase 3722 participants (Actual)Interventional2012-08-01Completed
Phase Ib/II Trial to Evaluate Safety and Efficacy of Oral Ixazomib in the Prophylaxis of Chronic Graft-versus-host Disease. [NCT03225417]Phase 1/Phase 2142 participants (Anticipated)Interventional2017-05-16Active, not recruiting
A Phase 1/2 Study of MLN9708 (Ixazomib [I]), Venetoclax (V), and Dexamethasone (D) Regimen (IVD) to Restore or Enhance Proteasome Inhibitor (PI) Sensitivity in Non-t(11;14) Relapsed/Refractory Multiple Myeloma (RRMM) [NCT03856112]Phase 1/Phase 20 participants (Actual)Interventional2019-06-21Withdrawn(stopped due to Per CTEP, Martha Khrum this study is withdrawn. Changing status to update CT.gov)
An Open-Label, Rollover Protocol for Patients Previously Enrolled in Millennium-Sponsored Ixazomib Studies [NCT02924272]Phase 231 participants (Actual)Interventional2016-12-16Active, not recruiting
A Randomized Phase II Study of DaRatumumab, Ixazomib, and Dexamethasone vs Daratumumab, Bortezomib (VElcade) and Dexamethasone Followed by Daratumumab-Ixazomib-Dexamethasone in Newly Diagnosed Multiple Myeloma (DeRIVE Study) [NCT03942224]Phase 249 participants (Actual)Interventional2019-07-03Active, not recruiting
Phase 2 Trial of Pembrolizumab, Ixazomib, and Dexamethasone for Relapsed Multiple Myeloma [NCT03506360]Phase 213 participants (Actual)Interventional2018-06-19Completed
Phase II Trial of Ixazomib and Dexamethasone Versus Ixazomib, Dexamethasone and Lenalidomide, Randomized With NFKB2 Rearrangement. (Proteasome Inhibitor NFKB2 Rearrangement Driven Trial, PINR) [NCT02765854]Phase 272 participants (Actual)Interventional2016-09-01Active, not recruiting
Phase II Randomized Trial of Continuation of Post-Transplant Maintenance With Single-Agent Lenalidomide vs. Consolidation/Maintenance With Ixazomib-Lenalidomide-Dexamethasone in Patients With Residual Myeloma [NCT02389517]Phase 242 participants (Actual)Interventional2015-03-02Active, not recruiting
A Phase 2, Multicenter, Open-label, Single-Arm Study to Evaluate the Safety and Efficacy of Daratumumab in Combination With Ixazomib and Dexamethasone as Second Line Therapy in Multiple Myeloma Patients Who Have Received Prior Treatment With a Lenalidomid [NCT03746652]Phase 250 participants (Anticipated)Interventional2018-12-31Not yet recruiting
Phase II Trial Studying the Efficacy of a Triplet Combination of MLN9708, Lenalidomide and Dexamethasone as Induction Prior to, and as Consolidation After High-dose Therapy With Peripheral Stem Cell Transplantation Followed by MLN9708 Maintenance in the I [NCT01936532]Phase 242 participants (Actual)Interventional2014-11-12Completed
A Phase I Study of the Selective Inhibitor of Nuclear Export (SINE) Selinexor in Combination With the Proteasome Inhibitor Ixazomib for the Treatment of Advanced Sarcoma [NCT03880123]Phase 10 participants (Actual)Interventional2020-11-30Withdrawn(stopped due to Study will not proceed, no participants enrolled.)
A Randomised Phase II Trial of Cyclophosphamide and Dexamethasone in Combination With Ixazomib in Relapsed or Refractory Multiple Myeloma (RRMM) Patients Who Have Relapsed After Treatment With Thalidomide, Lenalidomide and Bortezomib. [NCT02461888]Phase 2112 participants (Actual)Interventional2015-12-31Active, not recruiting
MLN9708 for the Prophylaxis of Chronic Graft-versus-host Disease in Patient Undergoing Allogeneic Transplantation [NCT02250300]Phase 1/Phase 268 participants (Actual)Interventional2014-11-19Completed
Phase I Study of the Combination of MLN9708 and Fulvestrant in Patients With Advanced Estrogen Receptor Positive Breast Cancer [NCT02384746]Phase 19 participants (Actual)Interventional2015-06-02Terminated(stopped due to Low accrual)
Myeloma XIV: A Phase III Trial to Compare Standard and Frailty-adjusted Induction Therapy With Ixazomib, Lenalidomide and Dexamethasone (IRD) and Maintenance Lenalidomide (R) to Lenalidomide Plus Ixazomib (R+I) [NCT03720041]Phase 3740 participants (Anticipated)Interventional2020-08-04Recruiting
An Open-label Phase I/II Trial of Venetoclax-Dexamethasone in Relapsed and/or Refractory t(11;14) Systemic Light-Chain Amyloidosis [NCT05451771]Phase 1/Phase 253 participants (Anticipated)Interventional2022-10-26Recruiting
Pilot Study of Ixazomib to Reduce the Number of HIV DNA Positive Lymphoid Cells [NCT02946047]Phase 1/Phase 217 participants (Actual)Interventional2017-03-20Completed
Open Label Phase II Study of Ixazomib for the Prevention of Recurrent or Late Acute and Chronic Graft-versus-Host Disease at 1-year After Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Hematologic Malignancies [NCT03082677]Phase 220 participants (Actual)Interventional2017-03-10Completed
An Open-Label, Dose-Escalation, Phase 1/2 Study of the Oral Form of Ixazomib (MLN9708), a Next-Generation Proteasome Inhibitor, Administered in Combination With a Standard Care Regimen of Melphalan and Prednisone in Patients With Newly Diagnosed Multiple [NCT01335685]Phase 1/Phase 261 participants (Actual)Interventional2011-06-27Completed
A Phase I/II Study of Ixazomib and Ibrutinib in Relapsed/Refractory Mantle Cell Lymphoma [NCT03323151]Phase 1/Phase 243 participants (Actual)Interventional2018-08-13Active, not recruiting
A Multicentre Open-label Phase II Study of Ixazomib -Daratumumab Without Dexamethasone (IDara) in Elderly Relapse Refractory Multiple Myeloma [NCT03757221]Phase 270 participants (Anticipated)Interventional2019-02-07Recruiting
A Phase 1 Study of MLN9708 in Combination With MEC (Mitoxantrone, Etoposide, and Intermediate-Dose Cytarabine) for Relapsed/ Refractory Acute Myelogenous Leukemia (AML) [NCT02070458]Phase 130 participants (Actual)Interventional2014-10-08Completed
Multicenter Phase II, Double-blind Placebo Controlled Trial of Maintenance Ixazomib After Allogeneic Hematopoietic Stem Cell Transplantation for High Risk Multiple Myeloma (BMT CTN 1302) [NCT02440464]Phase 257 participants (Actual)Interventional2015-08-31Completed
Phase I/II Study of Ixazomib and Romidepsin in Relapsed/ Refractory Peripheral T-cell Lymphoma (PTCL) [NCT03547700]Phase 1/Phase 211 participants (Actual)Interventional2018-09-26Active, not recruiting
Phase 1/2 Trial of Ixazomib in Combination With Cyclophosphamide and Dexamethasone in Patients With Previously Untreated Symptomatic Multiple Myeloma or Light Chain Amyloidosis [NCT01864018]Phase 1/Phase 287 participants (Actual)Interventional2013-08-20Active, not recruiting
Ixazomib (MLN9708) and Dexamethasone in High Risk Smoldering Multiple Myeloma: A Clinical and Correlative Pilot Study [NCT02697383]Phase 114 participants (Actual)Interventional2016-02-29Active, not recruiting
A Prospective Open-label Trial to Assess the Efficacy and Safety of Ixazomib and Dexamethasone in Patients With Refractory Autoimmune Cytopenia [NCT03965624]Phase 20 participants (Actual)Interventional2019-09-01Withdrawn(stopped due to Decision of sponsor: impossibility of contract with Takeda)
An Open-label, Single-Arm, Multicenter Study to Evaluate the Efficacy and Safety of Ixazomib in Combination With Lenalidomide and Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma Initially Treated With an Injection of Proteasome [NCT03416374]Phase 445 participants (Actual)Interventional2018-02-18Completed
Phase I/II Study Augmenting TAK-659 Action in Relapsed/Refractory AML by Addition of the Proteasome Inhibitor Ixazomib: Big Ten Cancer Research Consortium BTCRC-HEM17-092 [NCT04079738]Phase 1/Phase 28 participants (Actual)Interventional2019-09-20Terminated(stopped due to Funder requested termination due to halting internal development of TAK-659)
A Phase I/II Study of the Addition of Ixazomib to ONC201 and Dexamethasone in Relapsed and/or Refractory Multiple Myeloma [NCT03492138]Phase 1/Phase 25 participants (Actual)Interventional2018-03-26Terminated(stopped due to Low enrollment)
Ixazomib in Combination With Thalidomide - Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma [NCT02410694]Phase 290 participants (Actual)Interventional2015-04-30Completed
Toward a Risk-adapted Strategy to Cure Myeloma : An Intensive Program With Lenalidomide, Ixazomib, and Dexamethasone Plus Daratumumab as Extended Induction and Consolidation Followed by Lenalidomide Maintenance in Newly Diagnosed Standard Risk Multiple My [NCT03669445]Phase 245 participants (Anticipated)Interventional2018-12-31Recruiting
A Phase 2 Open-Label Pilot Study of the Safety and Tolerability of Ixazomib Administered Orally to Patients With Scleroderma-Related Interstitial Lung Disease [NCT04837131]Phase 212 participants (Anticipated)Interventional2021-04-28Recruiting
Phase II Study of the Combination of Daratumumab, Ixazomib, Pomalidomide, and Dexamethasone as Salvage Therapy in Relapsed/Refractory Multiple Myeloma A University of California Hematologic Malignancies Consortium Protocol (UCHMC1809) [NCT03590652]Phase 246 participants (Anticipated)Interventional2018-10-17Active, not recruiting
A Multicenter, Open-label, Prospective Study of Ixazomib, Lenalidomide, and Ixazomib in Combination With Lenalidomide for Maintenance Therapy in Patients With Newly Diagnosed Multiple Myeloma [NCT04217967]Phase 4180 participants (Anticipated)Interventional2020-01-03Recruiting
A Phase IB/II Trial of Lenalidomide (Revlimid®), Ixazomib and Rituximab (RIXAR) as Front-line Therapy for High Risk Indolent B Cell Lymphoma [NCT02898259]Phase 1/Phase 219 participants (Actual)Interventional2017-02-20Terminated(stopped due to Funding was eliminated.)
A Phase I-II Trial of DA-EPOCH-R Plus Ixazomib as Frontline Therapy for Patients With MYC-aberrant Lymphoid Malignancies: The DACIPHOR Regimen [NCT02481310]Phase 1/Phase 238 participants (Actual)Interventional2015-10-28Active, not recruiting
An Open-Label, Single-Arm Phase II Study of Ixazomib, Thalidomide and Dexamethasone in Newly Diagnosed and Treatment-Naive Multiple Myeloma Patients Non-Eligible for Autologous Stem-Cell Transplantation [NCT03608501]Phase 20 participants (Actual)Interventional2019-09-30Withdrawn(stopped due to Business decision (no safety or efficacy concerns))
A Phase 2, Open-Label, Multicenter Study of Ixazomib Plus Lenalidomide and Dexamethasone in Adult Japanese Patients With Relapsed and/or Refractory Multiple Myeloma [NCT02917941]Phase 234 participants (Actual)Interventional2016-11-01Completed
A Phase I/II Study of MLN9708 as Post-Transplant Maintenance for Patients With Mantle Cell Lymphoma Undergoing Autologous Stem Cell Transplant in First Remission [NCT02632396]Phase 1/Phase 212 participants (Actual)Interventional2016-03-01Active, not recruiting
Optimizing Prolonged Treatment In Myeloma Using MRD Assessment (OPTIMUM) [NCT03941860]Phase 3510 participants (Anticipated)Interventional2022-02-16Active, not recruiting
A Prospective, Multicenter, Observational Study in Relapsed and/or Refractory Multiple Myeloma Patients Treated With Ixazomib Plus Lenalidomide and Dexamethasone [NCT03433001]295 participants (Actual)Observational2018-04-02Completed
"NINLARO Capsules Drug Use-Results Survey (All-Case Surveillance) Relapsed/Refractory Multiple Myeloma" [NCT03169361]774 participants (Actual)Observational2017-05-24Completed
A Phase 3, Randomized, Double-Blind, Multicenter Study Comparing Oral MLN9708 Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Patients With Newly Diagnosed Multiple Myeloma [NCT01850524]Phase 3705 participants (Actual)Interventional2013-04-29Completed
Phase I Study of MLN 9708 in Addition to Chemotherapy for the Treatment of Acute Lymphoblastic Leukemia in Older Adults [NCT02228772]Phase 119 participants (Actual)Interventional2014-12-31Completed
Phase 1 / 2 Trial of Idasanutlin in Combination With Ixazomib and Dexamethasone in Patients With 17p Deleted, Relapsed Multiple Myeloma [NCT02633059]Phase 1/Phase 233 participants (Actual)Interventional2015-12-30Active, not recruiting
A Phase 3, Randomized, Placebo-Controlled, Double-Blind Study of Oral Ixazomib Maintenance Therapy After Initial Therapy in Patients With Newly Diagnosed Multiple Myeloma Not Treated With Stem Cell Transplantation [NCT02312258]Phase 3706 participants (Actual)Interventional2015-04-09Completed
A Phase I Study of Ixazomib and Erlotinib in Advanced Solid Tumor Patients [NCT02942095]Phase 19 participants (Actual)Interventional2017-03-06Completed
Phase 2 Trial of Pomalidomide, Ixazomib and Dexamethasone in Patients With Multiple Myeloma With Extramedullary Disease or Plasma Cell Leukemia [NCT02547662]Phase 217 participants (Actual)Interventional2015-12-24Completed
A Phase 1 Study of MLN9708 in Japanese Patients With Relapsed and/or Refractory Multiple Myeloma [NCT04272775]Phase 114 participants (Actual)Interventional2012-06-05Terminated(stopped due to Business Decision; No Safety Or Efficacy Concerns)
Myeloma-Developing Regimens Using Genomics (MyDRUG) (Genomics Guided Multi-arm Trial of Targeted Agents Alone or in Combination With a Backbone Regimen) [NCT03732703]Phase 1/Phase 2228 participants (Anticipated)Interventional2019-04-01Recruiting
A Prospective Phase 2 Study to Assess the Minimal Residual Disease After Ixazomib Plus Lenalidomide Plus Dexamethasone (IRd) Treatment for Newly Diagnosed Transplant Eligible Myeloma Patients [NCT03376672]Phase 2120 participants (Actual)Interventional2018-05-31Active, not recruiting
A Phase 1 Pharmacokinetic and Tolerability Study of Oral MLN9708 Plus Lenalidomide and Dexamethasone in Adult Asian Patients With Relapsed and/or Refractory Multiple Myeloma [NCT01645930]Phase 143 participants (Actual)Interventional2012-12-17Completed
Phase II Study of Targeting CD28 in Multiple Myeloma With Abatacept (CTLA4-Ig) to Overcome Resistance to Chemotherapy [NCT03457142]Phase 215 participants (Actual)Interventional2018-09-11Active, not recruiting
An Open-Label, Single-Arm, Multicenter Study to Evaluate the Effectiveness and Safety of Ixazomib (NINLARO®) in Combination With Lenalidomide and Dexamethasone (IRD) in Patients With Multiple Myeloma Previously Receiving a Bortezomib-Based Induction Regim [NCT03173092]Phase 4141 participants (Actual)Interventional2017-09-20Active, not recruiting
A Multi-center, Open-label, Single-arm Clinical Study of Ixazomib/Pomalidomide/Dexamethasone (IxaPD) in the Treatment of Patients With Relapsed Multiple Myeloma [NCT04989140]Phase 460 participants (Anticipated)Interventional2021-07-26Recruiting
A Phase III Study to Determine the Role of Ixazomib as an Augmented Conditioning Therapy in Salvage Autologous Stem Cell Transplant (ASCT) and as a Post-ASCT Consolidation and Maintenance Strategy in Patients With Relapsed Multiple Myeloma [NCT03562169]Phase 3406 participants (Anticipated)Interventional2017-03-20Recruiting
A Phase I Two-Dimensional Dose-Finding Study of Ixazomib in Combination With Gemcitabine and Doxorubicin, Followed by a Phase II Extension to Assess the Efficacy of This Combination in Metastatic, Surgically Unresectable Urothelial Cancer [NCT02420847]Phase 1/Phase 257 participants (Anticipated)Interventional2015-07-03Active, not recruiting
A Phase 2, Open Label, Randomized Trial Evaluating Ixazomib Compared to Ixazomib-Lenalidomide Combination Maintenance Therapy for Frontline Multiple Myeloma Patients [NCT03733691]Phase 219 participants (Actual)Interventional2019-03-01Terminated(stopped due to Insufficient enrollment)
Phase II Study Of Ixazomib As Maintenance Therapy For Patients With Acute Myeloid Leukemia (AML) And High Risk Myelodysplastic Syndrome (MDS) In Remission [NCT02302846]Phase 25 participants (Actual)Interventional2015-03-20Terminated(stopped due to Slow Accrual)
Alternating the Administration of Ixazomib and Lenalidomide as Maintenance Therapy After Autologous Transplant for Treating Multiple Myeloma [NCT02619682]Phase 230 participants (Actual)Interventional2015-12-30Active, not recruiting
Bone Healing During Ninlaro Exposure. An Open Label Phase 2 Single Centre Clinical Trial [NCT04028115]Phase 230 participants (Anticipated)Interventional2019-10-24Active, not recruiting
A Phase II Trial of a Novel Proteasome/IMiD Combination, Ixazomib, Pomalidomide, and Dexamethasone in Relapsed Multiple Myeloma Patients [NCT02578121]Phase 20 participants (Actual)Interventional2015-12-31Withdrawn(stopped due to Investigator decided to close study without enrollment)
Multicenter Open Label Phase 2 Single Arm Study of Ixazomib, Pomalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma Characterized With Genomic Abnormalities of Adverse Adverse Prognostic [NCT03683277]Phase 226 participants (Actual)Interventional2019-11-03Terminated(stopped due to Recruitment issue, 26 patients enrolled instead of 70 initially planned)
A Phase 2 Study of Subcutaneous Daratumumab in Combination With Dose-Attenuated Bortezomib, Lenalidomide, and Dexamethasone in Elderly Newly Diagnosed Multiple Myeloma Patients [NCT04052880]Phase 238 participants (Anticipated)Interventional2019-10-24Recruiting
Phase I/II Trial of MLN9708 Plus Pomalidomide and Dexamethasone for Relapsed or Relapsed Refractory Multiple Myeloma [NCT02119468]Phase 1/Phase 232 participants (Actual)Interventional2014-06-30Active, not recruiting
A Phase 2, Randomized, Open-Label Study Comparing Oral Ixazomib/Dexamethasone and Oral Pomalidomide/Dexamethasone in Relapsed and/or Refractory Multiple Myeloma [NCT03170882]Phase 2122 participants (Actual)Interventional2017-08-01Completed
"A Multi-center Open-label Phase 2 Study of Ixazomib, Iberdomide and Dexamethasone in Elderly Patients With Multiple Myeloma at First Relapse." [NCT04998786]Phase 280 participants (Anticipated)Interventional2021-12-14Active, not recruiting
China Continuation: A Single-Arm, Open-Label Study of Oral Ixazomib Maintenance Therapy After Initial Therapy in Patients With Newly Diagnosed Multiple Myeloma Not Treated With Stem Cell Transplantation [NCT03748953]Phase 331 participants (Actual)Interventional2019-01-24Completed
Phase I Clinical Trial of Venetoclax (ABT-199) in Combination With Ixazomib and Dexamethasone for Patients With Relapsed Multiple Myeloma [NCT03399539]Phase 17 participants (Actual)Interventional2018-05-02Active, not recruiting
An Open-Label, Dose-Escalation, Phase 1 Study of IXAZOMIB (MLN9708), A Second-Generation Proteasome Inhibitor, in Adult Patients With Lymphoma [NCT00893464]Phase 131 participants (Actual)Interventional2009-08-31Completed
An Investigator-Initiated Phase I Study of Selinexor (KPT-330), Ixazomib, and Low Dose Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma [NCT02831686]Phase 118 participants (Actual)Interventional2016-07-31Completed
An Open-Label, Dose Escalation, Phase 1 Study of IXAZOMIB (MLN9708), a Second-Generation Proteasome Inhibitor, in Adult Patients With Advanced Nonhematologic Malignancies [NCT00830869]Phase 1116 participants (Actual)Interventional2009-03-02Completed
A Single-arm, Multisite, Prospective Study of Ixazomib-pomalidomide-dexamethasone as Second or Third-line Combination Treatment for Patients With Relapsed and Refractory Multiple Myeloma (RRMM) Previously Treated With Daratumumab, Lenalidomide and Bortezo [NCT04790474]Phase 260 participants (Anticipated)Interventional2021-03-25Recruiting
MLN9708 (Ixazomib) and MLN4924 (Pevonedistat) in Relapsed/Refractory Multiple Myeloma Patients: A Phase 1b Trial [NCT03770260]Phase 18 participants (Actual)Interventional2020-02-10Completed
An Open-Label, Non-Comparative, Two-Cohort, Multicenter Study to Evaluate the Effectiveness and Safety of Ixazomib (NINLARO®) in Combination With Pomalidomide and Dexamethasone (IPd, Cohort A) or With Lenalidomide and Dexamethasone (IRd, Cohort B) in Pati [NCT05183139]Phase 40 participants (Actual)Interventional2022-06-30Withdrawn(stopped due to Business decision (no enrollment))
Standard Maintenance [POMP/D (Methotrexate, 6 - Mercaptopurine, Vincristine, Prednisone/Dexamethasone)] Plus Ixazomib Maintenance Therapy in Adults With Acute Lymphoblastic Leukemia, Lymphoblastic Lymphoma or Mixed Phenotype Acute Leukemia in Complete Rem [NCT02578511]Phase 10 participants (Actual)Interventional2017-06-29Withdrawn(stopped due to No enrollment, another competing study and difficult to find the right person to enroll on this study.)
A Phase II Study of IRD (Ixazomib, Lenalidomide, & Dexamethasone) for Consolidation Therapy Post Autologous Stem Cell Transplantation Followed by Maintenance Ixazomib or Lenalidomide for Multiple Myeloma [NCT02253316]Phase 2236 participants (Actual)Interventional2015-01-20Active, not recruiting
A Phase 1/1a Study of Venetoclax, MLN9708 (Ixazomib Citrate) and Dexamethasone for Relapsed/Refractory Light Chain Amyloidosis [NCT04847453]Phase 124 participants (Anticipated)Interventional2022-08-03Recruiting
Phase II Trial of Combination of Ixazomib and Lenalidomide and Dexamethasone in Smoldering Multiple Myeloma [NCT02916771]Phase 255 participants (Actual)Interventional2016-10-31Active, not recruiting
An Open-Label, Dose-Escalation, Phase 1 Study of the Oral Form of Ixazomib (MLN9708), a Second-Generation Proteasome Inhibitor, in Adult Patients With Relapsed and/or Refractory Multiple Myeloma [NCT00932698]Phase 160 participants (Actual)Interventional2009-10-12Completed
Phase 2 Trial of Induction With Ixazomib, Pomalidomide, Dexamethasone Prior to Salvage Autologous Stem Cell Transplant Followed by Consolidation With Ixazomib, Pomalidomide, and Dexamethasone and Ixazomib Maintenance in Multiple Myeloma [NCT03202628]Phase 28 participants (Actual)Interventional2017-07-24Completed
A Phase 3, Randomized, Controlled, Open-label, Multicenter, Safety and Efficacy Study of Dexamethasone Plus MLN9708 or Physicians Choice of Treatment Administered to Patients With Relapsed or Refractory Systemic Light Chain (AL) Amyloidosis [NCT01659658]Phase 3177 participants (Actual)Interventional2012-12-12Terminated(stopped due to Sponsor's decision)
An Open-Label, Dose-Escalation, Phase 1 Study of the Oral Formulation of MLN9708 Administered Weekly in Adult Patients With Relapsed or Refractory Light-Chain (AL) Amyloidosis Who Require Further Treatment [NCT01318902]Phase 127 participants (Actual)Interventional2011-04-27Completed
A Window Study of Ixazomib in Untreated Indolent B-NHL [NCT02339922]Phase 233 participants (Actual)Interventional2016-05-19Active, not recruiting
Quality of Life, Symptoms and Treatment Satisfaction in Adult Patients With Relapsed and/or Refractory Multiple Myeloma, Receiving Ixazomib (Ninlaro®) in Combination With Lenalidomide and Dexamethasone in a Real World Setting: Pilot Study [NCT03903406]40 participants (Anticipated)Observational2019-05-31Not yet recruiting
An Open-Label, Dose-Escalation, Phase 1/2 Study of the Oral Form of Ixazomib (MLN9708), a Second-Generation Proteasome Inhibitor, Administered in Combination With Lenalidomide and Low-Dose Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Re [NCT01217957]Phase 1/Phase 265 participants (Actual)Interventional2010-11-22Completed
An Open-Label, Dose-Escalation, Phase 1 Study Evaluating the Safety and Tolerability of Weekly Dosing of the Oral Form of MLN9708, a Second-Generation Proteasome Inhibitor, in Adult Patients With Relapsed and Refractory Multiple Myeloma [NCT00963820]Phase 160 participants (Actual)Interventional2009-10-31Completed
Evaluation of Ixazomib, Lenalidomide, Dexamethasone Induction and Extended Consolidation Followed by Lenalidomide Maintenance in Newly Diagnosed Multiple Myeloma Patients ≤65 Years Eligible for High Dose Therapy [NCT02897830]Phase 246 participants (Actual)Interventional2016-08-05Terminated(stopped due to negatives results)
Phase I/II Study of Ixazomib in Combination With Pomalidomide, Clarithromycin and Dexamethasone (PiC-D) in Patients With Double Refractory Multiple Myeloma [NCT02542657]Phase 1/Phase 230 participants (Actual)Interventional2015-10-31Active, not recruiting
Ixazomib (MLN9708) in Combination With Carboplatin in Pretreated Women With Advanced Triple Negative Breast Cancer [NCT02993094]Phase 1/Phase 231 participants (Actual)Interventional2016-11-21Terminated(stopped due to Due to slow recruitment, the study had to be terminated prematurely.)
A Phase II Study of Nivolumab in Combination With Ixazomib, Cyclophosphamide, and Dexamethasone in Relapsed and Refractory Multiple Myeloma [NCT04119336]Phase 22 participants (Actual)Interventional2020-02-14Terminated(stopped due to Study closure initiated by industry funding sponsor for commercial reasons.)
A Phase 2 Study of Ixazomib and Rituximab in Bruton Tyrosine Kinase Inhibitor Resistant Mantle Cell Lymphoma [NCT04047797]Phase 224 participants (Actual)Interventional2019-08-28Active, not recruiting
Phase II Trial of Ixazomib Combined With Gemcitabine and Doxorubicin in Patients With Renal Medullary Carcinoma [NCT03587662]Phase 230 participants (Anticipated)Interventional2018-08-17Recruiting
Multicenter Phase II Study of Ixazomib Maintenance in Patients With Newly Diagnosed Mantle Cell Lymphoma [NCT03616782]Phase 298 participants (Anticipated)Interventional2018-12-24Recruiting
Phase 2 Trial of Ixazomib Combinations in Patients With Relapsed Multiple Myeloma [NCT01415882]Phase 2108 participants (Actual)Interventional2012-01-31Active, not recruiting
Phase II Study of Ibrutinib in Combination With Ixazomib in Patients With Waldenström Macroglobulinemia [NCT03506373]Phase 223 participants (Actual)Interventional2018-07-05Active, not recruiting
Pomalidomide, Ixazomib, and Dexamethasone (PId) With or Without Intensification by Cyclophosphamide (PICd): A Phase II Study in Relapsed or Refractory Multiple Myeloma [NCT03731832]Phase 282 participants (Anticipated)Interventional2018-09-20Active, not recruiting
A Phase 2 Clinical Trial to Evaluate the Efficacy of Zanubrutinib Plus Ixazomib and Dexamethasone in Newly Diagnosed Symptomatic Waldenström Macroglobulinemia [NCT04463953]Phase 255 participants (Anticipated)Interventional2020-05-20Recruiting
A Phase 1b/2 Study of Selinexor (KPT-330) in Combination With Backbone Treatments for Relapsed/Refractory Multiple Myeloma and Newly Diagnosed Multiple Myeloma [NCT02343042]Phase 1/Phase 2518 participants (Actual)Interventional2015-10-31Active, not recruiting
A Phase I/II Study of MLN9708 (Ixazomib) in Combination With Panobinostat and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma [NCT02057640]Phase 1/Phase 216 participants (Actual)Interventional2014-05-22Completed
Phase 1 Study of Tasquinimod Alone and in Combination With Standard Therapy for Relapsed or Refractory Myeloma [NCT04405167]Phase 134 participants (Anticipated)Interventional2020-07-10Recruiting
MLN9708 and Dexamethasone in High Risk Smoldering Multiple Myeloma: A Clinical and Correlative Pilot Study [NCT01660997]Phase 20 participants (Actual)Interventional2012-07-30Withdrawn
An Open-Label, Dose-Escalation, Phase 1/2 Study of the Oral Formulation of IXAZOMIB (MLN9708), Administered Twice-weekly in Combination With Lenalidomide and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Requiring Systemic Treatment [NCT01383928]Phase 1/Phase 264 participants (Actual)Interventional2011-10-31Completed
Phase II Study of the Combination of MLN 9708 With Lenalidomide as Maintenance Therapy Post Autologous Stem Cell Transplant in Patients With Multiple Myeloma [NCT01718743]Phase 283 participants (Actual)Interventional2012-12-03Completed
Phase II Prospective Evaluation of Bone Remodeling During Ixazomib Treatment Relapsed/Refractory Multiple Myeloma Patients [NCT02499081]Phase 220 participants (Actual)Interventional2015-09-30Completed
Phase I/II Study of Twice Weekly Ixazomib Plus Pomalidomide and Dexamethasone in Relapsed/or Refractory Multiple Myeloma [NCT04094961]Phase 1/Phase 261 participants (Anticipated)Interventional2019-09-18Recruiting
Phase I Study Of Vincristine, Doxorubicin, And Dexamethasone (VXD) Plus Ixazomib In Adults With Relapsed Or Refractory Acute Lymphoblastic Leukemia/Lymphoma, Lymphoblastic Lymphoma Or Mixed Phenotype Acute Leukemia [NCT01887587]Phase 15 participants (Actual)Interventional2013-06-30Terminated(stopped due to SAE- risk of overall protocol treatment outweighs benefits)
Phase II Trial of Ixazomib, Dexamethasone and Rituximab in Patients With Untreated Waldenstrom's Macroglobulinemia [NCT02400437]Phase 226 participants (Actual)Interventional2015-04-30Completed
Phase I Dose Escalation Study of Millennium 9708 in Combination With Induction and Consolidation Chemotherapy in Adults >= 60 Years With Acute Myeloid Leukemia [NCT02582359]Phase 139 participants (Actual)Interventional2016-01-31Completed
BrUOG 299: Ixazomib, Oral Metronomic Cyclophosphamide and Dexamethasone for First-Line Treatment of Multiple Myeloma: A Phase II Brown University Oncology Group Study. [NCT02412228]Phase 212 participants (Actual)Interventional2015-08-31Active, not recruiting
A TACL Phase 1/2 Study of PO Ixazomib in Combination With Chemotherapy for Childhood Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma IND# 140730 [NCT03817320]Phase 1/Phase 231 participants (Anticipated)Interventional2019-02-12Recruiting
[NCT02406144]Phase 3316 participants (Actual)Interventional2014-11-30Completed
Id and Rd Maintenance Regimens After Induction of Remission in Multiple Myeloma: a Prospective, Randomized, Controlled, Multicenter Clinical Study [NCT05477797]420 participants (Anticipated)Interventional2023-02-15Not yet recruiting
A Phase II Study of Lenalidomide, Ixazomib, Dexamethasone, and Daratumumab in Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma [NCT04009109]Phase 2188 participants (Anticipated)Interventional2020-10-21Recruiting
A Phase I/II Study of Pomalidomide, Dexamethasone and Ixazomib vs. Pomalidomide and Dexamethasone for Patients With Multiple Myeloma Relapsing on Lenalidomide as Part of First Line Therapy [NCT02004275]Phase 1/Phase 2118 participants (Actual)Interventional2014-02-28Active, not recruiting
A Phase I Dose Escalation Study of Nelfinavir Plus MLN9708 in Patients With Advanced Solid Tumors or Lymphoma [NCT03422874]Phase 10 participants (Actual)Interventional2016-08-31Withdrawn(stopped due to Sponsor withdrew support)
A Phase 1 Pharmacokinetic Study of Oral IXAZOMIB (MLN9708) in Patients With Advanced Solid Tumors or Hematologic Malignancies With Varying Degrees of Liver Dysfunction [NCT01912222]Phase 148 participants (Actual)Interventional2013-08-31Completed
A MULTIARM, OPEN LABEL, RANDOMIZED PHASE II STUDY OF MLN9708 PLUS ORAL DEXAMETHASONE or PLUS ORAL CYCLOPHOSPHAMIDE AND DEXAMETHASONE or PLUS ORAL THALIDOMIDE AND DEXAMETHASONE FOLLOWED BY MAINTENANCE WITH MLN9708 IN NEWLY DIAGNOSED ELDERLY MULTIPLE MYELOM [NCT02586038]Phase 2175 participants (Anticipated)Interventional2015-10-31Active, not recruiting
Exploratory Study of Ixazomib in Combination With Reduced Dose Lenalidomide Versus Ixazomib Alone for Maintenance Treatment of High Risk Multiple Myeloma [NCT05722405]Phase 4100 participants (Anticipated)Interventional2022-07-01Recruiting
Ixazomib for Treatment of Chronic Graft vs. Host Disease [NCT02513498]Phase 250 participants (Actual)Interventional2015-12-08Completed
Phase 0 Analysis of Ixazomib (MLN9708) in Patients With Glioblastoma [NCT02630030]Early Phase 13 participants (Actual)Interventional2016-03-24Completed
A Phase I Study of MLN9708 and Vorinostat to Target Autophagy in Patients With Advanced p53 Mutant Malignancies [NCT02042989]Phase 168 participants (Actual)Interventional2014-06-27Completed
Allogeneic Stem Cell Transplantation vs. Conventional Therapy as Salvage Therapy for Relapsed / Progressive Patients With Multiple Myeloma After First-line Therapy [NCT05675319]Phase 3482 participants (Anticipated)Interventional2023-03-03Recruiting
An Open-Label, Phase 2 Study to Evaluate the Oral Combination of Ixazomib (MLN9708) With Cyclophosphamide and Dexamethasone in Patients With Newly Diagnosed or Relapsed and/or Refractory Multiple Myeloma Requiring Systemic Treatment [NCT02046070]Phase 2148 participants (Actual)Interventional2014-03-05Completed
Phase I/II Trial of Mezigdomide Plus Ixazomib and Dexamethasone for Relapsed and Refractory Multiple Myeloma [NCT06050512]Phase 1/Phase 234 participants (Anticipated)Interventional2023-10-02Recruiting
A Phase 2 Study of Daratumumab, Bortezomib, and Dexamethasone (DVd), Followed by Daratumumab, Ixazomib, and Dexamethasone (DId) for Relapsed and/or Refractory Myeloma [NCT03763162]Phase 260 participants (Anticipated)Interventional2019-01-17Recruiting
Phase 2 Trial of Ixazomib, Lenalidomide, Dexamethasone, and Daratumumab in Patients With Newly Diagnosed Multiple Myeloma [NCT03012880]Phase 280 participants (Actual)Interventional2017-04-12Active, not recruiting
Safety of Ixazomib Targeting Plasma Cells in Multiple Sclerosis: A Phase 1b Randomised, Double-blind, Placebo-controlled Trial. [NCT03783416]Phase 172 participants (Anticipated)Interventional2020-08-20Recruiting
Ixazomib for Desensitization in Kidney Transplantation [NCT03213158]Phase 210 participants (Actual)Interventional2017-09-15Completed
A Phase 2, Open-Label Study of Ixazomib+Daratumumab+Dexamethasone (IDd) in Relapsed and/or Refractory Multiple Myeloma (RRMM) [NCT03439293]Phase 261 participants (Actual)Interventional2018-03-13Completed
A Phase 3, Multicenter, Randomized, Open-label Study to Compare the Efficacy and Safety of bb2121 Versus Standard Regimens in Subjects With Relapsed and Refractory Multiple Myeloma (RRMM) (KarMMa-3) [NCT03651128]Phase 3381 participants (Actual)Interventional2019-04-16Active, not recruiting
Open-label, Single-center Phase II Study of MLN9708 (Ixazomib) in Patients With Relapsed/Refractory Cutaneous and Peripheral T-cell Lymphomas [NCT02158975]Phase 213 participants (Actual)Interventional2014-09-30Completed
A Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Safety, Tolerability and Pharmacokinetic Study of Multiple Rising Doses of MLN9708 for the Treatment of Subjects With ISN / RPS Class III or IV Lupus Nephritis [NCT02176486]Phase 112 participants (Actual)Interventional2014-06-09Terminated(stopped due to Insufficient enrollment, no safety or efficacy concerns)
Phase 1/1b Pharmacokinetics Study of Oral MLN9708 in Patients With Relapsed/Refractory Multiple Myeloma and Advanced Solid Tumors With Normal Renal Function or Severe Renal Impairment [NCT01830816]Phase 141 participants (Actual)Interventional2013-09-16Completed
Phase 1/2 Study Of Ixazomib In Combination With Cyclophosphamide And Dexamethasone In Patients With Newly Diagnosed Immunoglobulin Light Chain AL Amyloidosis [NCT03236792]Phase 1/Phase 228 participants (Actual)Interventional2017-06-12Completed
A Phase 2 Study of Single-Agent MLN9708 for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia With Mutated Nucleophosmin-1 [NCT02030405]Phase 24 participants (Actual)Interventional2014-03-31Terminated(stopped due to Regulatory)
A Phase 3, Randomized, Placebo-Controlled, Double-Blind Study of Oral Ixazomib Citrate (MLN9708) Maintenance Therapy in Patients With Multiple Myeloma Following Autologous Stem Cell Transplant [NCT02181413]Phase 3656 participants (Actual)Interventional2014-07-01Active, not recruiting
A Phase 1 Study of Oral IXAZOMIB (MLN9708) to Assess Relative Bioavailability, Food Effect, Drug-Drug Interaction With Ketoconazole, Clarithromycin or Rifampin; and Safety and Tolerability in Patients With Advanced Nonhematologic Malignancies or Lymphoma [NCT01454076]Phase 1112 participants (Actual)Interventional2011-11-10Completed
A Phase 2 Trial of Ixazomib for Kaposi Sarcoma [NCT04305691]Phase 241 participants (Anticipated)Interventional2023-11-07Recruiting
Ixazomib, Lenalidomide, and Dexamethasone for Patients With POEMS Syndrome [NCT02921893]Early Phase 121 participants (Actual)Interventional2016-10-31Active, not recruiting
A Phase II Trial of Nonmyeloablative Haploidentical Peripheral Blood Stem Cell Transplantation Followed By Maintenance Therapy With the Novel Oral Proteasome Inhibitor, MLN9708, in Patients With High-risk Hematologic Malignancies [NCT02169791]Phase 229 participants (Actual)Interventional2014-07-15Completed
Ixazomib Maintenance Following Initial Therapy in Patients With Immunoglobulin Light Chain (AL) Amyloidosis [NCT03618537]Phase 217 participants (Actual)Interventional2018-08-02Active, not recruiting
A Safety Study of Daratumumab, Ixazomib, and Dexamethasone in AL Amyloidosis [NCT03283917]Phase 121 participants (Actual)Interventional2018-02-07Active, not recruiting
A Feasibility Study of Myeloablative BEAM Allogeneic Transplantation Followed by Oral Ixazomib Maintenance Therapy in Patients With Relapsed High-Risk Multiple Myeloma [NCT02504359]Phase 111 participants (Actual)Interventional2015-07-20Completed
Solitary Plasmacytoma of Bone: Randomized Phase III Trial to Evaluate Treatment With Adjuvant Systemic Treatment and Zoledronic Acid Versus Zoledronic Acid After Definite Radiation Therapy [NCT02516423]Phase 311 participants (Actual)Interventional2015-12-31Active, not recruiting
A Phase 1 Study of [ 14 C]-Ixazomib to Assess Mass Balance, Pharmacokinetics, and Metabolism in Patients With Advanced Solid Tumors or Lymphoma [NCT01953783]Phase 17 participants (Actual)Interventional2014-03-19Completed
Phase I/II Study of Bendamustine and IXAZOMIB (MLN9708) Plus Dexamethasone in Relapsed/Refractory Multiple Myeloma [NCT02477215]Phase 1/Phase 238 participants (Actual)Interventional2015-10-09Completed
Phase I/II Study of Ixazomib With Pegylated IFN-alpha 2b (pIFN) in Metastatic Renal Cell Carcinoma (mRCC) [NCT02447887]Phase 1/Phase 23 participants (Actual)Interventional2015-08-14Terminated(stopped due to IRB study closure facilitated by Investigator)
An Open-label, Multicenter, Phase 2 Study of Oral IXAZOMIB (MLN9708) in Adult Patients With Relapsed and/or Refractory Follicular Lymphoma [NCT01939899]Phase 229 participants (Actual)Interventional2013-10-31Completed
Open-Label Study to Determine the Feasibility of MLN9708 as Maintenance After Allogeneic Stem Cell Transplant for Multiple Myeloma, Followed by an Expansion Phase at the Maximum-Tolerated Dose (MTD) - A Phase II Study [NCT02168101]Phase 29 participants (Actual)Interventional2014-09-30Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00830869 (13) [back to overview]Part 1: AUC (0-72): Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours Post-dose for Ixazomib
NCT00830869 (13) [back to overview]Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs)
NCT00830869 (13) [back to overview]Part 2: Ixazomib Concentration in Postdose Clinical Tumor Samples in Ixazomib 1.76 mg/m^2-TPEC
NCT00830869 (13) [back to overview]Part 1: Terminal Phase Elimination Half-life (T1/2) for Ixazomib
NCT00830869 (13) [back to overview]Part 1: Rac: Accumulation Ratio for Ixazomib
NCT00830869 (13) [back to overview]Part 1: Number of Participants With Dose Limiting Toxicity (DLT)
NCT00830869 (13) [back to overview]Number of Participants With Clinically Significant Change From Baseline in Vital Signs
NCT00830869 (13) [back to overview]Part 1: TEmax: Time to Maximum Observed Effect (Emax) for Ixazomib
NCT00830869 (13) [back to overview]Part 1: E Max: Maximum Observed Effect for Ixazomib
NCT00830869 (13) [back to overview]Part 1: C0: Initial Plasma Concentration After Bolus Intravenous Administration
NCT00830869 (13) [back to overview]Part 1: AUC (0-72): Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours Post-dose for Ixazomib
NCT00830869 (13) [back to overview]Number of Participants With Clinically Significant TEAEs Related to Laboratory Abnormalities
NCT00830869 (13) [back to overview]Number of Participants With Best Overall Response
NCT00893464 (15) [back to overview]Number of Participants With Clinically Significant Change From Baseline in Vital Signs
NCT00893464 (15) [back to overview]Maximum Tolerated Dose (MTD)
NCT00893464 (15) [back to overview]Terminal Phase Elimination Half-life (T1/2) for Ixazomib
NCT00893464 (15) [back to overview]CLr: Renal Clearance
NCT00893464 (15) [back to overview]AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for Ixazomib
NCT00893464 (15) [back to overview]C0: Initial Plasma Concentration After Bolus Intravenous Administration
NCT00893464 (15) [back to overview]TEmax: Time to Maximum Observed Effect (Emax) for Ixazomib
NCT00893464 (15) [back to overview]Ae (0-4): Amount of Drug Excreted in Urine From 0 to 4 Hours Postdose
NCT00893464 (15) [back to overview]Overall Best Response
NCT00893464 (15) [back to overview]Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
NCT00893464 (15) [back to overview]Rac: Accumulation Ratio for Ixazomib
NCT00893464 (15) [back to overview]Number of Participants Reporting at Least 1 TEAE Related to Laboratory Assessments
NCT00893464 (15) [back to overview]Fe (0-4): Fraction of Dose Excreted Unchanged in Urine From 0 to 4 Hours Postdose
NCT00893464 (15) [back to overview]Emax: Maximum Observed Effect for Ixazomib
NCT00893464 (15) [back to overview]Recommended Phase 2 Dose (RP2D)
NCT00932698 (14) [back to overview]AUC(0-last): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ixazomib
NCT00932698 (14) [back to overview]Cmax: Maximum Observed Plasma Concentration for Ixazomib
NCT00932698 (14) [back to overview]Recommended Phase 2 Dose (RP2D) of Ixazomib
NCT00932698 (14) [back to overview]Number of Participants With Clinically Significant Changes in Vital Signs Reported as TEAEs
NCT00932698 (14) [back to overview]Number of Participants With Clinically Significant Abnormalities Reported as TEAEs
NCT00932698 (14) [back to overview]Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib
NCT00932698 (14) [back to overview]Number of Participants With One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
NCT00932698 (14) [back to overview]Overall Response Rate (ORR)
NCT00932698 (14) [back to overview]Number of Participants With a TEAE of Peripheral Neuropathy
NCT00932698 (14) [back to overview]T1/2: Terminal Disposition Phase Elimination Half-life for Ixazomib
NCT00932698 (14) [back to overview]λz: Terminal Disposition Phase Rate Constant for Ixazomib
NCT00932698 (14) [back to overview]Maximum Tolerated Dose (MTD) of Ixazomib
NCT00932698 (14) [back to overview]AUC(0-72): Area Under the Plasma Concentration-Time Curve From Time 0 to 72 Hours Postdose for Ixazomib
NCT00932698 (14) [back to overview]AUC(0-72): Area Under the Plasma Concentration-Time Curve From Time 0 to 72 Hours Postdose for Ixazomib
NCT00963820 (11) [back to overview]Accumulation Ratio: Day 15 AUC0-168 / Day 1 AUC0-168 for MLN2238
NCT00963820 (11) [back to overview]Overall Response to Treatment With Ixazomib Citrate Based on Investigator's Evaluation Over Time
NCT00963820 (11) [back to overview]Number of Participants Reporting One or More Treatment-Emergent Adverse Events and Serious Adverse Events
NCT00963820 (11) [back to overview]Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for MLN2238
NCT00963820 (11) [back to overview]Neurotoxicity Grading
NCT00963820 (11) [back to overview]Cmax: Maximum Observed Plasma Concentration for MLN2238
NCT00963820 (11) [back to overview]AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for MLN2238
NCT00963820 (11) [back to overview]Terminal Phase Elimination Half-life (T1/2) for MLN2238
NCT00963820 (11) [back to overview]Terminal Elimination Rate Constant (λz) for MLN2238
NCT00963820 (11) [back to overview]TEmax: Time of Occurrence of Emax
NCT00963820 (11) [back to overview]Emax: Maximum Inhibition
NCT01217957 (18) [back to overview]Phase 1: Recommended Phase 2 Dose of Ixazomib Given in Combination With Lenalidomide and Low-Dose Dexamethasone
NCT01217957 (18) [back to overview]Phase 2: 1 Year Survival Rate
NCT01217957 (18) [back to overview]Phase 2: Duration of Response (DOR)
NCT01217957 (18) [back to overview]Phase 2: Objective Response Rate (ORR) Following Treatment With the Combination Of Oral Ixazomib, Lenalidomide And Low-Dose Dexamethasone
NCT01217957 (18) [back to overview]Phase 2: Overall Response Rate (ORR)
NCT01217957 (18) [back to overview]Phase 2: Overall Survival (OS)
NCT01217957 (18) [back to overview]Phase 2: Progression Free Survival (PFS)
NCT01217957 (18) [back to overview]Phase 2: Time to Best Response
NCT01217957 (18) [back to overview]Phase 2: Time to Progression (TTP)
NCT01217957 (18) [back to overview]Phase 1: AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for Ixazomib
NCT01217957 (18) [back to overview]Phase 1: Cmax: Maximum Observed Plasma Concentration for Ixazomib
NCT01217957 (18) [back to overview]Phase 2: Percentage of Participants With Grade 3 or Higher AEs, SAEs and Treatment Discontinuation
NCT01217957 (18) [back to overview]Phase 2: Percentage of Participants With Complete Response (CR), Stringent Complete Response (sCR), Very Good Partial Response (VGPR), Near Complete Response (nCR), Partial Response (PR) and Minimal Response (MR)
NCT01217957 (18) [back to overview]Phase 2: Percentage of Participants With Complete Response (CR) and Very Good Partial Response (VGPR)
NCT01217957 (18) [back to overview]Phase 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability
NCT01217957 (18) [back to overview]Phase 1: Rac: Accumulation Ratio of Ixazomib
NCT01217957 (18) [back to overview]Phase 1: Maximum Tolerated Dose (MTD) of Ixazomib Administered Weekly in Combination With Lenalidomide and Low-Dose Dexamethasone
NCT01217957 (18) [back to overview]Phase 1: Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for Ixazomib
NCT01318902 (27) [back to overview]Number of Participants With Best Hematologic Response to Treatment Based on Investigators Assessment
NCT01318902 (27) [back to overview]Cmax: Maximum Observed Plasma Concentration for Ixazomib
NCT01318902 (27) [back to overview]Number of Participants With Best Organ Response to Treatment Based on Investigators Assessment
NCT01318902 (27) [back to overview]Ctrough: Plasma Concentration Immediately Prior to Dosing for Ixazomib
NCT01318902 (27) [back to overview]Emax: Maximum Observed Percent Inhibition of Whole Blood 20S Proteasome
NCT01318902 (27) [back to overview]Organ Disease Progression-Free Survival (PFS)
NCT01318902 (27) [back to overview]Number of Participants With Peripheral Neuropathy Reported as a TEAE
NCT01318902 (27) [back to overview]Percentage of Participants With One Year Hematologic Disease PFS
NCT01318902 (27) [back to overview]Recommended Phase 2 Dose (RP2D) of Ixazomib
NCT01318902 (27) [back to overview]Time to First Hematologic Response
NCT01318902 (27) [back to overview]Time to Hematologic Disease Progression
NCT01318902 (27) [back to overview]Time to Organ Disease Progression
NCT01318902 (27) [back to overview]AUC0-168: Area Under the Plasma Concentration-time Curve From Time 0 to 168 Hours Post-dose for Ixazomib
NCT01318902 (27) [back to overview]Number of Participants With Clinically Significant Abnormal Laboratory Values Reported as TEAE
NCT01318902 (27) [back to overview]Ctrough: Plasma Concentration Immediately Prior to Dosing for Ixazomib
NCT01318902 (27) [back to overview]AUC0-168: Area Under the Plasma Concentration-time Curve From Time 0 to 168 Hours Post-dose for Ixazomib
NCT01318902 (27) [back to overview]Tmax: Time of First Occurrence of Cmax for Ixazomib
NCT01318902 (27) [back to overview]Tmax: Time of First Occurrence of Cmax for Ixazomib
NCT01318902 (27) [back to overview]AUE0-168: Area Under Effect Curve of Whole Blood 20S Proteasome Inhibition From Zero to Concentration at 168 Hours for Ixazomib
NCT01318902 (27) [back to overview]Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)
NCT01318902 (27) [back to overview]Duration of Hematologic Response
NCT01318902 (27) [back to overview]Cmax: Maximum Observed Plasma Concentration for Ixazomib
NCT01318902 (27) [back to overview]Time to First Organ Response
NCT01318902 (27) [back to overview]Duration of Organ Response
NCT01318902 (27) [back to overview]Hematologic Disease Progression-Free Survival (PFS)
NCT01318902 (27) [back to overview]Maximum Tolerated Dose (MTD) of Ixazomib
NCT01318902 (27) [back to overview]TEmax: Time to Maximum Observed Effect (Emax) of Whole Blood 20S Proteasome Inhibition for Ixazomib
NCT01335685 (27) [back to overview]Terminal Elimination Rate Constant (λz) for Ixazomib (Phase 1)
NCT01335685 (27) [back to overview]Terminal Elimination Rate Constant (λz) for Ixazomib (Phase 1)
NCT01335685 (27) [back to overview]Terminal Elimination Rate Constant (λz) for Ixazomib (Phase 1)
NCT01335685 (27) [back to overview]Terminal Phase Elimination Half-life (T1/2) for Ixazomib (Phase 1)
NCT01335685 (27) [back to overview]Terminal Phase Elimination Half-life (T1/2) for Ixazomib (Phase 1)
NCT01335685 (27) [back to overview]Terminal Phase Elimination Half-life (T1/2) for Ixazomib (Phase 1)
NCT01335685 (27) [back to overview]Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib (Phase 1)
NCT01335685 (27) [back to overview]Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib (Phase 1)
NCT01335685 (27) [back to overview]Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib (Phase 1)
NCT01335685 (27) [back to overview]AUCtau: Area Under the Plasma Concentration-time Curve Over the Dosing Interval for Ixazomib (Phase 1)
NCT01335685 (27) [back to overview]Duration of Response (DOR) (Phase 2)
NCT01335685 (27) [back to overview]Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Ixazomib (Phase 1)
NCT01335685 (27) [back to overview]Overall Response Rate (ORR)
NCT01335685 (27) [back to overview]Overall Survival (Phase 2)
NCT01335685 (27) [back to overview]Progression Free Survival (Phase 2)
NCT01335685 (27) [back to overview]Time to First Response (Phase 2)
NCT01335685 (27) [back to overview]Time to Progression (TTP) (Phase 2)
NCT01335685 (27) [back to overview]Very Good Partial Response (VGPR) or Better Response Rate (Phase 2)
NCT01335685 (27) [back to overview]AUCtau: Area Under the Plasma Concentration-time Curve Over the Dosing Interval for Ixazomib (Phase 1)
NCT01335685 (27) [back to overview]AUCtau: Area Under the Plasma Concentration-time Curve Over the Dosing Interval for Ixazomib (Phase 1)
NCT01335685 (27) [back to overview]Cmax: Maximum Observed Plasma Concentration for Ixazomib (Phase 1)
NCT01335685 (27) [back to overview]Cmax: Maximum Observed Plasma Concentration for Ixazomib (Phase 1)
NCT01335685 (27) [back to overview]Cmax: Maximum Observed Plasma Concentration for Ixazomib (Phase 1)
NCT01335685 (27) [back to overview]Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
NCT01335685 (27) [back to overview]Observed Accumulation Ratio for AUCtau (Rac) (Phase 1)
NCT01335685 (27) [back to overview]Observed Accumulation Ratio for AUCtau (Rac) (Phase 1)
NCT01335685 (27) [back to overview]Observed Accumulation Ratio for AUCtau (Rac) (Phase 1)
NCT01383928 (29) [back to overview]Overall Survival
NCT01383928 (29) [back to overview]Kaplan-Meier Estimate of Percentage of Participants Achieving Survival at Year 1
NCT01383928 (29) [back to overview]Phase 1: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib
NCT01383928 (29) [back to overview]Phase 1: Percentage of Participants Experiencing 1 or More Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs)
NCT01383928 (29) [back to overview]Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAE) Related to Neurotoxicity
NCT01383928 (29) [back to overview]Phase 1: Number of Participants With Markedly Abnormal Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs)
NCT01383928 (29) [back to overview]Phase 1: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
NCT01383928 (29) [back to overview]Phase 1: Cmax: Maximum Plasma Concentration for Ixazomib
NCT01383928 (29) [back to overview]Phase 1: AUC(0-72): Area Under the Plasma Concentration-Time Curve From Time 0 to 72 Hours Postdose for Ixazomib
NCT01383928 (29) [back to overview]Time to Disease Progression (TTP)
NCT01383928 (29) [back to overview]Progression Free Survival (PFS)
NCT01383928 (29) [back to overview]Phase 2: Time to Response
NCT01383928 (29) [back to overview]Phase 2: Percentage of Participants With Very Good Partial Response (VGPR)
NCT01383928 (29) [back to overview]Phase 2: Percentage of Participants With Treatment-Emergent Adverse Events Resulting in Study Drug Discontinuation
NCT01383928 (29) [back to overview]Phase 2: Percentage of Participants With Stringent Complete Response (sCR)
NCT01383928 (29) [back to overview]Phase 2: Duration of Response (DOR)
NCT01383928 (29) [back to overview]Phase 2: Percentage of Participants With Partial Response (PR)
NCT01383928 (29) [back to overview]Phase 2: Percentage of Participants With Overall Response (CR+VGPR+PR)
NCT01383928 (29) [back to overview]Phase 2: Percentage of Participants With Near Complete Response (nCR)
NCT01383928 (29) [back to overview]Phase 2: Percentage of Participants With Minimal Response (MR)
NCT01383928 (29) [back to overview]Phase 2: Percentage of Participants With Grade 3 or Higher Adverse Events
NCT01383928 (29) [back to overview]Phase 2: Percentage of Participants With Complete Response (CR) + Very Good Partial Response (VGPR)
NCT01383928 (29) [back to overview]Phase 2: Percentage of Participants With Complete Response (CR)
NCT01383928 (29) [back to overview]Phase 2: Percentage of Participants Experiencing Serious Adverse Events
NCT01383928 (29) [back to overview]Phase 1: Percentage of Participants With Best Overall Response
NCT01383928 (29) [back to overview]Phase 1: Recommended Phase 2 Dose (RP2D)
NCT01383928 (29) [back to overview]Phase 1: Rac: Accumulation Ratio of Ixazomib
NCT01383928 (29) [back to overview]Phase 2: Percentage of Participants With Complete Response (CR) and Very Good Partial Response (VGPR) After Cycles 4, 8, and 16
NCT01383928 (29) [back to overview]Phase 1: Maximum Tolerated Dose (MTD)
NCT01454076 (7) [back to overview]AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ixazomib
NCT01454076 (7) [back to overview]Cmax: Maximum Observed Plasma Concentration for Ixazomib
NCT01454076 (7) [back to overview]Number of Participants With Clinically Significant Vital Sign Abnormalities
NCT01454076 (7) [back to overview]Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib
NCT01454076 (7) [back to overview]Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
NCT01454076 (7) [back to overview]Number of Participants With Clinically Significant TEAEs Related to Laboratory Abnormalities
NCT01454076 (7) [back to overview]Percentage of Participants With Best Overall Response
NCT01564537 (18) [back to overview]Number of Participants With Change From Baseline in Pain Response
NCT01564537 (18) [back to overview]Plasma Concentration Over Time for Ixazomib
NCT01564537 (18) [back to overview]Plasma Concentration Over Time for Ixazomib
NCT01564537 (18) [back to overview]Duration of Response (DOR)
NCT01564537 (18) [back to overview]OS in High-Risk Participants
NCT01564537 (18) [back to overview]Overall Response Rate (ORR) as Assessed by the IRC
NCT01564537 (18) [back to overview]Overall Response Rate in Participants Defined by Polymorphism
NCT01564537 (18) [back to overview]Overall Survival (OS)
NCT01564537 (18) [back to overview]Overall Survival in High-Risk Participants Carrying Deletion 17 [Del(17)]
NCT01564537 (18) [back to overview]Percentage of Participants With Complete Response (CR) and Very Good Partial Response (VGPR) as Assessed by the IRC
NCT01564537 (18) [back to overview]PFS in High-Risk Participants
NCT01564537 (18) [back to overview]Progression Free Survival (PFS) as Assessed by the Independent Review Committee (IRC)
NCT01564537 (18) [back to overview]Time to Progression (TTP) as Assessed by the IRC
NCT01564537 (18) [back to overview]Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) Questionnaire (EORTC-QLQ-C30)
NCT01564537 (18) [back to overview]Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) Questionnaire (EORTC-QLQ-C30)
NCT01564537 (18) [back to overview]Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Multiple Myeloma Module (QLQ-MY-20)
NCT01564537 (18) [back to overview]Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Multiple Myeloma Module (QLQ-MY-20)
NCT01564537 (18) [back to overview]Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
NCT01645930 (12) [back to overview]Cmax: Maximum Observed Plasma Concentration for Ixazomib
NCT01645930 (12) [back to overview]Duration of Response (DOR)
NCT01645930 (12) [back to overview]Number of Participants With Dose Limiting Toxicities (DLTs)
NCT01645930 (12) [back to overview]Percentage of Participants With Confirmed Best Response Category
NCT01645930 (12) [back to overview]Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib
NCT01645930 (12) [back to overview]Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib
NCT01645930 (12) [back to overview]Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
NCT01645930 (12) [back to overview]Number of Participants With Clinically Significant Laboratory Abnormalities Reported as Adverse Events of ≥Grade 3 Intensity
NCT01645930 (12) [back to overview]Number of Participants With Clinically Significant Vital Signs Reported as Adverse Events
NCT01645930 (12) [back to overview]AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for Ixazomib
NCT01645930 (12) [back to overview]AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for Ixazomib
NCT01645930 (12) [back to overview]Cmax: Maximum Observed Plasma Concentration for Ixazomib
NCT01659658 (21) [back to overview]Change From Baseline in SF-36 Physical Component Summary Score at Week 28 of the PFS Follow-up
NCT01659658 (21) [back to overview]Duration of Hematologic Response
NCT01659658 (21) [back to overview]EuroQol 5-Dimension 3-Level (EQ-5D-3L) Visual Analogue Scale Score
NCT01659658 (21) [back to overview]Hematologic Disease Progression Free Survival
NCT01659658 (21) [back to overview]Number of Hospitalizations
NCT01659658 (21) [back to overview]Change From Baseline in 36-item Short Form General Health Survey (SF-36) Mental Component Summary Score at Week 28 of the PFS Follow-up
NCT01659658 (21) [back to overview]2-Year Vital Organ (Heart or Kidney) Deterioration and Mortality Rate
NCT01659658 (21) [back to overview]Plasma Concentration of Ixazomib
NCT01659658 (21) [back to overview]Vital Organ Progression Free Survival
NCT01659658 (21) [back to overview]Number of Participants in Each Category of the EuroQol 5-Dimensional (EQ-5D) Questionnaire Score
NCT01659658 (21) [back to overview]Time to Vital Organ (Heart or Kidney) Deterioration and Mortality Rate
NCT01659658 (21) [back to overview]Time To Treatment Failure (TTF)
NCT01659658 (21) [back to overview]Time To Subsequent Anticancer Treatment
NCT01659658 (21) [back to overview]Progression Free Survival (PFS)
NCT01659658 (21) [back to overview]Percentage of Participants With Overall Hematologic Response
NCT01659658 (21) [back to overview]Percentage of Participants With Complete Hematologic Response
NCT01659658 (21) [back to overview]Percentage of Participants With Best Vital Organ (Cardiac and/or Kidney) Response
NCT01659658 (21) [back to overview]Overall Survival
NCT01659658 (21) [back to overview]Number of Participants With Serious Adverse Events (SAEs)
NCT01659658 (21) [back to overview]Change From Baseline in Amyloidosis Symptom Scale Total Score at Week 28 of the PFS Follow-up
NCT01659658 (21) [back to overview]Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) Score at Week 28 of the PFS Follow-up
NCT01830816 (6) [back to overview]Number of Participants With Adverse Events
NCT01830816 (6) [back to overview]Unbound Cmax: Unbound Maximum Observed Plasma Concentration for Ixazomib
NCT01830816 (6) [back to overview]Unbound AUClast: Unbound Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ixazomib
NCT01830816 (6) [back to overview]Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib
NCT01830816 (6) [back to overview]Percentage of Participants With Overall Response (OR) in Relapsed/Refractory Multiple Myeloma (RRMM) Participants
NCT01830816 (6) [back to overview]Duration of Response (DOR) in RRMM Participants
NCT01850524 (20) [back to overview]Pain Response Rate as Assessed by the Brief Pain Inventory- Short Form (BPI-SF) and Analgesic Use
NCT01850524 (20) [back to overview]Overall Response Rate (ORR)
NCT01850524 (20) [back to overview]OS in High-risk Population Carrying Del(17p), t(4;14), or t(14;16) Mutations
NCT01850524 (20) [back to overview]Duration of Response
NCT01850524 (20) [back to overview]Complete Response (CR) Rate
NCT01850524 (20) [back to overview]Percentage of Participants With MRD-Negative Status as Assessed by Flow Cytometry
NCT01850524 (20) [back to overview]Percentage of Participants With New or Worsening of Existing Skeletal-related Events (SREs)
NCT01850524 (20) [back to overview]PFS in High-risk Population Carrying Del(17p), t(4;14), or t(14;16) Mutations
NCT01850524 (20) [back to overview]Progression Free Survival (PFS)
NCT01850524 (20) [back to overview]Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
NCT01850524 (20) [back to overview]Progression Free Survival (PFS)-2
NCT01850524 (20) [back to overview]Time to Pain Progression
NCT01850524 (20) [back to overview]Time to Progression (TTP)
NCT01850524 (20) [back to overview]Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs)
NCT01850524 (20) [back to overview]Time to Response
NCT01850524 (20) [back to overview]Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score
NCT01850524 (20) [back to overview]Change From Baseline in HRQOL Measured by EORTC-QLQ-MY20 Scale
NCT01850524 (20) [back to overview]Cmax: Maximum Plasma Concentration for Ixazomib
NCT01850524 (20) [back to overview]Overall Survival (OS)
NCT01850524 (20) [back to overview]Number of Participants With Shifts From Baseline to Worst Value in Eastern Cooperative Oncology Group (ECOG) Performance Score
NCT01864018 (7) [back to overview]Number of Patients Experiencing a Grade 3 or Greater Adverse Event at Least Possibly Related to Treatment as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
NCT01864018 (7) [back to overview]Maximum Tolerated (MTD) Dose of Cyclophosphamide (Phase I)
NCT01864018 (7) [back to overview]Rate of Complete Response, Very Good Partial Response, or Partial Response (Phase II, Cohort B)
NCT01864018 (7) [back to overview]Progression-free Survival (PFS)
NCT01864018 (7) [back to overview]Maximum Tolerated (MTD) Dose of Cyclophosphamide With Ixazomib and Dexamethasone (Phase I)
NCT01864018 (7) [back to overview]Survival Time
NCT01864018 (7) [back to overview]Percentage of Patients With Complete Response or Very Good Partial Response (Phase II, Cohort A)
NCT01887587 (2) [back to overview]Optimal Dose of MLN9708
NCT01887587 (2) [back to overview]Adverse Events.
NCT01912222 (6) [back to overview]Number of Participants Reporting Clinically Significant Change From Baseline in Laboratory Values
NCT01912222 (6) [back to overview]Unbound Cmax: Unbound Maximum Observed Plasma Concentration for Ixazomib
NCT01912222 (6) [back to overview]Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) and Serious Adverse Events (SAE)
NCT01912222 (6) [back to overview]Tmax- Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib
NCT01912222 (6) [back to overview]Number of Participants Reporting Clinically Significant Change From Baseline in Vital Signs
NCT01912222 (6) [back to overview]Unbound AUC(0-last): Unbound Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ixazomib
NCT01939899 (11) [back to overview]Number of Participants With Overall Response Rate (ORR)
NCT01939899 (11) [back to overview]Duration of Response (DOR)
NCT01939899 (11) [back to overview]Lead-in Dose Finding Phase: Recommended Phase 2 Dose (RP2D)
NCT01939899 (11) [back to overview]Phase 2: Number of Participants With Response Rates in PSMB1 Positive and PSMB1 Negative
NCT01939899 (11) [back to overview]Phase 2: Rate of Disease Control
NCT01939899 (11) [back to overview]Progression Free Survival (PFS)
NCT01939899 (11) [back to overview]Time to Response (TTR)
NCT01939899 (11) [back to overview]Lead-in Dose Finding Phase: AUC(0-168): Area Under the Plasma Concentration-time Curve From Time 0 to 168 Hours Postdose for Ixazomib
NCT01939899 (11) [back to overview]Lead-in Dose Finding Phase: Cmax: Maximum Observed Plasma Concentration for Ixazomib
NCT01939899 (11) [back to overview]Lead-in Dose Finding Phase: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib
NCT01939899 (11) [back to overview]Number of Participants Experiencing 1 or More Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
NCT01953783 (19) [back to overview]Ixazomib and Metabolites as Percent of Total Radioactivity in Plasma
NCT01953783 (19) [back to overview]Ixazomib and Metabolites as Percent of Total Dose Administered in Urine
NCT01953783 (19) [back to overview]Ixazomib and Metabolites as Percent of Total Dose Administered in Feces
NCT01953783 (19) [back to overview]Part A: Tmax: Time to Reach the Maximum Observed Whole Blood Concentration (Cmax) for TRA
NCT01953783 (19) [back to overview]Part A: Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for Ixazomib
NCT01953783 (19) [back to overview]Part A: Renal Clearance of Ixazomib
NCT01953783 (19) [back to overview]Part A: Cumulative Percentage of the Total Radioactivity Dose Excreted in Urine
NCT01953783 (19) [back to overview]Part A: Tmax: Time to Reach the Cmax for TRA
NCT01953783 (19) [back to overview]Part A: Cumulative Percentage of the Total Radioactivity Dose Excreted in Feces
NCT01953783 (19) [back to overview]Part A: Cumulative Percentage of Ixazomib Dose Recovered in the Urine
NCT01953783 (19) [back to overview]Part A: Cmax: Maximum Observed Plasma Concentration of TRA
NCT01953783 (19) [back to overview]Part A: Cmax: Maximum Observed Plasma Concentration for Ixazomib
NCT01953783 (19) [back to overview]Part A: AUC(0-816): Area Under the Whole Blood Concentration-time Curve From Time 0 to 816 Hrs Post-dose for TRA
NCT01953783 (19) [back to overview]Part A: AUC(0-816): Area Under the Plasma Concentration-time Curve From Time 0 to 816 Hrs Post-dose for TRA
NCT01953783 (19) [back to overview]Part A: Cmax: Maximum Observed Whole Blood Concentration of TRA
NCT01953783 (19) [back to overview]Part A: AUC(0-312): Area Under the Plasma Concentration-time Curve From Time 0 to 312 Hrs Post-dose for Ixazomib
NCT01953783 (19) [back to overview]Number of Participants With TEAEs Related to Vital Signs
NCT01953783 (19) [back to overview]Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
NCT01953783 (19) [back to overview]Number of Participants With TEAEs Related to Investigations System Organ Class for Laboratory Values
NCT02004275 (13) [back to overview]Progression Free Survival (PFS) for All Patients on the Pomalidomide/Dexamethasone Arm at the Time of Cross-over to Pomalidomide/Dexamethasone/Ixazomib (Phase II)
NCT02004275 (13) [back to overview]Overall Response Rate (ORR)
NCT02004275 (13) [back to overview]Response Rates (Overall Response Rate (ORR), Clinical Benefit Rate (CBR), Disease Control Rate (DCR) for All Patients on the Pomalidomide/Dexamethasone Arm at the Time of Cross-over to Pomalidomide/Dexamethasone/Ixazomib (Phase II)
NCT02004275 (13) [back to overview]Baseline Level of Perceived Fatigue and QOL, Assessed Using the Registration Fatigue/Uniscale Assessment Form (Phase II)
NCT02004275 (13) [back to overview]Progression Free Survival (PFS) (Phase II)
NCT02004275 (13) [back to overview]Overall Survival (OS) (Phase II)
NCT02004275 (13) [back to overview]Maximum Tolerated Dose (MTD) of Pomalidomide and Ixazomib, Determined According to Incidence of Dose Limiting Toxicity (DLT) Graded Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (Phase I)
NCT02004275 (13) [back to overview]Incidence, Type and Severity of Adverse Events, Graded According to National Cancer Institute (NCI) Common Terminology Criteria Adverse Events (CTCAE) Version 4.0 (Phase II)
NCT02004275 (13) [back to overview]Incidence of Dose Reductions/Delays (Phase I)
NCT02004275 (13) [back to overview]Incidence and Type of Dose Limiting Toxicities (DLTs) Graded According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (Phase I)
NCT02004275 (13) [back to overview]Duration of Response (DOR), Calculated for All Patients Achieving an Objective Response, Partial Response (PR) or Better (Phase II)
NCT02004275 (13) [back to overview]Disease Control Rate (DCR), Defined as Stable Disease (SD) and Better According to International Myeloma Working Group (IMWG) Uniform Response Criteria (Phase II)
NCT02004275 (13) [back to overview]Clinical Benefit Rate (CBR)
NCT02030405 (3) [back to overview]Overall Survival (OS)
NCT02030405 (3) [back to overview]Serious Adverse Events Related to Ixazomib
NCT02030405 (3) [back to overview]Overall Response Rate (ORR)
NCT02046070 (25) [back to overview]Tmax: Time to First Occurrence of Cmax for Ixazomib in RRMM Participants
NCT02046070 (25) [back to overview]Percentage of Participants With CR + VGR + PR (ORR), CR, VGPR, and PR in NDMM Participants Remaining on Treatment After 13 Cycles
NCT02046070 (25) [back to overview]Combined Response Rate During the Induction Phase in Newly Diagnosed Multiple Myeloma (NDMM) Participants
NCT02046070 (25) [back to overview]Duration of Response (DOR) in NDMM Participants
NCT02046070 (25) [back to overview]Duration of Response (DOR) in RRMM Participants
NCT02046070 (25) [back to overview]Tmax: Time to First Occurrence of Cmax for Ixazomib in NDMM Participants
NCT02046070 (25) [back to overview]Percentage of Participants With CR + VGPR + PR (ORR), CR, VGPR, PR and Stable Disease (SD), Progressive Disease (PD) During the Induction Phase
NCT02046070 (25) [back to overview]Overall Response Rate (ORR) in Relapsed and/or Refractory Multiple Myeloma (RRMM) Participants
NCT02046070 (25) [back to overview]AUCtau: Area Under the Concentration-time Curve During a Dosing Interval for Ixazomib in NDMM Participants
NCT02046070 (25) [back to overview]Progression Free Survival (PFS) in NDMM Participants
NCT02046070 (25) [back to overview]Progression Free Survival (PFS) in RRMM Participants
NCT02046070 (25) [back to overview]Time to Progression (TTP) in NDMM Participants
NCT02046070 (25) [back to overview]Time to Progression (TTP) in RRMM Participants
NCT02046070 (25) [back to overview]Time to Response (TTR) in NDMM Participants During the Induction Phase
NCT02046070 (25) [back to overview]AUCtau: Area Under the Concentration-time Curve During a Dosing Interval for Ixazomib in RRMM Participants
NCT02046070 (25) [back to overview]Change From Baseline in EORTC Quality of Life Questionnaire (QLQ-C30) in RRMM Participants
NCT02046070 (25) [back to overview]Time to Response (TTR) in RRMM Participants
NCT02046070 (25) [back to overview]Cmax: Maximum Observed Plasma Concentration for Ixazomib in NDMM Participants
NCT02046070 (25) [back to overview]Cmax: Maximum Observed Plasma Concentration for Ixazomib in RRMM Participants
NCT02046070 (25) [back to overview]Number of Participants With Adverse Events (AEs), Grade 3 or Higher AEs, AEs Resulting in Treatment Discontinuation, AEs Resulting in Dose Reduction and Serious Adverse Events (SAEs) in NDMM Participants
NCT02046070 (25) [back to overview]Number of Participants With AEs, Grade 3 or Higher AEs, AEs Resulting in Treatment Discontinuation, AEs Resulting in Dose Reduction, SAEs in RRMM Participants
NCT02046070 (25) [back to overview]Number of Participants With AEs, SAEs, AEs Resulting in Discontinuation and AEs Resulting in Dose Reduction in NDMM Participants Remaining on Treatment After 13 Cycles
NCT02046070 (25) [back to overview]Percentage of Participants With (CR + VGPR), CR, VGPR, PR, SD and PD in RRMM Participants
NCT02046070 (25) [back to overview]Percentage of Participants With CR + VGPR + PR (ORR), CR + VGPR, CR, VGPR, PR, SD and PD Throughout the Entire Treatment Period in NDMM Participants
NCT02046070 (25) [back to overview]Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) During the Induction Phase in NDMM Participants
NCT02057640 (4) [back to overview]Response to Combination Therapy (Panobinostat, Dexamethasone, MLN9708)
NCT02057640 (4) [back to overview]Overall Survival
NCT02057640 (4) [back to overview]Number of Participants With Dose Limiting Toxicity According to CTCAE Version 4.03
NCT02057640 (4) [back to overview]Progression-free Survival
NCT02119468 (7) [back to overview]Overall Response Rate at the Recommended Phase II Dose (RP2D)
NCT02119468 (7) [back to overview]Clinical Benefit Response Rate at the Recommended Phase II Dose (RP2D)
NCT02119468 (7) [back to overview]Duration of Response at the Recommended Phase II Dose (RP2D)
NCT02119468 (7) [back to overview]Maximum Tolerated Dose (MTD) of MLN9708 (Phase I)
NCT02119468 (7) [back to overview]Number of Patients With Dose-Limiting Toxicities (Phase I)
NCT02119468 (7) [back to overview]One-Year Overall Survival at the Recommended Phase II Dose (RP2D)
NCT02119468 (7) [back to overview]One-Year Progression-Free Survival at the Recommend Phase II Dose (RP2D)
NCT02158975 (5) [back to overview]Median Overall Survival Time
NCT02158975 (5) [back to overview]Median Progression Free Survival Time
NCT02158975 (5) [back to overview]Objective Response Rate
NCT02158975 (5) [back to overview]Number Patients That Experience Adverse Events, Grades 3-5
NCT02158975 (5) [back to overview]Duration of Response
NCT02168101 (6) [back to overview]Number of Participants With Incidence of Chronic Graft-versus-host Disease (cGVHD) After Receiving Allogeneic Stem Cell Transplant and Maintenance With MLN9708
NCT02168101 (6) [back to overview]Median Overall Survival (OS) at 2 Years Post-allogeneic Stem Cell Transplant (ASCT)
NCT02168101 (6) [back to overview]Number of Phase I Patients Receiving 2.3mg, 3mg, or 4mg MLN9708 Experiencing a Dose-Limiting Toxicity (DLT) to Determine the Maximum Tolerated Dose
NCT02168101 (6) [back to overview]Median Progression-Free Survival (PFS) at 2 Years Post-maintenance Therapy
NCT02168101 (6) [back to overview]Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety of MLN9708 When Used as Maintenance After Allogeneic Stem Cell Transplant for Multiple Myeloma Multiple Myeloma
NCT02168101 (6) [back to overview]Number of Participants With Incidence of Acute Graft-versus-host Disease (aGVHD) After Receiving Allogeneic Stem Cell Transplant and Maintenance With MLN9708
NCT02169791 (6) [back to overview]Time to Platelet Recovery Post Transplant
NCT02169791 (6) [back to overview]Number of Participants Experiencing Relapse or Progression
NCT02169791 (6) [back to overview]Neutrophil Engraftment
NCT02169791 (6) [back to overview]Graft Versus Host Disease
NCT02169791 (6) [back to overview]Day 30 CD33 Donor Chimerism
NCT02169791 (6) [back to overview]Day 30 CD3 Donor Chimerism
NCT02176486 (10) [back to overview]Change From Baseline in Complement Protein C3 and C4 at Day 84
NCT02176486 (10) [back to overview]Percentage of Participants Who Experienced at Least One AE Leading to Study Drug Discontinuation
NCT02176486 (10) [back to overview]Percentage of Participants Who Experienced at Least One Grade Greater Than or Equal to (>=) 2 Treatment Emergent Adverse Event (TEAE)
NCT02176486 (10) [back to overview]Percentage of Participants Who Experienced at Least One Treatment Emergent Serious Adverse Event (SAE)
NCT02176486 (10) [back to overview]Percentage of Participants With at Least One Markedly Abnormal Value (MAV) for Hematologic Parameters
NCT02176486 (10) [back to overview]Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Day 84
NCT02176486 (10) [back to overview]Plasma Concentrations of Ixazomib at Each Scheduled Collection Time
NCT02176486 (10) [back to overview]Change From Baseline in Levels of Autoantibodies (Anti-double-stranded Deoxyribonucleic Acid [dsDNA]) at Day 84
NCT02176486 (10) [back to overview]Change From Baseline in Urine Protein to Creatinine Ratio (UPCR) at Day 84
NCT02176486 (10) [back to overview]Change From Baseline in Serum Creatinine (sCR) Level at Day 84
NCT02181413 (1) [back to overview]Progression Free Survival (PFS)
NCT02250300 (3) [back to overview]Number of Participants Experiencing Dose-limiting Toxicity of MLN9708
NCT02250300 (3) [back to overview]Maximum-tolerated Dose of MLN9708.
NCT02250300 (3) [back to overview]Cumulative Incidence of Chronic Graft-versus-host Disease.
NCT02253316 (6) [back to overview]MRD-negative Rate After ASCT
NCT02253316 (6) [back to overview]Response Rate of IRD Consolidation
NCT02253316 (6) [back to overview]Number of Participants With Improvement in Minimal Residual Disease (MRD)
NCT02253316 (6) [back to overview]Compare Response Rate Between the Two Maintenance Arms
NCT02253316 (6) [back to overview]Toxicity of IRD Consolidation
NCT02253316 (6) [back to overview]Rate of MRD-positive to MRD-negative Conversion Between the Two Maintenance Arms
NCT02302846 (1) [back to overview]Relapse-Free Survival (RFS)
NCT02312258 (21) [back to overview]Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status
NCT02312258 (21) [back to overview]Time to Resolution of Peripheral Neuropathy (PN) Events
NCT02312258 (21) [back to overview]Time to Progression (TTP)
NCT02312258 (21) [back to overview]Time to Next Line Therapy (TTNT)
NCT02312258 (21) [back to overview]Time to Improvement of PN Events
NCT02312258 (21) [back to overview]Time to End of the Next-line of Therapy After Study Treatment
NCT02312258 (21) [back to overview]Progression Free Survival 2 (PFS2)
NCT02312258 (21) [back to overview]Progression Free Survival (PFS)
NCT02312258 (21) [back to overview]PFS in a High-risk Population
NCT02312258 (21) [back to overview]Percentage of Participants With Conversion From Minimal Residual Disease (MRD) Positive to MRD Negative
NCT02312258 (21) [back to overview]Percentage of Participants Who Develop a New Primary Malignancy
NCT02312258 (21) [back to overview]Overall Survival (OS)
NCT02312258 (21) [back to overview]OS in a High-risk Population
NCT02312258 (21) [back to overview]Duration of Next-line Therapy
NCT02312258 (21) [back to overview]Percentage of Participants Who Achieve or Maintain Any Best Response Category During the Treatment Period
NCT02312258 (21) [back to overview]Correlation of MRD Status With PFS and OS
NCT02312258 (21) [back to overview]Correlation Between Frailty Status and PFS and OS
NCT02312258 (21) [back to overview]Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) as Measured by the Global Health Status (GHS)
NCT02312258 (21) [back to overview]Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status
NCT02312258 (21) [back to overview]Pharmacokinetic Parameter: Plasma Concentration of Ixazomib
NCT02312258 (21) [back to overview]Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
NCT02400437 (7) [back to overview]Time to Progression (TTP)
NCT02400437 (7) [back to overview]Progression-free Survival (PFS)
NCT02400437 (7) [back to overview]Very Good Partial Response Rate (VGPR) for IDR
NCT02400437 (7) [back to overview]Time to Next Therapy (TTNT)
NCT02400437 (7) [back to overview]Duration of Response (DOR)
NCT02400437 (7) [back to overview]Overall Response Rate
NCT02400437 (7) [back to overview]Overall Response Rate by MYD88 L265P and CXCR4-WHIM Status
NCT02412228 (2) [back to overview]Evaluation of the Toxicities Associated With Ixazomib With Metronomic Cyclophosphamide and Dexamethasone.
NCT02412228 (2) [back to overview]Evaluation of the Response Rate of Ixazomib With Metronomic Cyclophosphamide and Dexamethasone for First-line Treatment of Multiple Myeloma.
NCT02440464 (14) [back to overview]Percentage of Participants With Progression-Free Survival
NCT02440464 (14) [back to overview]Percentage of Participants With Infections Post-randomization by Time Point
NCT02440464 (14) [back to overview]Percentage of Participants With Infections Post-randomization by Infection Type
NCT02440464 (14) [back to overview]Percentage of Participants With Best Response to Treatment After Randomization
NCT02440464 (14) [back to overview]Percentage of Participants With Treatment-Related Mortality (TRM)
NCT02440464 (14) [back to overview]Percentage of Participants With Overall Survival (OS)
NCT02440464 (14) [back to overview]Percentage of Participants With Toxicities Post-randomization by Time Point
NCT02440464 (14) [back to overview]Percentage of Participants With Toxicities Post-randomization by Toxicity Type
NCT02440464 (14) [back to overview]Percentage of Participants With Response to Treatment
NCT02440464 (14) [back to overview]Percentage of Participants With Chronic GVHD
NCT02440464 (14) [back to overview]Medical Outcomes Study (MOS) - Short Form 36 (SF-36) Score
NCT02440464 (14) [back to overview]Percentage of Participants With Acute GVHD (Grades III-IV)
NCT02440464 (14) [back to overview]Percentage of Participants With Disease Progression
NCT02440464 (14) [back to overview]Functional Assessment of Cancer Therapy (FACT) - Bone Marrow Transplant (BMT) Total Score
NCT02477215 (7) [back to overview]Overall Survival (OS)
NCT02477215 (7) [back to overview]Progression Free Survival (PFS)
NCT02477215 (7) [back to overview]Cumulative Response Rates in Patients After Eight Cycles.
NCT02477215 (7) [back to overview]Duration of Response (DoR)
NCT02477215 (7) [back to overview]Maximum Tolerated Dose of Bendamustine
NCT02477215 (7) [back to overview]Number of Participants Experiencing Dose-Limiting Toxicity (DLT)
NCT02477215 (7) [back to overview]Objective Response Rate
NCT02481310 (2) [back to overview]12-month PFS (Progression Free Survival) of Treatment With Ixazomib in Combination With DA-EPOCH-R (Phase II)
NCT02481310 (2) [back to overview]To Determine the Recommended Phase II Dose (RP2D) of Ixazomib in Combination With DA-EPOCH-R.
NCT02499081 (1) [back to overview]Change in Serum Osteocalcin From Baseline to End of Study in Patients With Relapsed/Refractory Multiple Myeloma.
NCT02513498 (15) [back to overview]Incidence of Discontinuation of All Systemic Immune Suppressive Therapies
NCT02513498 (15) [back to overview]Biologic Studies
NCT02513498 (15) [back to overview]Cumulative Incidence of Primary Malignancy Relapse
NCT02513498 (15) [back to overview]Probability of Failure-free Survival at 1 Year
NCT02513498 (15) [back to overview]Probability of Non-relapse Mortality at 1 Year
NCT02513498 (15) [back to overview]Probability of Overall Survival at 1 Year
NCT02513498 (15) [back to overview]Probability of Treatment Failure at 6 Months
NCT02513498 (15) [back to overview]Treatment Success
NCT02513498 (15) [back to overview]Use of Additional Systemic Immune Suppressive Therapies
NCT02513498 (15) [back to overview]Incidence of Adverse Events
NCT02513498 (15) [back to overview]Overall Response Rate (ORR) (Complete Response + Partial Response)
NCT02513498 (15) [back to overview]Symptoms as Measured by Patient Self-report--Lee Chronic GVHD Symptom Scale
NCT02513498 (15) [back to overview]Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36)
NCT02513498 (15) [back to overview]Symptoms as Measured by Patient Self-report--Functional Assessment of Chronic Illness Therapy (FACT)
NCT02513498 (15) [back to overview]Symptoms as Measured by Patient Self-report--Human Activities Profile (HAP)
NCT02547662 (5) [back to overview]Extramedullary Response Rate
NCT02547662 (5) [back to overview]Confirmed Response Rate
NCT02547662 (5) [back to overview]Incidence of Adverse Events Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
NCT02547662 (5) [back to overview]Biochemical Response Rate
NCT02547662 (5) [back to overview]Progression-free Survival
NCT02619682 (3) [back to overview]Number of Participants With Adverse Events, Graded According to CTCAE Version 4.0
NCT02619682 (3) [back to overview]Overall Survival
NCT02619682 (3) [back to overview]Disease Free Survival
NCT02630030 (3) [back to overview]Number of Patients With Safety and Tolerability of Ixazomib
NCT02630030 (3) [back to overview]Number of Participants With Treatment-Emergent Adverse Events
NCT02630030 (3) [back to overview]Concentration of Ixazomib in Tumor Tissue
NCT02633059 (8) [back to overview]Incidence of Adverse Events Graded According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 (Phase II)
NCT02633059 (8) [back to overview]Overall Survival (Phase II)
NCT02633059 (8) [back to overview]Progression Free Survival (Phase II)
NCT02633059 (8) [back to overview]Rate of Complete Response (CR) (Phase II)
NCT02633059 (8) [back to overview]Rate of Partial Response (PR) (Phase II)
NCT02633059 (8) [back to overview]Rate of Confirmed Response, Defined as a Patient Who Has Achieved a Stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR), or Partial Response (PR) on Two Consecutive Evaluations (Phase II)
NCT02633059 (8) [back to overview]The Number of Participants Who Experienced Dose Limiting Toxicities. Maximum Tolerated Dose (MTD) of Ixazomib Citrate and Idasanutlin in Combination With Dexamethasone (Phase I)
NCT02633059 (8) [back to overview]Incidence of Adverse Events Graded According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 (Phase I)
NCT02898259 (7) [back to overview]Duration of Response
NCT02898259 (7) [back to overview]Maximum Tolerated Dose (MTD) of Oral Ixazomib
NCT02898259 (7) [back to overview]Overall Response Rate
NCT02898259 (7) [back to overview]Time to Treatment Failure
NCT02898259 (7) [back to overview]Time to Progression
NCT02898259 (7) [back to overview]Progression Free Survival
NCT02898259 (7) [back to overview]Overall Survival
NCT02917941 (9) [back to overview]Time to Progression (TTP)
NCT02917941 (9) [back to overview]Number of Participants With NCI CTCAE Grade 3 or Higher TEAEs Related to Vital Signs
NCT02917941 (9) [back to overview]Progression-free Survival (PFS)
NCT02917941 (9) [back to overview]Percentage of Participants With Very Good Partial Response (VGPR) or Better Response (Complete Response (CR) + VGPR)
NCT02917941 (9) [back to overview]Overall Survival (OS)
NCT02917941 (9) [back to overview]Overall Response Rate (ORR)
NCT02917941 (9) [back to overview]Number of Participants With One or More Treatment-emergent Adverse Events (TEAEs)
NCT02917941 (9) [back to overview]Number of Participants With NCI CTCAE Grade 3 or Higher TEAEs Related Laboratory Parameters
NCT02917941 (9) [back to overview]Duration of Response (DOR)
NCT02946047 (6) [back to overview]Culturable HIV by Quantitative Viral Outgrowth Assay
NCT02946047 (6) [back to overview]Cell Associated HIV DNA in CD4 T Cell Subsets
NCT02946047 (6) [back to overview]CD4/CD8 Ratio
NCT02946047 (6) [back to overview]Absolute CD8 T Cell Count
NCT02946047 (6) [back to overview]Absolute CD4 T Cell Count
NCT02946047 (6) [back to overview]Incidence of Treatment-Emergent Adverse Events
NCT03169361 (2) [back to overview]Number of Participants Reporting One or More Adverse Events (AEs)
NCT03169361 (2) [back to overview]Number of Participants Who Had One or More Adverse Drug Reactions (ADRs)
NCT03170882 (13) [back to overview]Overall Survival (OS)
NCT03170882 (13) [back to overview]Health Care Utilization (HU): Number of Participants With at Least One Medical Encounter
NCT03170882 (13) [back to overview]Duration of Response (DOR)
NCT03170882 (13) [back to overview]Percentage of Participants With Overall Response
NCT03170882 (13) [back to overview]Time to Progression (TTP)
NCT03170882 (13) [back to overview]HU: Duration of Medical Encounters
NCT03170882 (13) [back to overview]HRQOL Based on EORTC Multiple Myeloma Module 20 (EORTC QLQ-MY20) Score
NCT03170882 (13) [back to overview]Health-Related Quality of Life (HRQOL) Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire- Core 30 (EORTC QLQ-C30) Physical Domain Score
NCT03170882 (13) [back to overview]HRQOL Based on EORTC QLQ-C30 SubScale Score
NCT03170882 (13) [back to overview]Progression Free Survival (PFS)
NCT03170882 (13) [back to overview]Time to Response
NCT03170882 (13) [back to overview]HRQOL Based on EuroQol Visual Analogue Scale (EQ VAS) Score
NCT03170882 (13) [back to overview]Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score
NCT03202628 (5) [back to overview]Number of Patients Experiencing Adverse Events Graded According to the Medical Dictionary for Regulatory Activities (MedDRA) Version (v) 12.1
NCT03202628 (5) [back to overview]Percent of Patients Alive at 30 Months
NCT03202628 (5) [back to overview]Percentage of Participants With Greater Than or Equal to (>=) Very Good Partial Response (VGPR) Rate
NCT03202628 (5) [back to overview]Overall Response Rate
NCT03202628 (5) [back to overview]Progression-free Survival at 18 Months (PFS18) Defined as the Proportion of Patients Alive and Free From Disease Progression at 18 Months From Study Entry
NCT03213158 (11) [back to overview]Change in Circulating APRIL Levels as Assessed by APRIL ELISA Assay
NCT03213158 (11) [back to overview]Safety of Ixazomib as Assesses by Percentage of Participants With Malignancies Within 12 Months
NCT03213158 (11) [back to overview]Safety of Ixazomib: as Assesses by Percentage of Participants With Distal Neuropathy Within 12 Months
NCT03213158 (11) [back to overview]Change in Circulating BAFF Levels as Assessed by BAFF ELISA Assay
NCT03213158 (11) [back to overview]Safety of Ixazomib as Assesses by Percentage of Participants With Thrombocytopenia Within 12 Months
NCT03213158 (11) [back to overview]Safety of Ixazomib as Assesses by Percentage of Participants With Hematological Complications Within 12 Months
NCT03213158 (11) [back to overview]Safety of Ixazomib as Assesses by Percentage of Participants With Gastrointestinal Symptoms Within 12 Months
NCT03213158 (11) [back to overview]Safety of Ixazomib as Assesses by Percentage of Participants With Cardiovascular Complications Within 12 Months
NCT03213158 (11) [back to overview]Safety of Ixazomib as Assesses by Percentage of Participants Caught Infection Within 12 Months
NCT03213158 (11) [back to overview]Efficacy of Ixazomib: Percentage of Participants With > 20 Percent Decline in Calculated Panel Reactive Antibody (cPRA)
NCT03213158 (11) [back to overview]Efficacy of Ixazomib: Percentage of Participants Received Successful Kidney Transplantation Within 12 Months
NCT03416374 (21) [back to overview]Number of Participants With Minimal Residual Disease (MRD) Positive or Negative in Bone Marrow in Participants Who Achieved CR
NCT03416374 (21) [back to overview]Patient-Reported Outcome Health-Related Quality of Life (HRQoL) Based on Global Health Status Scale of European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30)
NCT03416374 (21) [back to overview]Patient-Reported Outcome Health-Related Quality of Life (HRQoL) Based on Global Health Status Scale of European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30)
NCT03416374 (21) [back to overview]Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score
NCT03416374 (21) [back to overview]Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score
NCT03416374 (21) [back to overview]Percentage of Participants Who Achieve or Maintain Any Best Response
NCT03416374 (21) [back to overview]Relative Dose Intensity (RDI)
NCT03416374 (21) [back to overview]Overall Survival (OS) From the Start of Study Treatment
NCT03416374 (21) [back to overview]Healthcare Resource Utilization (HCRU): Duration of Hospital Stay Per Participants
NCT03416374 (21) [back to overview]Duration of Response (DOR)
NCT03416374 (21) [back to overview]Duration of Therapy (DOT)
NCT03416374 (21) [back to overview]Evaluation of Modified Quality-Adjusted Life-Years (QALYs)
NCT03416374 (21) [back to overview]Healthcare Resource Utilization (HCRU): Number of Events With Hospitalization Per Participants-Month
NCT03416374 (21) [back to overview]Percentage of Participants Continuing Treatment With Ixazomib at 12 Months From the Start of Study Treatment
NCT03416374 (21) [back to overview]Percentage of Participants Who Achieved VGPR or Better (CR + VGPR)
NCT03416374 (21) [back to overview]Percentage of Participants With Bone Lesions (Bone Evaluation)
NCT03416374 (21) [back to overview]PFS From the Start of Study Treatment
NCT03416374 (21) [back to overview]Progression-Free Survival (PFS) Rate at 12 Months From the Start of Study Treatment
NCT03416374 (21) [back to overview]Time to Next Treatment (TTNT)
NCT03416374 (21) [back to overview]Number of Participants Reporting One or More Treatment-Emergent AEs (TEAEs)
NCT03416374 (21) [back to overview]Overall Response Rate (ORR)
NCT03433001 (15) [back to overview]Percentage of Participants Who Achieve or Maintain Any Best Response
NCT03433001 (15) [back to overview]Relative Dose Intensity (RDI)
NCT03433001 (15) [back to overview]Patient-Reported Outcome Health-Related Quality of Life (HRQoL) Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30) Global Health Status Score
NCT03433001 (15) [back to overview]Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score
NCT03433001 (15) [back to overview]Percentage of Participants Who Achieve VGPR or Better (CR+VGPR)
NCT03433001 (15) [back to overview]Percentage of Participants With Bone Lesions (Bone Evaluation)
NCT03433001 (15) [back to overview]Progression-Free Survival (PFS)
NCT03433001 (15) [back to overview]Time to Next Treatment (TTNT)
NCT03433001 (15) [back to overview]Rate of Minimal Residual Disease (MRD) Negativity in Bone Marrow in Participants Who Achieved CR
NCT03433001 (15) [back to overview]PFS Rate at 12 Months and 24 Months After the Start of Treatment
NCT03433001 (15) [back to overview]Percentage of Participants Who Continue to Receive Treatment at 12 Months and 24 Months After Start of Treatment
NCT03433001 (15) [back to overview]Overall Survival (OS)
NCT03433001 (15) [back to overview]Overall Response Rate (ORR)
NCT03433001 (15) [back to overview]Number of Participants Reporting One or More Treatment-Emergent AEs (TEAEs)
NCT03433001 (15) [back to overview]Duration of Therapy (DOT)
NCT03439293 (7) [back to overview]Time to Progression (TTP)
NCT03439293 (7) [back to overview]Progression-free Survival (PFS)
NCT03439293 (7) [back to overview]Percentage of Participants With Very Good Partial Response (VGPR) or Better (Complete Response + VGPR)
NCT03439293 (7) [back to overview]Overall Survival (OS)
NCT03439293 (7) [back to overview]Overall Response Rate (ORR)
NCT03439293 (7) [back to overview]Duration of Response (DOR)
NCT03439293 (7) [back to overview]Time To Response (TTR)
NCT03506360 (6) [back to overview]>= Very Good Partial Response (VGPR) Response Percentage With Pembrolizumab Added to Ixazomib Citrate and Dexamethasone
NCT03506360 (6) [back to overview]Complete Response Percentage With Pembrolizumab Added to Ixazomib Citrate and Dexamethasone
NCT03506360 (6) [back to overview]Incidence of Adverse Events
NCT03506360 (6) [back to overview]Overall Response Percentage
NCT03506360 (6) [back to overview]Survival Time
NCT03506360 (6) [back to overview]Progression-free Survival
NCT03770260 (1) [back to overview]Number of Participants Experiencing a Dose Limiting Toxicity (Dose Escalation)
NCT04079738 (1) [back to overview]Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose(s) (RP2D)
NCT04119336 (2) [back to overview]Objective Response Rate (ORR)
NCT04119336 (2) [back to overview]Progression Free Survival
NCT04272775 (8) [back to overview]Number of Participants With Grade 3 or Higher Laboratory Tests Abnormalities
NCT04272775 (8) [back to overview]Number of Participants Who Achieved Complete Response (CR), Very Good Partial Response (VGPR), and Partial Response (PR)
NCT04272775 (8) [back to overview]Number of Participants Who Experienced at Least One Treatment-emergent Adverse Event (TEAE)
NCT04272775 (8) [back to overview]Number of Participants With Grade 3 or Higher TEAE Related to 12-lead Electrocardiograms (ECGs)
NCT04272775 (8) [back to overview]Number of Participants With Grade 3 or Higher TEAE Related to Body Weight
NCT04272775 (8) [back to overview]Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)
NCT04272775 (8) [back to overview]Number of Participants With Grade 3 or Higher TEAE Related to Vital Signs
NCT04272775 (8) [back to overview]Cmax: Maximum Observed Plasma Concentration for Ixazomib

Part 1: AUC (0-72): Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours Post-dose for Ixazomib

AUC (0-72) is a measure of the area under the plasma concentration-time curve from time 0 to 72 hours post-dose for ixazomib. (NCT00830869)
Timeframe: Part 1: Cycle 1 Days 1 and 11: pre-dose and at multiple time points (up to 72 hours) post-dose

,,,,
Interventionnanogram*hour per milliliter (ng*hr/mL) (Geometric Mean)
Cycle 1 Day 1Cycle 1 Day 11
Part 1: Ixazomib 0.5 mg/m^291.6301.00
Part 1: Ixazomib 1 mg/m^2191.87579.91
Part 1: Ixazomib 1.33 mg/m^2391.461161.92
Part 1: Ixazomib 1.76 mg/m^2522.741542.64
Part 1: Ixazomib 2.34 mg/m^2620.03800.0

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Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs)

(NCT00830869)
Timeframe: Part 1: Cycle 1 Day 1 up to Cycle 10 Day 41; Part 2: Cycle 1 Day 1 up to Cycle 12 Day 41

,,,,,,,,,,,
Interventionparticipants (Number)
TEAEsSAEs
Part 1: Ixazomib 0.125 mg/m^211
Part 1: Ixazomib 0.25 mg/m^211
Part 1: Ixazomib 0.5 mg/m^210
Part 1: Ixazomib 1 mg/m^271
Part 1: Ixazomib 1.33 mg/m^241
Part 1: Ixazomib 1.76 mg/m^264
Part 1: Ixazomib 2.34 mg/m^233
Part 2: Ixazomib 1.76 mg/m^2-Head and Neck Cancer (H&N)2210
Part 2: Ixazomib 1.76 mg/m^2-Prostate Cancer (PC)116
Part 2: Ixazomib 1.76 mg/m^2-Soft Tissue Sarcoma (STC)197
Part 2: Ixazomib 1.76 mg/m^2-TPEC2011
Part 2:Ixazomib 1.76 mg/m^2-Non-small Cell Lung Cancer(NSCLC)209

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Part 2: Ixazomib Concentration in Postdose Clinical Tumor Samples in Ixazomib 1.76 mg/m^2-TPEC

The average data of Days 1 and 4 of Cycle 1 was reported. (NCT00830869)
Timeframe: Cycle 1 Days 1 and 4: Predose and (from 4-20 hours) post-dose

Interventionnanogram per gram (ng/g) (Mean)
Part 2: Ixazomib 1.76 mg/m^2-TPEC525

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Part 1: Terminal Phase Elimination Half-life (T1/2) for Ixazomib

T1/2 is the time required for half of the drug to be eliminated from the plasma. (NCT00830869)
Timeframe: Part 1: Cycle 1 Day 11 pre-dose and at multiple time points (up to 264 hours) post-dose

Interventionhours (Geometric Mean)
Part 1: Ixazomib 1 mg/m^2171.90
Part 1: Ixazomib 1.33 mg/m^2144.69
Part 1: Ixazomib 1.76 mg/m^2104.84
Part 1: Ixazomib 2.34 mg/m^290.80

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Part 1: Rac: Accumulation Ratio for Ixazomib

Rac was estimated as the ratio of AUC (0-72) on Day 11 and AUC (0-72) on Day 1. AUC (0-72) is the area under the plasma concentration-time curve from time 0 to 72 hours post-dose. (NCT00830869)
Timeframe: Cycle 1 Day 11 pre-dose and at multiple time points (up to 72 hours) post-dose

Interventionratio (Geometric Mean)
Part 1: Ixazomib 0.125 mg/m^22.210
Part 1: Ixazomib 0.25 mg/m^25.160
Part 1: Ixazomib 0.5 mg/m^23.290
Part 1: Ixazomib 1 mg/m^22.996
Part 1: Ixazomib 1.33 mg/m^22.831
Part 1: Ixazomib 1.76 mg/m^23.086
Part 1: Ixazomib 2.34 mg/m^26.130

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Part 1: Number of Participants With Dose Limiting Toxicity (DLT)

Toxicity according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 3.0. DLT is any of following related to ixazomib:Grade (GR) 4 neutropenia (absolute neutrophil count<500 cells/cubic meter[cells/mm^3])for>7 days; GR 3 neutropenia with coincident fever and/or infection; GR 4 thrombocytopenia (platelets <25,000 cells/mm3)for>7 days; GR 3 thrombocytopenia with clinically significant bleeding; Platelet count<10,000 cells/mm3; GR 3 peripheral neuropathy;>=GR 3 nausea/emesis in absence of optimal antiemetic therapy; >=GR 3 diarrhoea in absence of optimal supportive therapy;GR 3 QTc prolongation noted on average of 3 electrocardiograms (ECGs);>=GR 3 nonhematological toxicity except GR 3 arthralgia/myalgia or GR 3 fatigue for<1 week; Delay in initiation of subsequent therapy cycle by>7 days due to treatment-related toxicity Other>=GR 2 nonhematological toxicity that opinion of investigator, requires discontinuation of therapy with Ixazomib. (NCT00830869)
Timeframe: Part 1: Cycle 1 Day 1 up to Cycle 1 Day 21

Interventionparticipants (Number)
Part 1: Ixazomib 0.125 mg/m^20
Part 1: Ixazomib 0.25 mg/m^20
Part 1: Ixazomib 0.5 mg/m^20
Part 1: Ixazomib 1 mg/m^21
Part 1: Ixazomib 1.33 mg/m^20
Part 1: Ixazomib 1.76 mg/m^21
Part 1: Ixazomib 2.34 mg/m^23

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Number of Participants With Clinically Significant Change From Baseline in Vital Signs

Vital sign measurements included diastolic and systolic blood pressure, heart rate, weight and oral temperature. (NCT00830869)
Timeframe: Day 1 up to 30 days after last dose of study drug (Cycle 12 Day 41)

Interventionparticipants (Number)
Part 1: Ixazomib 0.125 mg/m^20
Part 1: Ixazomib 0.25 mg/m^20
Part 1: Ixazomib 0.5 mg/m^20
Part 1: Ixazomib 1 mg/m^20
Part 1: Ixazomib 1.33 mg/m^20
Part 1: Ixazomib 1.76 mg/m^20
Part 1: Ixazomib 2.34 mg/m^20
Part 2:Ixazomib 1.76 mg/m^2-Non-small Cell Lung Cancer(NSCLC)0
Part 2: Ixazomib 1.76 mg/m^2-Head and Neck Cancer (H&N)0
Part 2: Ixazomib 1.76 mg/m^2-Soft Tissue Sarcoma (STC)0
Part 2: Ixazomib 1.76 mg/m^2-Prostate Cancer (PC)0
Part 2: Ixazomib 1.76 mg/m^2-TPEC0

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Part 1: TEmax: Time to Maximum Observed Effect (Emax) for Ixazomib

TEmax is the time to reach the Emax, equal to time (hours) to Emax. (NCT00830869)
Timeframe: Part 1: Cycle 1 Days 1 and 11 pre-dose and at multiple time points (up to 72 hours) post-dose; Cycle 1 Day 11 pre-dose and at multiple time points (up to 264 hours) post-dose

,,,,,,
Interventionhour (Median)
Cycle 1 Day 1Cycle 1 Day 11
Part 1: Ixazomib 0.125 mg/m^21.00024.000
Part 1: Ixazomib 0.25 mg/m^20.1000.080
Part 1: Ixazomib 0.5 mg/m^20.2500.100
Part 1: Ixazomib 1 mg/m^20.1000.110
Part 1: Ixazomib 1.33 mg/m^20.2500.080
Part 1: Ixazomib 1.76 mg/m^20.0800.120
Part 1: Ixazomib 2.34 mg/m^20.0800.100

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Part 1: E Max: Maximum Observed Effect for Ixazomib

E max is the maximum inhibition of 20S proteasome activity in whole blood. (NCT00830869)
Timeframe: Part 1: Cycle 1 Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose; Cycle 1 Day 11 pre-dose and at multiple time points (up to 264 hours) post-dose

,,,,,,
Interventionpercentage of inhibition (Mean)
Cycle 1 Day 1Cycle 1 Day 11
Part 1: Ixazomib 0.125 mg/m^27.704.50
Part 1: Ixazomib 0.25 mg/m^217.9010.00
Part 1: Ixazomib 0.5 mg/m^228.2046.10
Part 1: Ixazomib 1 mg/m^235.2239.33
Part 1: Ixazomib 1.33 mg/m^246.7354.30
Part 1: Ixazomib 1.76 mg/m^262.2061.90
Part 1: Ixazomib 2.34 mg/m^267.4070.40

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Part 1: C0: Initial Plasma Concentration After Bolus Intravenous Administration

C0 is the plasma drug concentration at time zero following bolus intravenous injection. (NCT00830869)
Timeframe: Part 1: Cycle 1 Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose; Cycle 1 Day 11 pre-dose and at multiple time points (up to 264 hours) post-dose

,,,,,,
Interventionnanogram per mililiter (ng/mL) (Geometric Mean)
Cycle 1 Day 1Cycle 1 Day 11
Part 1: Ixazomib 0.125 mg/m^215.127.1
Part 1: Ixazomib 0.25 mg/m^282.569.0
Part 1: Ixazomib 0.5 mg/m^2192.083.8
Part 1: Ixazomib 1 mg/m^2346.70272.57
Part 1: Ixazomib 1.33 mg/m^2366.16390.08
Part 1: Ixazomib 1.76 mg/m^2579.54648.97
Part 1: Ixazomib 2.34 mg/m^2901.0869.0

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Part 1: AUC (0-72): Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours Post-dose for Ixazomib

AUC (0-72) is a measure of the area under the plasma concentration-time curve from time 0 to 72 hours post-dose for ixazomib. (NCT00830869)
Timeframe: Part 1: Cycle 1 Days 1 and 11: pre-dose and at multiple time points (up to 72 hours) post-dose

Interventionnanogram*hour per milliliter (ng*hr/mL) (Geometric Mean)
Cycle 1 Day 11
Part 1: Ixazomib 0.25 mg/m^260.9

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Number of Participants With Best Overall Response

Best overall response for a participant is best observed post-baseline disease response as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 criteria. Complete Response (CR): disappearance of all target lesions, non-target lesions and normalization of tumor marker level. Partial Response (PR): at least 30% decrease in sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the baseline smallest sum of longest diameter; persistence of 1 or more non-target lesion(s) or maintenance of tumor marker level above normal limits. Progressive disease: at least 20% increase in the sum of the longest diameter of target lesions, taking as reference the baseline smallest sum of longest diameter or appearance of 1 or more new lesions or unequivocal progression of existing non-target lesions. (NCT00830869)
Timeframe: Day 18 up to Day 21 of each cycle (Part 1: up to Cycle 10; Part 2: up to Cycle 12)

,,,,,,,,,,,
Interventionparticipants (Number)
CRPRSDProgressive disease
Part 1: Ixazomib 0.125 mg/m^20001
Part 1: Ixazomib 0.25 mg/m^20010
Part 1: Ixazomib 0.5 mg/m^20001
Part 1: Ixazomib 1 mg/m^20015
Part 1: Ixazomib 1.33 mg/m^20003
Part 1: Ixazomib 1.76 mg/m^20023
Part 1: Ixazomib 2.34 mg/m^20020
Part 2: Ixazomib 1.76 mg/m^2-Head and Neck Cancer (H&N)0158
Part 2: Ixazomib 1.76 mg/m^2-Prostate Cancer (PC)0037
Part 2: Ixazomib 1.76 mg/m^2-Soft Tissue Sarcoma (STC)0088
Part 2: Ixazomib 1.76 mg/m^2-TPEC00314
Part 2:Ixazomib 1.76 mg/m^2-Non-small Cell Lung Cancer(NSCLC)00510

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Number of Participants With Clinically Significant Change From Baseline in Vital Signs

Vital signs included body temperature, weight, systolic and diastolic blood pressure and heart rate. (NCT00893464)
Timeframe: Baseline and Days 1, 8, 15 of each treatment cycle up to 45 treatment cycles

Interventionparticipants (Number)
Ixazomib 0.125 mg/m^20
Ixazomib 0.25 mg/m^20
Ixazomib 0.5 mg/m^20
Ixazomib 1.0 mg/m^20
Ixazomib 1.4 mg/m^20
Ixazomib1.76 mg/m^20
Ixazomib 2.34 mg/m^20
Ixazomib 3.11 mg/m^20

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Maximum Tolerated Dose (MTD)

The MTD was defined as the highest dose of ixazomib that generated dose limiting toxicity (DLT) during Cycle 1 in 0 of 3 or 1 of 6 participants. DLT defined as any of the following considered possibly related to therapy by investigator: Grade 4 neutropenia (absolute neutrophil count [ANC] <500 cell per cubic millimeter [cells/mm^3]) for >7 days; Grade 3 neutropenia with fever or infection; Grade 4 thrombocytopenia for >7 days; platelet count <25,000 cells/mm^3; Grade 3 thrombocytopenia with clinically significant bleeding; platelet count <10,000/mm^3; Grade 2 peripheral neuropathy with pain or Grade 3 peripheral neuropathy; >=Grade 3 nausea/emesis, diarrhea controlled by maximal supportive therapy; Grade 3 QTc prolongation>500 millisecond (msec);any >=Grade 3 nonhematologic toxicity except arthralgia/myalgia; <1 week fatigue; delay in the initiation of the subsequent therapy cycle by >=7 days ; other Grade 2 ixazomib-related nonhematologic toxicities requiring therapy discontinuation. (NCT00893464)
Timeframe: Treatment Cycle 1

Interventionmg/m^2 (Number)
All Participants2.34

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Terminal Phase Elimination Half-life (T1/2) for Ixazomib

Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma. (NCT00893464)
Timeframe: Cycle 1 Day 15: Predose and at multiple time points (up to 336 hours postdose)

Interventionhr (Geometric Mean)
Ixazomib 0.5 mg/m^2292.00
Ixazomib 1.0 mg/m^2146.00
Ixazomib 1.4 mg/m^2209.39
Ixazomib1.76 mg/m^2145.57
Ixazomib 2.34 mg/m^2107.58
Ixazomib 3.11 mg/m^2108.39

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CLr: Renal Clearance

CLr is the volume of plasma from which the drug is completely removed by the kidney in a given amount of time, calculated as the amount of drug excreted in the urine divided by the area under the plasma concentration-time curve, expressed in liter per hour (L/hr). (NCT00893464)
Timeframe: Cycle 1, Days 1 and 15: 0 to 4 hours postdose

,,,,,
InterventionL/hr (Geometric Mean)
Day 1 (n= 0, 0,1, 0, 4, 6, 8, 5)Day 15 (n= 0, 0, 1, 1, 4, 3, 6, 2)
Ixazomib 0.5 mg/m^20.0000000.024200
Ixazomib 1.0 mg/m^2NA0.080500
Ixazomib 1.4 mg/m^20.0570580.098174
Ixazomib 2.34 mg/m^20.0448280.034181
Ixazomib 3.11 mg/m^20.0853030.085569
Ixazomib1.76 mg/m^20.1186860.098459

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AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for Ixazomib

AUC(0-168) is a measure of the area under the plasma concentration time-curve from time 0 to 168 hours postdose (NCT00893464)
Timeframe: Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose)

,,,,,
Interventionhour*nanogram per milliliter (hr*ng/mL) (Geometric Mean)
Day 1 (n= 0, 0, 0, 0, 4, 6, 7, 5)Day 15 (n= 0, 0, 1, 1, 4, 0, 7, 2)
Ixazomib 0.5 mg/m^2NA175.0
Ixazomib 1.0 mg/m^2NA732.0
Ixazomib 1.4 mg/m^2636.81385.4
Ixazomib 2.34 mg/m^21058.92108.7
Ixazomib 3.11 mg/m^21683.62537.2
Ixazomib1.76 mg/m^2821.0NA

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C0: Initial Plasma Concentration After Bolus Intravenous Administration

C0 is the plasma drug concentration at time zero following bolus intravenous injection, obtained from the plasma concentration-time curve. (NCT00893464)
Timeframe: Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 336 hours postdose)

,,,,,,,
Interventionnanogram per milliliter (ng/mL) (Geometric Mean)
Day 1 (n= 1, 1, 1, 0, 4, 7, 10, 5)Day 15 (n= 0, 0, 1, 1, 4, 3, 7, 2)
Ixazomib 0.125 mg/m^27.430NA
Ixazomib 0.25 mg/m^259.400NA
Ixazomib 0.5 mg/m^2106.00056.300
Ixazomib 1.0 mg/m^2NA383.000
Ixazomib 1.4 mg/m^2713.883497.189
Ixazomib 2.34 mg/m^2898.461802.825
Ixazomib 3.11 mg/m^2961.2051191.973
Ixazomib1.76 mg/m^2541.771499.027

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TEmax: Time to Maximum Observed Effect (Emax) for Ixazomib

TEmax: Time to reach the maximum observed effect (Emax), equal to time (hours) to Emax. (NCT00893464)
Timeframe: Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose)

,,,,,,,
Interventionhr (Median)
Day 1 (n= 1, 1, 1, 1, 3, 7, 5, 4)Day 15 (n= 0, 1, 1, 1, 3, 3, 4, 2)
Ixazomib 0.125 mg/m^20.25000NA
Ixazomib 0.25 mg/m^20.083300.10000
Ixazomib 0.5 mg/m^20.100000.10000
Ixazomib 1.0 mg/m^20.083300.08330
Ixazomib 1.4 mg/m^20.117000.08330
Ixazomib 1.76 mg/m^20.083300.08330
Ixazomib 2.34 mg/m^20.083300.16665
Ixazomib 3.11 mg/m^20.108500.10015

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Ae (0-4): Amount of Drug Excreted in Urine From 0 to 4 Hours Postdose

Ae (0-4) is the total amount of drug excreted in the urine from 0 to 4 hours postdose. (NCT00893464)
Timeframe: Cycle 1, Days 1 and 15: 0 to 4 hours postdose

,,,,,,,
Interventionnanogram (Geometric Mean)
Day 1 (n= 1, 1, 1, 0, 4, 6, 8, 5)Day 15 (n= 0, 1, 1, 1, 4, 3, 7, 2)
Ixazomib 0.125 mg/m^20NA
Ixazomib 0.25 mg/m^21440661.0
Ixazomib 0.5 mg/m^20568.0
Ixazomib 1.0 mg/m^2NA10200
Ixazomib 1.4 mg/m^28584.416711.7
Ixazomib 2.34 mg/m^29897.813128.2
Ixazomib 3.11 mg/m^225710.440712.9
Ixazomib1.76 mg/m^217963.717982.2

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Overall Best Response

Overall best response is the best response observed for a participant during the study based on International Working Group (IWG) Response Criteria for malignant lymphoma. Complete response (CR) as per IWG is complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. Partial response (PR) is a minimum of 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses and no increase in the size of other nodes. Stable disease (SD) is when a participant fails to attain the criteria needed for a CR or PR, but does not fulfill those for PD. PD is any new lesion or increase by >50% of previously involved sites from nadir. (NCT00893464)
Timeframe: Baseline up to Cycle 45

,,,,,,,
Interventionparticipants (Number)
CRPRSDPD
Ixazomib 0.125 mg/m^20001
Ixazomib 0.25 mg/m^20001
Ixazomib 0.5 mg/m^20010
Ixazomib 1.0 mg/m^20001
Ixazomib 1.4 mg/m^20112
Ixazomib 1.76 mg/m^21024
Ixazomib 2.34 mg/m^20224
Ixazomib 3.11 mg/m^20102

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Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event. (NCT00893464)
Timeframe: Baseline up to 30 days after last dose of study drug

,,,,,,,
Interventionparticipants (Number)
Adverse EventsSerious Adverse Events
Ixazomib 0.125 mg/m^210
Ixazomib 0.25 mg/m^210
Ixazomib 0.5 mg/m^210
Ixazomib 1.0 mg/m^210
Ixazomib 1.4 mg/m^242
Ixazomib 2.34 mg/m^2104
Ixazomib 3.11 mg/m²53
Ixazomib1.76 mg/m^271

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Rac: Accumulation Ratio for Ixazomib

Rac was estimated as the ratio of AUC (0-168) on Day 15 and AUC (0-168) on Day 1. AUC (0-168) is the area under the plasma concentration-time curve from time 0 to 168 hours postdose. (NCT00893464)
Timeframe: Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose)

Interventionratio (Geometric Mean)
Ixazomib 1.4 mg/m^22.174
Ixazomib 2.34 mg/m^22.267
Ixazomib 3.11 mg/m^22.113

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Fe (0-4): Fraction of Dose Excreted Unchanged in Urine From 0 to 4 Hours Postdose

Fe (0-4) is the fraction of the dose excreted unchanged in the urine from 0 to 4 hours postdose, calculated as percentage of the exact dose administered. (NCT00893464)
Timeframe: Cycle 1, Days 1 and 15: 0 to 4 hours postdose

,,,,,,,
Interventionpercentage of dose (Geometric Mean)
Day 1 (n= 1, 1, 1, 0, 4, 6, 8, 5)Day 15 (n= 0, 1, 1, 1, 4, 3, 7, 2)
Ixazomib 0.125 mg/m^20NA
Ixazomib 0.25 mg/m^20.307000.14100
Ixazomib 0.5 mg/m^200.04900
Ixazomib 1.0 mg/m^2NA0.53600
Ixazomib 1.4 mg/m^20.298420.58105
Ixazomib 2.34 mg/m^20.236830.31852
Ixazomib 3.11 mg/m^20.423940.65344
Ixazomib1.76 mg/m^20.568960.55331

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Emax: Maximum Observed Effect for Ixazomib

Emax is the maximum inhibition of 20S proteasome activity in whole blood. (NCT00893464)
Timeframe: Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose)

,,,,,,,
Interventionpercentage of inhibition (Mean)
Day 1 (n= 1, 1, 1, 1, 3, 7, 5, 4)Day 15 (n= 0, 1, 1, 1, 3, 3, 4, 2)
Ixazomib 0.125 mg/m^25.150NA
Ixazomib 0.25 mg/m^218.50064.300
Ixazomib 0.5 mg/m^233.20019.200
Ixazomib 1.0 mg/m^250.50044.400
Ixazomib 1.4 mg/m^266.33369.800
Ixazomib 1.76 mg/m^272.18674.833
Ixazomib 2.34 mg/m^281.86079.625
Ixazomib 3.11 mg/m^280.20083.650

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AUC(0-last): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ixazomib

(NCT00932698)
Timeframe: Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 264 hours) postdose

,,,,,,,,,,
Interventionhr*ng/mL (Mean)
Day 1Day 11
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2509.0001010.000
Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^23.38356.533
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^220.700177.667
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2109.000458.000
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2159.050605.000
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2251.000808.500
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2449.0001435.600
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2416.5001915.000
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2410.0002297.200
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2418.175903.846
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2351.000937.857

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Cmax: Maximum Observed Plasma Concentration for Ixazomib

(NCT00932698)
Timeframe: Cycle 1, Days 1 and 11: Predose and at multiple time points (up to 264 hours) postdose

,,,,,,,,,,
Interventionng/mL (Mean)
Day 1Day 11
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^226.60027.200
Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^22.1202.837
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^210.1908.857
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^222.20031.650
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^229.00056.500
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^221.100101.100
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^268.16785.420
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2117.933105.450
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^285.600109.660
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^258.90059.871
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^259.34361.800

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Number of Participants With Clinically Significant Changes in Vital Signs Reported as TEAEs

The number of participants with any clinically significant changes in vital signs collected throughout the study that were reported as TEAEs. Measurement of vital signs, included oral temperature, blood pressure, and heart rate. (NCT00932698)
Timeframe: From first dose of the study drug through 30 days after the last dose of study drug or start of subsequent antineoplastic therapy (Up to 81.1 months)

InterventionParticipants (Count of Participants)
Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^20
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^20
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^20
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^20
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^20
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^20
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^21
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^20
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^20
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^20
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^20

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Number of Participants With Clinically Significant Abnormalities Reported as TEAEs

The number of participants with any clinically significant abnormal standard safety laboratory values collected throughout the study reported as TEAEs. Parameters assessed were hematology, serum chemistry and urinalysis. (NCT00932698)
Timeframe: From first dose of the study drug through 30 days after the last dose of study drug or start of subsequent antineoplastic therapy (Up to 81.1 months)

,,,,,,,,,,
InterventionParticipants (Count of Participants)
Blood Creatinine IncreasedBlood Urea IncreasedWhite Blood Cell Count DecreasedNeutrophil Count DecreasedAlanine Aminotransferase IncreasedLiver Function Test IncreasedBlood Calcium IncreasedPlatelet Count DecreasedHaematocrit DecreasedHaemoglobin Decreased
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^20000000000
Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^21000000000
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^21000000000
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^21000001000
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^20000000000
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^20010000000
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^21000000000
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^21011000100
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^20100000000
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^22000110000
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^22101000011

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Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib

(NCT00932698)
Timeframe: Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 264 hours) postdose

,,,,,,,,,,
Interventionhours (Median)
Day 1Day 11
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^21.0001.500
Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^21.0001.100
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^21.0001.000
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^20.7751.275
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^20.7750.500
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^21.0001.000
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^21.0000.667
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^21.0000.832
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^20.5251.500
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^21.0001.010
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^20.6170.583

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Number of Participants With One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

An AE is any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. An SAE is any untoward medical occurrence that results in death;is life-threatening;requires inpatient hospitalization or prolongation of present hospitalization;results in persistent or significant disability/incapacity;is a congenital anomaly/birth defect;or is a medically important event that may not be immediately life-threatening or result in death or hospitalization, but may jeopardize the participant or may require intervention to prevent one of other outcomes listed in definition above, or involves suspected transmission via a medicinal product of an infectious agent. A TEAE is defined as an AE that occurs after administration of first dose of study drug and through 30 days after last dose of study drug or until start of subsequent antineoplastic therapy. (NCT00932698)
Timeframe: From first dose of the study drug through 30 days after the last dose of study drug or start of subsequent antineoplastic therapy (Up to 81.1 months)

,,,,,,,,,,
InterventionParticipants (Count of Participants)
AEsSAEs
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^222
Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^230
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^230
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^232
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^232
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^230
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^275
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^243
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^263
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^22014
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2126

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Overall Response Rate (ORR)

ORR is defined as percentage of participants with complete response (CR) or partial response (PR) or minimal response (MR) as assessed by the investigator using International Myeloma Working Group Uniform Response criteria. CR=Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow. PR=≥50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥90% or to <200 mg /24 h. MR=25-49% reduction in the serum monoclonal paraprotein maintained for a minimum of 6 weeks; 50-89% reduction in 24-h urinary light chain excretion, which still exceeds 200 mg/24 h, maintained for a minimum of 6 weeks; for participants with non-secretory myeloma only, 25-49% reduction in plasma cells in a bone marrow aspirate and on trephine biopsy, if biopsy is performed, maintained for a minimum of 6 weeks; 25-49% reduction in the size of soft tissue plasmacytomas; no increase in the size or number of lytic bone lesions. (NCT00932698)
Timeframe: Cycle 1 through Cycle 115 (Up to 80.1 months)

,,,,,,,,,,
Interventionpercentage of participants (Number)
CR+PRCR+PR+MR
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^200
Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^200
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^200
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^200
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^23333
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^200
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^200
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^25050
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^23333
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2510
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2918

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Number of Participants With a TEAE of Peripheral Neuropathy

Neurotoxicity was assessed as the number of participants with the TEAE of peripheral neuropathy. (NCT00932698)
Timeframe: From first dose of the study drug through 30 days after the last dose of study drug or start of subsequent antineoplastic therapy (Up to 81.1 months)

,,,,,,,,,,
InterventionParticipants (Count of Participants)
Neuropathy PeripheralPeripheral Sensory Neuropathy
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^200
Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^200
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^210
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^210
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^200
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^201
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^210
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^200
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^210
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^230
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^230

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T1/2: Terminal Disposition Phase Elimination Half-life for Ixazomib

(NCT00932698)
Timeframe: Cycle 1, Day 11: predose and at multiple time points (up to 264 hours) postdose

Interventionhr (Mean)
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2135.00
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2126.50
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2129.33
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2105.88
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^292.70
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2115.85
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2123.06
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2124.93
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2134.00

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λz: Terminal Disposition Phase Rate Constant for Ixazomib

(NCT00932698)
Timeframe: Cycle 1, Day 11: predose and at multiple time points (Up to 264 hours) postdose

Intervention1/hr (Mean)
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^20.005
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^20.005
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^20.006
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^20.007
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^20.008
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^20.006
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^20.006
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^20.006
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^20.005

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Maximum Tolerated Dose (MTD) of Ixazomib

MTD was highest dose of Ixazomib, at which <=1 of 6 participants experienced dose-limiting toxicity (DLT) during Cycle 1 of Phase 1. DLT was defined as any of following considered possibly related to therapy: Grade 4 neutropenia (absolute neutrophil count [ANC] <500 cell per cubic millimeter [cells/mm^3]) for >7 days;Grade 3 neutropenia with fever or infection; Grade 4 thrombocytopenia (platelets < 25,000/mm^3) for >7 days;Grade 3 thrombocytopenia with clinically significant bleeding; platelet count <10,000/mm^3; Grade 2 peripheral neuropathy with pain or >=Grade 3 peripheral neuropathy; >=Grade 3 nausea/emesis, diarrhea controlled by supportive therapy; Grade 3 QTc prolongation (QTc >500 millisecond [msec]);any >=Grade 3 nonhematologic toxicity except Grade 3 arthralgia/myalgia; or <1 week Grade 3 fatigue; delay in initiation of the subsequent therapy cycle by >2 weeks; other >=Grade 2 study drug-related nonhematologic toxicities requiring therapy discontinuation. (NCT00932698)
Timeframe: Cycle 1 (21 days)

Interventionmg/m^2 (Number)
Ixazomib (All Groups)2

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AUC(0-72): Area Under the Plasma Concentration-Time Curve From Time 0 to 72 Hours Postdose for Ixazomib

(NCT00932698)
Timeframe: Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 72 hours) postdose

,
Interventionhr*ng/mL (Mean)
Day 11
Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^256.53
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2177.67

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AUC(0-72): Area Under the Plasma Concentration-Time Curve From Time 0 to 72 Hours Postdose for Ixazomib

(NCT00932698)
Timeframe: Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 72 hours) postdose

,,,,,,,,
Interventionhr*ng/mL (Mean)
Day 1Day 11
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2509.001010.00
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2109.00458.00
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2159.05605.00
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2251.00808.50
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2449.001435.60
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2416.501915.00
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2410.002297.20
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2451.64903.85
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2351.00937.86

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Accumulation Ratio: Day 15 AUC0-168 / Day 1 AUC0-168 for MLN2238

MLN2238 is the complete hydrolysis product of the study drug ixazomib citrate (MLN9708). (NCT00963820)
Timeframe: Day 15 of Cycle 1

Interventionunitless (Mean)
1.68 mg/m^22.64
2.23 mg/m^21.45
2.97 mg/m^22.25
3.95 mg/m^21.19
Relapsed and Refractory (RR)2.25
VELCADE-relapsed (VR)2.19
PI naïve1.97
Carfilzomib2.37

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Overall Response to Treatment With Ixazomib Citrate Based on Investigator's Evaluation Over Time

"Responses were based on International Myeloma Working Group Uniform Criteria. Complete Response (CR)=Negative immunofixation on serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow.~Partial Response (PR)= reduction in M-Protein ≥50% in serum and ≥90% in 24-hour urine. If M-protein unmeasurable, ≥50% decrease in difference of involved and uninvolved Free Light Chain (FLC). If M-protein and FLC unmeasurable, ≥50% reduction in plasma cells is required, if baseline bone marrow plasma cell ≥30%. And ≥50% reduction in the size of soft tissue plasmacytomas.~Minimal Response (MR)= 25-49% reduction in serum paraprotein for 6 weeks. 50-89% reduction in 24 hour urinary light chain excretion for 6 weeks. For Non-secretory myeloma patients, 25-49 % reduction in plasma cells in bone marrow and trephine biopsy for a 6 weeks. 25-49% reduction in the size of soft tissue plasmacytomas. No increase in the size or number of lytic bone lesions." (NCT00963820)
Timeframe: Up to 354 days

,,,,,,,,,,,
Interventionpercentage of participants (Number)
CR + PRCR + PR + MR
0.24 mg/m^200
0.48 mg/m^200
0.80 mg/m^200
1.20 mg/m^200
1.68 mg/m^200
2.23 mg/m^200
2.97 mg/m^22525
3.95 mg/m^22525
Carfilzomib2525
PI naïve1717
Relapsed and Refractory (RR)918
VELCADE-relapsed (VR)2233

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Number of Participants Reporting One or More Treatment-Emergent Adverse Events and Serious Adverse Events

"An Adverse Event is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.~A Serious Adverse Event (SAE) was any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant." (NCT00963820)
Timeframe: From the first dose through 30 days after last dose of ixazomib citrate or until the start of subsequent antineoplastic therapy (Up to 354 days)

Interventionparticipants (Number)
0.24 mg/m^23
0.48 mg/m^23
0.80 mg/m^22
1.20 mg/m^23
1.68 mg/m^24
2.23 mg/m^23
2.97 mg/m^28
3.95 mg/m^25
Relapsed and Refractory (RR)11
VELCADE-relapsed (VR)10
PI naïve6
Carfilzomib4

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Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for MLN2238

Tmax: Time to reach the maximum observed plasma concentration (Cmax), equal to time to Cmax. MLN2238 is the complete hydrolysis product of the study drug ixazomib citrate (MLN9708). (NCT00963820)
Timeframe: Days 1 and 15 of Cycle 1

,,,,,,,,,,,
Interventionhours (Median)
Cycle 1 Day 1 (n=1,1,2,1,3,2,5,4,5,8,5,3)Cycle 1 Day 15 (n=3,1,3,2,2,1,2,1,5,5,4,3)
0.24 mg/m^21.501.07
0.48 mg/m^21.530.50
0.80 mg/m^21.521.83
1.20 mg/m^21.001.00
1.68 mg/m^21.521.27
2.23 mg/m^21.258.00
2.97 mg/m^21.001.25
3.95 mg/m^21.001.03
Carfilzomib1.421.03
PI naïve1.001.00
Relapsed and Refractory (RR)2.001.50
VELCADE-relapsed (VR)0.501.00

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Neurotoxicity Grading

Neurotoxicity is graded using participant responses to 11 functional questions on a 5-point scale, where 0=Not at all and 4=Very much, using the Functional Assessment of Cancer Therapy/Gynecology Oncology Group - Neurotoxicity Questionnaire, Version 4.0(14). Neurotoxicity subscale is a sum of 11 reversed item scores where each original score is transformed as (4 - score). The highest possible score is 44, and a higher score indicates more neurotoxicity. (NCT00963820)
Timeframe: Cycle 1 Day 1 and End of Study (Up to 354 days)

,,,,,,,,,,,
Interventionscore on a scale (Mean)
Cycle 1 Day 1 (n=2,3,3,3,4,3,7,4,9,8,6,4)End of Study (n=3,3,2,1,1,3,4,3,8,5,4,3)
0.24 mg/m^236.0025.00
0.48 mg/m^240.3340.67
0.80 mg/m^242.0038.50
1.20 mg/m^236.0035.00
1.68 mg/m^239.5042.00
2.23 mg/m^236.8036.00
2.97 mg/m^233.1436.00
3.95 mg/m^238.5033.33
Carfilzomib32.0027.33
PI naïve38.0037.00
Relapsed and Refractory (RR)38.4433.88
VELCADE-relapsed (VR)33.7327.24

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Cmax: Maximum Observed Plasma Concentration for MLN2238

Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. MLN2238 is the complete hydrolysis product of the study drug ixazomib citrate (MLN9708). (NCT00963820)
Timeframe: Days 1 and 15 of Cycle 1

,,,,,,,,,,,
Interventionng/mL (Mean)
Cycle 1 Day 1 (n=1,1,2,1,3,2,5,4,5,8,5,3)Cycle 1 Day 15 (n=3,1,3,2,2,1,2,1,5,5,4,3)
0.24 mg/m^23.0103.64
0.48 mg/m^22.914.64
0.80 mg/m^25.756.89
1.20 mg/m^215.1017.90
1.68 mg/m^213.8317.63
2.23 mg/m^229.059.24
2.97 mg/m^265.46100.55
3.95 mg/m^2123.95134.00
Carfilzomib83.7355.10
PI naïve77.70118.05
Relapsed and Refractory (RR)75.9250.46
VELCADE-relapsed (VR)110.4393.68

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AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for MLN2238

AUC(0-168) is a measure of the area under the plasma concentration-time curve over the dosing interval (tau) (AUC[0-tau]), where tau is the length of the dosing interval - 168 hours in this study). MLN2238 is the complete hydrolysis product of the study drug ixazomib citrate (MLN9708). (NCT00963820)
Timeframe: Days 1 and 15 of Cycle 1

,,,,,,,,,,,
Interventionhr*ng/mL (Mean)
Cycle 1 Day 1 (n=0,0,0,0,2,1,3,4,3,5,4,3)Cycle 1 Day 15 (n=0,0,2,0,2,1,2,1,1,4,3,2)
0.24 mg/m^2NANA
0.48 mg/m^2NANA
0.80 mg/m^2NA398.50
1.20 mg/m^2NANA
1.68 mg/m^2258.00663.00
2.23 mg/m^2598.00868.00
2.97 mg/m^21269.673100.00
3.95 mg/m^21371.251460.00
Carfilzomib813.672075.00
PI naïve750.251549.00
Relapsed and Refractory (RR)1793.333690.00
VELCADE-relapsed (VR)854.201777.75

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Terminal Phase Elimination Half-life (T1/2) for MLN2238

Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma. MLN2238 is the complete hydrolysis product of the study drug ixazomib citrate (MLN9708). (NCT00963820)
Timeframe: Day 15 of Cycle 1

Interventionhour (Mean)
0.80 mg/m^2271.00
1.20 mg/m^2190.50
1.68 mg/m^2189.00
2.23 mg/m^2175.00
2.97 mg/m^2246.00
3.95 mg/m^2165.00
Relapsed and Refractory (RR)186.00
VELCADE-relapsed (VR)202.33
PI naïve123.90
Carfilzomib108.00

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Terminal Elimination Rate Constant (λz) for MLN2238

Terminal elimination rate constant (λz) is the rate at which drugs are eliminated from the body and the values were used for calculation of T1/2. MLN2238 is the complete hydrolysis product of the study drug ixazomib citrate (MLN9708). (NCT00963820)
Timeframe: Day 15 of Cycle 1

Intervention1/hour (Mean)
0.80 mg/m^20.000
1.20 mg/m^20.000
1.68 mg/m^20.000
2.23 mg/m^20.00
2.97 mg/m^20.00
3.95 mg/m^20.00
Relapsed and Refractory (RR)0.00
VELCADE-relapsed (VR)0.00
PI naïve0.01
Carfilzomib0.01

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TEmax: Time of Occurrence of Emax

(NCT00963820)
Timeframe: Days 1 and 15 of Cycle 1

InterventionHours (Mean)
0.24 mg/m^2NA
0.48 mg/m^2NA
0.80 mg/m^2NA
1.20 mg/m^2NA
1.68 mg/m^2NA
2.23 mg/m^2NA
2.97 mg/m^2NA
3.95 mg/m^2NA
Relapsed and Refractory (RR)NA
VELCADE-relapsed (VR)NA
PI naïveNA
CarfilzomibNA

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Emax: Maximum Inhibition

A Whole Blood 20S Proteasome Inhibition Parameter. There were no subjects in the Pharmacodynamic (PD) Analysis Set for the 2.23 mg/m^2 cohort, so PD tables do not include that arm. (NCT00963820)
Timeframe: Days 1 and 15 of Cycle 1

InterventionPercentage of inhibition (Mean)
0.24 mg/m^2NA
0.48 mg/m^2NA
0.80 mg/m^2NA
1.20 mg/m^2NA
1.68 mg/m^2NA
2.23 mg/m^2NA
2.97 mg/m^2NA
3.95 mg/m^2NA
Relapsed and Refractory (RR)NA
VELCADE-relapsed (VR)NA
PI naïveNA
CarfilzomibNA

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Phase 2: 1 Year Survival Rate

1-year survival rate is defined as the percentage of participants still alive at year after the first dose of stud drug. (NCT01217957)
Timeframe: 1 year after first dose of study drug

Interventionpercentage of participants (Number)
Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone92
Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + Dexamethasone92

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Phase 2: Duration of Response (DOR)

DOR was measured as the time in months from the date of first documentation of a confirmed response (CR + PR+ VGPR) to the date of the first documented disease progression (PD). Response was assessed by the investigator using International Myeloma Working Group (IMWG) Criteria. CR=negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. VGPR=Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hours. (NCT01217957)
Timeframe: Up to 787 days

Interventionmonths (Median)
Phase 2: Ixazomib 4.0 mg + Lenalidomide + DexamethasoneNA
Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + DexamethasoneNA

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Phase 2: Objective Response Rate (ORR) Following Treatment With the Combination Of Oral Ixazomib, Lenalidomide And Low-Dose Dexamethasone

ORR was defined as the percentage of participants with Complete (CR) + Very Good Partial Response (VGPR) assessed by the investigatory using International Myeloma Working Group (IMWG) Criteria. CR=Negative immunofixation on the serum and urine and; disappearance of any soft tissue plasmacytomas and; < 5% plasma cells in bone marrow. VGPR=Serum and urine M-protein detectable by immunofixation but not on electrophoresis or; 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hours. (NCT01217957)
Timeframe: Until occurrence of progressive disease or unacceptable toxicity (Up to 787 days)

Interventionpercentage of participants (Number)
Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone59
Phase 2: Ixazomib 4.0mg/2.23 + Lenalidomide + Dexamethasone62

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Phase 2: Overall Response Rate (ORR)

ORR was defined as the percentage of participants with CR, VGPR and Partial Response (PR) assessed by the investigator using IMWG criteria. CR=Negative immunofixation on the serum and urine + Disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. PR=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 90% or to < 200 mg per 24 hours. VGPR= Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hours. (NCT01217957)
Timeframe: Up to 787 days

Interventionpercentage of participants (Number)
Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone88
Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + Dexamethasone88

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Phase 2: Overall Survival (OS)

OS was measured as the time in months from the first dose of study treatment to the date of death + 1 day. (NCT01217957)
Timeframe: From the first dose of study treatment to the date of death (up to 787 days)

Interventionparticipants (Median)
Phase 2: Ixazomib 4.0 mg + Lenalidomide + DexamethasoneNA
Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + DexamethasoneNA

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Phase 2: Progression Free Survival (PFS)

PFS was measured as the time in months from the first dose of study treatment to the date of the first documented PD or death. (NCT01217957)
Timeframe: Up to 787 days

Interventionmonths (Median)
Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone14.98
Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + DexamethasoneNA

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Phase 2: Time to Best Response

Time to Best Response was measured as the time in months from the first dose of study treatment to the date of first documented documentation of a confirmed response of partial response (PR) or better. (NCT01217957)
Timeframe: Up to 787 days

Interventionmonths (Median)
Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone2.96
Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + Dexamethasone3.01

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Phase 2: Time to Progression (TTP)

TTP was measured as the time in months from the first dose of study treatment to the date of the first documented progressive disease (PD). (NCT01217957)
Timeframe: From the first dose of study treatment to the date of first documented progressive disease (Up to 787 days)

Interventionmonths (Median)
Phase 2: Ixazomib 4.0 mg + Lenalidomide + DexamethasoneNA
Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + DexamethasoneNA

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Phase 1: AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for Ixazomib

AUC(0-168) is a measure of the area under the plasma concentration-time curve from time 0 to 168 hours postdose for Ixazomib. (NCT01217957)
Timeframe: Cycle 1, Days 1 and 15

,,,
Interventionhr*ng/mL (Geometric Mean)
Day 1 (n=1, 3, 4, 1)Day 15 (n=2, 3, 3, 1)
Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + DexamethasoneNA834.608
Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone587.6671083.998
Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone923.4841831.324
Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + DexamethasoneNANA

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Phase 1: Cmax: Maximum Observed Plasma Concentration for Ixazomib

Cmax: Maximum Observed Plasma Concentration (Cmax) is the peak plasma concentration of ixazomib obtained directly from the plasma concentration-time curve. (NCT01217957)
Timeframe: Cycle 1, Days 1 and 15

,,,
Interventionng/mL (Geometric Mean)
Day 1 (n=1, 3, 4, 1)Day 15 (n=2, 3, 4, 1)
Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + DexamethasoneNA11.999
Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone22.30331.368
Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone94.77953.517
Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + DexamethasoneNANA

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Phase 2: Percentage of Participants With Grade 3 or Higher AEs, SAEs and Treatment Discontinuation

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event. (NCT01217957)
Timeframe: Until occurrence of progressive disease or unacceptable toxicity (Up to 787 days)

,
Interventionpercentage of participants (Number)
Grade 3 or Higher AEsSAEsAEs Resulting in Treatment Discontinuation
Phase 2 :Ixazomib 4.0 mg + Lenalidomide + Dexamethasone76408
Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + Dexamethasone75438

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Phase 2: Percentage of Participants With Complete Response (CR), Stringent Complete Response (sCR), Very Good Partial Response (VGPR), Near Complete Response (nCR), Partial Response (PR) and Minimal Response (MR)

Response was assessed by the investigator using International Myeloma Working Group (IMWG) Criteria. CR=Negative immunofixation on the serum and urine + Disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. sCR= CR + Normal free light chain (FLC) ratio and Absence of clonal cells in bone marrow. PR=≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to < 200 mg per 24 hours. VGPR= Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hours. nCR=Positive immunofixation analysis of serum or urine as the only evidence of disease. Disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. MR=25% to 49% reduction in serum paraprotein and 50% to 89% reduction in urine light chain excretion for 6 weeks. (NCT01217957)
Timeframe: Cycles 3, 6, 9 and 12 (Up to 787 days)

,
Interventionpercentage of participants (Number)
CRsCRVGPRnCRPRMR
Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone206392676
Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + Dexamethasone2310382656

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Phase 2: Percentage of Participants With Complete Response (CR) and Very Good Partial Response (VGPR)

Response was assessed by the investigator using International Myeloma Working Group (IMWG) Criteria. CR is defined as negative immunofixation on the serum and urine and; disappearance of any soft tissue plasmacytomas and; < 5% plasma cells in bone marrow. VGPR is defined as Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hours. (NCT01217957)
Timeframe: After Cycles 3, 6 and 9 (Up to 787 days)

,
Interventionpercentage of participants (Number)
After 3 cyclesAfter 6 cyclesAfter 9 cycles
Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone354757
Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + Dexamethasone374858

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Phase 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event. (NCT01217957)
Timeframe: Until occurrence of progressive disease or unacceptable toxicity (Up to 336 days)

,,,
Interventionparticipants (Number)
Any AESAE
Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone32
Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone33
Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone61
Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone32

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Phase 1: Rac: Accumulation Ratio of Ixazomib

The accumulation ratio (Rac) was estimated as the ratio of AUC(0-168) on Day 15 to the AUC(0-168) on Day 1. AUC(0-168) is the area under the plasma concentration-time curve from time 0 to 168 hours postdose for ixazomib. (NCT01217957)
Timeframe: Cycle 1, Day 15

InterventionRatio (Geometric Mean)
Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + DexamethasoneNA
Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone1.849
Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone2.051

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Phase 1: Maximum Tolerated Dose (MTD) of Ixazomib Administered Weekly in Combination With Lenalidomide and Low-Dose Dexamethasone

MTD of ixazomib will be determined by assessing adverse events and serious adverse events, clinical laboratory values, neurotoxicity grading, and vital sign measurements. (NCT01217957)
Timeframe: Until occurrence of progressive disease or unacceptable toxicity (Up to 336 days)

Interventionmg/m^2 (Number)
Phase 1: Ixazomib + Lenalidomide + Dexamethasone2.97

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Phase 1: Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for Ixazomib

Tmax: Time to reach the first maximum observed plasma concentration (Cmax), equal to time (hours) to Cmax, obtained directly from the plasma concentration-time curve. (NCT01217957)
Timeframe: Cycle 1, Days 1 and 15

,,,
Interventionhours (Median)
Day 1 (n=1, 3, 4, 1)Day 15 (n=2, 3, 4, 1)
Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone1.0204.165
Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone1.5201.000
Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone1.0601.015
Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone0.2502.000

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Number of Participants With Best Hematologic Response to Treatment Based on Investigators Assessment

The overall hematologic response rate is defined as number of participants with complete response (CR) or partial response (PR) or very good partial response (VGPR) as assessed by the investigator. Response is determined according to standardized criteria using a central laboratory. CR=serum and urine negative for monoclonal protein by immunofixation; or free light chain ratio normal; < 5% plasma cells in bone marrow without clonal dominance. PR=reduction in dFLC > 50%. VGPR= dFLC < 40 mg/L. (NCT01318902)
Timeframe: Day 22 to 28 in each cycle and end of treatment visit; then every 6 weeks thereafter until disease progression or initiation of subsequent antineoplastic therapy (Up to approximately 12 months)

InterventionParticipants (Count of Participants)
Dose Escalation Cohort: Ixazomib 4.0 mg4
Dose Escalation Cohort: Ixazomib 5.5 mg0
Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)4
Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)3

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Cmax: Maximum Observed Plasma Concentration for Ixazomib

(NCT01318902)
Timeframe: Cycle 1: Day 1 (MTD cohort participants only, 4.0 mg) and Day 15 (all participants enrolled in the study): predose (within 1 hour (hr) before dosing), and postdose at multiple timepoints up to 168 hr

Interventionng/mL (Mean)
Cycle 1, Day 1Cycle 1, Day 15
Ixazomib 4.0 mg54.0051.26

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Number of Participants With Best Organ Response to Treatment Based on Investigators Assessment

Organ response rate was estimated as the number of participants with documented organ response (ie. Heart or kidney ). Treatment response of amyloid-related organs were identified based on national cancer institute, common terminology criteria for adverse events (NCI CTCAE) Version 4.02 criteria. (NCT01318902)
Timeframe: At Cycles 3, 6, 9, and 12; every 6 months thereafter until disease progression or the initiation of subsequent antineoplastic therapy and at end of treatment (EOT) visit (Up to approximately 12 months)

InterventionParticipants (Count of Participants)
Dose Escalation Cohort: Ixazomib 4.0 mg2
Dose Escalation Cohort: Ixazomib 5.5 mg0
Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)2
Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)2

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Ctrough: Plasma Concentration Immediately Prior to Dosing for Ixazomib

(NCT01318902)
Timeframe: Cycle 1: Day 1 (MTD cohort participants only, 4.0 mg) and Day 15 (all participants enrolled in the study): predose (within 1 hour (hr) before dosing), and postdose at multiple timepoints up to 168 hr

Interventionng/mL (Mean)
Cycle 1, Day 1Cycle 1, Day 15
Ixazomib 4.0 mg2.15392.9140

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Emax: Maximum Observed Percent Inhibition of Whole Blood 20S Proteasome

(NCT01318902)
Timeframe: Cycle 1: Day 1 (MTD cohort participants only, 4.0 mg) and Day 15 (all participants enrolled in the study): predose (within 1 hour (hr) before dosing), and postdose at multiple timepoints up to 168 hr

Interventionpercentage of inhibition (Mean)
Cycle 1, Day 1Cycle 1, Day 15
Ixazomib 4.0 mg54.1061.09

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Organ Disease Progression-Free Survival (PFS)

Organ disease PFS, measured as the time from the date of the first dose of ixazomib to the date of organ disease progression or death. (NCT01318902)
Timeframe: From the date of the first dose of ixazomib to the date of organ disease progression or death (Up to approximately 12 months)

Interventionmonths (Median)
Dose Escalation Cohort: Ixazomib 4.0 mgNA
Dose Escalation Cohort: Ixazomib 5.5 mgNA
Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)NA
Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)NA

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Number of Participants With Peripheral Neuropathy Reported as a TEAE

Neurotoxicity was assessed as the number of participants with the TEAE of peripheral neuropathy. (NCT01318902)
Timeframe: From the first dose of study drug plus 30 days after last dose of study drug or until the initiation of subsequent antineoplastic therapy (Up to approximately 13 months)

,,,
InterventionParticipants (Count of Participants)
Peripheral sensory neuropathyNeuropathy peripheral
Dose Escalation Cohort: Ixazomib 4.0 mg11
Dose Escalation Cohort: Ixazomib 5.5 mg00
Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)10
Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)10

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Percentage of Participants With One Year Hematologic Disease PFS

One-year survival, defined as the patient survival probability at 1 year after the date of first dose of ixazomib. (NCT01318902)
Timeframe: From the date of the first dose of ixazomib to the date of hematologic disease progression or death (Up to 1 year)

Interventionpercentage of participants (Number)
Dose Escalation Cohort: Ixazomib 4.0 mg83.3
Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)80.0
Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)21.5

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Time to First Hematologic Response

Time to first hematologic response, measured as the time from the first dose of ixazomib to the date of first documentation of a hematologic response. (NCT01318902)
Timeframe: From the date of the first dose of ixazomib to the date of first documentation of a hematologic response (Up to approximately 12 months)

Interventionmonths (Median)
Dose Escalation Cohort: Ixazomib 4.0 mg0.79
Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)3.45
Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)2.11

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Time to Hematologic Disease Progression

Time to hematologic progression, measured as the time from the date of the first dose of ixazomib to the date of first documented hematologic disease progression. (NCT01318902)
Timeframe: From the date of the first dose of ixazomib to the date of first documented hematologic disease progression (Up to approximately 12 months)

Interventionmonths (Median)
Dose Escalation Cohort: Ixazomib 4.0 mg14.8
Dose Escalation Cohort: Ixazomib 5.5 mgNA
Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)73.0
Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)8.3

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Time to Organ Disease Progression

Time to organ disease progression, measured as the time from the date of the first dose of ixazomib to the date of first documented organ disease progression. (NCT01318902)
Timeframe: From the date of the first dose of ixazomib to the date of first documented organ disease progression (Up to approximately 12 months)

Interventionmonths (Median)
Dose Escalation Cohort: Ixazomib 4.0 mg11
Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)12.85
Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)25.15

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AUC0-168: Area Under the Plasma Concentration-time Curve From Time 0 to 168 Hours Post-dose for Ixazomib

(NCT01318902)
Timeframe: Cycle 1: Day 1 (MTD cohort participants only, 4.0 mg) and Day 15 (all participants enrolled in the study): predose (within 1 hour (hr) before dosing), and postdose at multiple timepoints up to 168 hr

Interventionhr*ng/mL (Mean)
Cycle 1, Day 15
Ixazomib 5.5 mg1725.0

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Number of Participants With Clinically Significant Abnormal Laboratory Values Reported as TEAE

The number of participants with any clinically significant abnormal standard safety laboratory values collected throughout the study reported as TEAEs. Parameters assessed were hematology, serum chemistry and urinalysis. Abnormal laboratory values were assessed as an AE if that value leads to discontinuation or delay in treatment, dose modification, therapeutic intervention, or is considered by the investigator to be a clinically significant change from baseline. (NCT01318902)
Timeframe: From the first dose of study drug plus 30 days after last dose of study drug or until the initiation of subsequent antineoplastic therapy (Up to approximately 13 months)

,,,
InterventionParticipants (Count of Participants)
ThrombocytopeniaAnaemiaNeutropeniaHyponatraemiaHypokalaemiaBlood creatinine increasedPlatelet count decreased
Dose Escalation Cohort: Ixazomib 4.0 mg2201110
Dose Escalation Cohort: Ixazomib 5.5 mg0000002
Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)2011110
Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)2201000

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Ctrough: Plasma Concentration Immediately Prior to Dosing for Ixazomib

(NCT01318902)
Timeframe: Cycle 1: Day 1 (MTD cohort participants only, 4.0 mg) and Day 15 (all participants enrolled in the study): predose (within 1 hour (hr) before dosing), and postdose at multiple timepoints up to 168 hr

Interventionng/mL (Mean)
Cycle 1, Day 15
Ixazomib 5.5 mg5.3300

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AUC0-168: Area Under the Plasma Concentration-time Curve From Time 0 to 168 Hours Post-dose for Ixazomib

(NCT01318902)
Timeframe: Cycle 1: Day 1 (MTD cohort participants only, 4.0 mg) and Day 15 (all participants enrolled in the study): predose (within 1 hour (hr) before dosing), and postdose at multiple timepoints up to 168 hr

Interventionhr*ng/mL (Mean)
Cycle 1, Day 1Cycle 1, Day 15
Ixazomib 4.0 mg861.01078.1

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Tmax: Time of First Occurrence of Cmax for Ixazomib

(NCT01318902)
Timeframe: Cycle 1: Day 1 (MTD cohort participants only, 4.0 mg) and Day 15 (all participants enrolled in the study): predose (within 1 hour (hr) before dosing), and postdose at multiple timepoints up to 168 hr

Interventionhours (Median)
Cycle 1, Day 15
Ixazomib 5.5 mg0.7500

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Tmax: Time of First Occurrence of Cmax for Ixazomib

(NCT01318902)
Timeframe: Cycle 1: Day 1 (MTD cohort participants only, 4.0 mg) and Day 15 (all participants enrolled in the study): predose (within 1 hour (hr) before dosing), and postdose at multiple timepoints up to 168 hr

Interventionhours (Median)
Cycle 1, Day 1Cycle 1, Day 15
Ixazomib 4.0 mg1.00001.0000

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AUE0-168: Area Under Effect Curve of Whole Blood 20S Proteasome Inhibition From Zero to Concentration at 168 Hours for Ixazomib

(NCT01318902)
Timeframe: Cycle 1: Day 1 (MTD cohort participants only, 4.0 mg) and Day 15 (all participants enrolled in the study): predose (within 1 hour (hr) before dosing), and postdose at multiple timepoints up to 168 hr

Interventionhr*percentage of inhibition (Mean)
Cycle 1, Day 1Cycle 1, Day 15
Ixazomib 4.0 mg3333.63943.0

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Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)

An AE is any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. An SAE is any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of present hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect or is a medically important event that may not be immediately life-threatening or result in death or hospitalization, but may jeopardize the participant or may require intervention to prevent one of other outcomes listed in definition above, or involves suspected transmission via a medicinal product of an infectious agent. A TEAE is defined as an AE that occurs after administration of first dose of study drug and through 30 days after last dose of study drug or until start of subsequent antineoplastic therapy. (NCT01318902)
Timeframe: From the first dose of study drug plus 30 days after last dose of study drug or until the initiation of subsequent antineoplastic therapy (Up to approximately 13 months)

,,,
InterventionParticipants (Count of Participants)
TEAESAE
Dose Escalation Cohort: Ixazomib 4.0 mg63
Dose Escalation Cohort: Ixazomib 5.5 mg55
Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)105
Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)55

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Duration of Hematologic Response

Duration of hematologic response, measured as the time from the date of first documentation of a hematologic response to the date of hematologic disease progression. (NCT01318902)
Timeframe: From the date of first documentation of a hematologic response to the date of hematologic disease progression (Up to approximately 12 months)

Interventionmonths (Median)
Dose Escalation Cohort: Ixazomib 4.0 mg12.9
Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)69.5
Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)19.7

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Cmax: Maximum Observed Plasma Concentration for Ixazomib

(NCT01318902)
Timeframe: Cycle 1: Day 1 (MTD cohort participants only, 4.0 mg) and Day 15 (all participants enrolled in the study): predose (within 1 hour (hr) before dosing), and postdose at multiple timepoints up to 168 hr

Interventionng/mL (Mean)
Cycle 1, Day 15
Ixazomib 5.5 mg92.20

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Time to First Organ Response

Time to first organ response, measured as the time from the first dose of ixazomib to the date of first documentation of a organ response. (NCT01318902)
Timeframe: From the date of the first dose of ixazomib to the date of first documentation of a organ response (Up to approximately 12 months)

Interventionmonths (Median)
Dose Escalation Cohort: Ixazomib 4.0 mg6.85
Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)9.55
Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)6.85

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Duration of Organ Response

Duration of organ response, measured as the time from the date of first documentation of a organ response to the date of organ disease progression. (NCT01318902)
Timeframe: From the date of first documentation of a organ response to the date of organ disease progression (Up to approximately 12 months)

Interventionmonths (Median)
Dose Escalation Cohort: Ixazomib 4.0 mg4.1
Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)20.5
Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)18.25

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Hematologic Disease Progression-Free Survival (PFS)

Hematologic disease PFS, measured as the time from the date of the first dose of ixazomib to the date of hematologic disease progression or death. (NCT01318902)
Timeframe: From the date of the first dose of ixazomib to the date of hematologic disease progression or death (Up to approximately 12 months)

Interventionmonths (Median)
Dose Escalation Cohort: Ixazomib 4.0 mg14.8
Dose Escalation Cohort: Ixazomib 5.5 mg7.2
Dose Expansion Cohort: Ixazomib 4.0 mg (PI Naive)73.0
Dose Expansion Cohort: Ixazomib 4.0 mg (PI Exposed)8.3

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Maximum Tolerated Dose (MTD) of Ixazomib

MTD was highest dose of Ixazomib, at which <=1 of 6 participants experienced dose-limiting toxicity (DLT). DLT was defined using National Cancer Institute Common Terminology Criteria for Adverse Events, v 4.03 as: Grade 4 neutropenia (absolute neutrophil count <500 cells/mm^3) for >7 days;Grade 3 neutropenia with fever or infection;Grade 4 thrombocytopenia (platelets < 25,000/mm^3) for >7 days;Grade 3 thrombocytopenia with clinically significant bleeding;platelet count <10,000/mm^3;Grade 2 peripheral neuropathy with pain or >=Grade 3 peripheral neuropathy; >=Grade 3 nausea/emesis, diarrhea controlled by supportive therapy;Grade 3 QTc prolongation (QTc >500 msec);any >=Grade 3 nonhematologic toxicity except Grade 3 arthralgia/myalgia;or <1 week Grade 3 fatigue;delay in initiation of the subsequent therapy cycle by >2 weeks;other >=Grade 2 study drug-related nonhematologic toxicities requiring therapy discontinuation, considered possibly related to therapy as assessed by Investigator. (NCT01318902)
Timeframe: Cycle 1 (28 days)

Interventionmg (Number)
Dose Escalation Cohort: Ixazomib 4.0 mg4
Dose Escalation Cohort: Ixazomib 5.5 mg4

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TEmax: Time to Maximum Observed Effect (Emax) of Whole Blood 20S Proteasome Inhibition for Ixazomib

(NCT01318902)
Timeframe: Cycle 1: Day 1 (MTD cohort participants only, 4.0 mg) and Day 15 (all participants enrolled in the study): predose (within 1 hour (hr) before dosing), and postdose at multiple timepoints up to 168 hr

Interventionhours (Median)
Cycle 1, Day 1Cycle 1, Day 15
Ixazomib 4.0 mg1.00001.0300

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Terminal Elimination Rate Constant (λz) for Ixazomib (Phase 1)

Terminal elimination rate constant, calculated as the negative of the slope of the log-linear regression of the natural logarithm concentration-time curve during the terminal phase. (NCT01335685)
Timeframe: Pre-dose on Day 1 and at multiple timepoints (up to 8 hours) on Day 11 for Arm A, Day 15 for Arm B and Day 29 for Arms C and D

,,
Intervention1/hour (Mean)
Cycle 1, Day 15
Arm B: Ixazomib 3.0 mg0.004
Arm B: Ixazomib 4.0 mg0.006
Arm B: Ixazomib 5.5 mg0.007

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Terminal Elimination Rate Constant (λz) for Ixazomib (Phase 1)

Terminal elimination rate constant, calculated as the negative of the slope of the log-linear regression of the natural logarithm concentration-time curve during the terminal phase. (NCT01335685)
Timeframe: Pre-dose on Day 1 and at multiple timepoints (up to 8 hours) on Day 11 for Arm A, Day 15 for Arm B and Day 29 for Arms C and D

,
Intervention1/hour (Mean)
Cycle 1, Day 29
Arm C: Ixazomib 4.0 mg0.005
Arm D: Ixazomib 4.0 mg0.006

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Terminal Elimination Rate Constant (λz) for Ixazomib (Phase 1)

Terminal elimination rate constant, calculated as the negative of the slope of the log-linear regression of the natural logarithm concentration-time curve during the terminal phase. (NCT01335685)
Timeframe: Pre-dose on Day 1 and at multiple timepoints (up to 8 hours) on Day 11 for Arm A, Day 15 for Arm B and Day 29 for Arms C and D

Intervention1/hour (Mean)
Cycle 1, Day 15Cycle 1, Day 29
Arm C: Ixazomib 3.0 mgNA0.005

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Terminal Phase Elimination Half-life (T1/2) for Ixazomib (Phase 1)

Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma. (NCT01335685)
Timeframe: Pre-dose on Day 1 and at multiple timepoints (up to 8 hours) on Day 11 for Arm A, Day 15 for Arm B and Day 29 for Arms C and D

,,
Interventionhours (Mean)
Cycle 1, Day 15
Arm B: Ixazomib 3.0 mg167.000
Arm B: Ixazomib 4.0 mg130.362
Arm B: Ixazomib 5.5 mg98.900

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Terminal Phase Elimination Half-life (T1/2) for Ixazomib (Phase 1)

Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma. (NCT01335685)
Timeframe: Pre-dose on Day 1 and at multiple timepoints (up to 8 hours) on Day 11 for Arm A, Day 15 for Arm B and Day 29 for Arms C and D

,
Interventionhours (Mean)
Cycle 1, Day 29
Arm C: Ixazomib 4.0 mg163.500
Arm D: Ixazomib 4.0 mg120.050

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Terminal Phase Elimination Half-life (T1/2) for Ixazomib (Phase 1)

Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma. (NCT01335685)
Timeframe: Pre-dose on Day 1 and at multiple timepoints (up to 8 hours) on Day 11 for Arm A, Day 15 for Arm B and Day 29 for Arms C and D

Interventionhours (Mean)
Cycle 1, Day 15Cycle 1, Day 29
Arm C: Ixazomib 3.0 mgNA140.575

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Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib (Phase 1)

(NCT01335685)
Timeframe: Pre-dose on Day 1 and at multiple timepoints (up to 8 hours) on Day 11 for Arm A, Day 15 for Arm B and Day 29 for Arms C and D

,
Interventionhours (Median)
Cycle 1, Day 1Cycle 1, Day 11
Arm A: Ixazomib 3.0 mg1.0201.050
Arm A: Ixazomib 3.7 mg0.5178.000

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Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib (Phase 1)

(NCT01335685)
Timeframe: Pre-dose on Day 1 and at multiple timepoints (up to 8 hours) on Day 11 for Arm A, Day 15 for Arm B and Day 29 for Arms C and D

,,
Interventionhours (Median)
Cycle 1, Day 1Cycle 1, Day 15
Arm B: Ixazomib 3.0 mg1.7500.833
Arm B: Ixazomib 4.0 mg1.0001.000
Arm B: Ixazomib 5.5 mg1.3020.500

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Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib (Phase 1)

(NCT01335685)
Timeframe: Pre-dose on Day 1 and at multiple timepoints (up to 8 hours) on Day 11 for Arm A, Day 15 for Arm B and Day 29 for Arms C and D

,,
Interventionhours (Median)
Cycle 1, Day 1Cycle 1, Day 29
Arm C: Ixazomib 3.0 mg1.5601.500
Arm C: Ixazomib 4.0 mg1.2821.275
Arm D: Ixazomib 4.0 mg0.5670.760

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AUCtau: Area Under the Plasma Concentration-time Curve Over the Dosing Interval for Ixazomib (Phase 1)

(NCT01335685)
Timeframe: Pre-dose on Day 1 and at multiple timepoints (up to 8 hours) on Day 11 for Arm A, Day 15 for Arm B and Day 29 for Arms C and D

,
Interventionhr*ng/mL (Mean)
Cycle 1, Day 1Cycle 1, Day 11
Arm A: Ixazomib 3.0 mg319.7141227.143
Arm A: Ixazomib 3.7 mg287.0001180.000

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Duration of Response (DOR) (Phase 2)

DOR is defined as time of first documentation of a confirmed PR or better response to first documented PD or start of alternative therapy. DOR was presented for those achieving CR+VGPR+PR. Per IMWG criteria, CR:1)Negative immunofixation on serum+urine, 2)Disappearance of any soft tissue plasmacytomas, 3)< 5% plasma cells in bone marrow. VGPR: Serum+urine M-protein detectable by immunofixation but not on electrophoresis/ 90% or >reduction in serum M-protein + urine M-protein level < 100 mg/ 24-hour. PR:1)≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24-hour. If serum+urine M-protein are unmeasurable, ≥50% decrease in difference between involved and uninvolved FLC levels is required. Else, ≥50% reduction in plasma cells is required in place of M-protein, provided baseline bone marrow plasma cell percentage was ≥30%. In addition, if present at baseline, a ≥50% reduction in size of soft tissue plasmacytomas is required. (NCT01335685)
Timeframe: From the time from the date of first documentation of PR or better to the date of first documented disease progression for up to 5.5 years

Interventionmonths (Median)
Arm B: Ixazomib 4.0 mg (RP2D)25.2

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Overall Response Rate (ORR)

ORR is defined as percentage of participants with overall response including CR, VGPR, and partial response (PR). Per IMWG criteria, CR:1)Negative immunofixation on serum and urine, 2)Disappearance of any soft tissue plasmacytomas, 3)< 5% plasma cells in bone marrow. VGPR: Serum+urine M-protein detectable by immunofixation but not on electrophoresis/ 90% or >reduction in serum M-protein + urine M-protein level < 100 mg/ 24-hour. PR:1)≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24-hour. If serum+urine M-protein are unmeasurable, ≥50% decrease in difference between involved and uninvolved FLC levels is required. If serum+urine M-protein are unmeasurable and serum free light assay is also unmeasurable, ≥50% reduction in plasma cells is required in place of M-protein, provided baseline bone marrow plasma cell percentage was ≥30%. In addition, if present at baseline, a ≥50% reduction in size of soft tissue plasmacytomas is required. (NCT01335685)
Timeframe: Day 1 of every other cycle from Day 1 of Cycle 2 (each cycle of 28 days) up to 61 cycles, at end of treatment (Up to 5.5 years)

Interventionpercentage of participants (Number)
Arm A: Ixazomib 3.0 mg86
Arm A: Ixazomib 3.7 mg67
Arm B: Ixazomib 3.0 mg100
Arm B: Ixazomib 4.0 mg65
Arm B: Ixazomib 5.5 mg60
Arm C: Ixazomib 3.0 mg40
Arm C: Ixazomib 4.0 mg67
Arm D: Ixazomib 4.0 mg50

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Overall Survival (Phase 2)

Overall Survival is the time in months from start of study treatment to date of death due to any cause. (NCT01335685)
Timeframe: From date of enrollment to date of death, approximately 5.5 years (Approximate median follow-up: 43.6 months)

Interventionmonths (Median)
Arm B: Ixazomib 4.0 mg (RP2D)NA

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Progression Free Survival (Phase 2)

Progression Free Survival is defined as time in months from start of study treatment to first documentation of objective tumor progression per investigator assessment or up to death due to any cause, whichever occurs first. Per IMWG criteria, progressive disease requires any 1 or more of following: Increase of ≥25% from nadir in serum M-component and/or (absolute increase must be ≥0.5 g/dL), urine M-component and/or (absolute increase must be ≥200 mg/24 hour. Participants without measurable serum+urine M-protein levels: difference between involved and uninvolved FLC levels. The absolute increase must be >10 mg/dL. Bone marrow plasma cell percentage: absolute % must be ≥10%. Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in size of existing bone lesions or soft tissue plasmacytomas. Development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.85 mmol/L) that can be attributed solely to plasma cell proliferative disorder. (NCT01335685)
Timeframe: From the date of enrollment to the date of the first documented disease progression or death due to any cause for up to 5.5 years

Interventionmonths (Median)
Arm B: Ixazomib 4.0 mg (RP2D)18.4

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Time to First Response (Phase 2)

Response is defined as CR, VGPR and PR. Per IMWG criteria, CR:1)Negative immunofixation on serum+urine, 2)Disappearance of any soft tissue plasmacytomas, 3)< 5% plasma cells in bone marrow. VGPR: Serum+urine M-protein detectable by immunofixation but not on electrophoresis/ 90% or >reduction in serum M-protein + urine M-protein level < 100 mg/ 24-hour. PR:1)≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24-hour. If serum+urine M-protein are unmeasurable, ≥50% decrease in difference between involved and uninvolved FLC levels is required. Else, ≥50% reduction in plasma cells is required in place of M-protein, provided baseline bone marrow plasma cell percentage was ≥30%. In addition, if present at baseline, a ≥50% reduction in size of soft tissue plasmacytomas is required. (NCT01335685)
Timeframe: From the date of enrollment to the date of the first documented response for up to 5.5 years

Interventionmonths (Median)
Arm B: Ixazomib 4.0 mg (RP2D)1.9

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Time to Progression (TTP) (Phase 2)

TTP is defined as time from date of enrollment to date of first documented disease progression (PD). Per IMWG criteria, progressive disease requires any 1 or more of following: Increase of ≥25% from nadir in serum M-component and/or (absolute increase must be ≥0.5 g/dL), urine M-component and/or (absolute increase must be ≥200 mg/24 hour. Participants without measurable serum+urine M-protein levels: difference between involved and uninvolved FLC levels. The absolute increase must be >10 mg/dL. Bone marrow plasma cell percentage: absolute % must be ≥10%. Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in size of existing bone lesions or soft tissue plasmacytomas. Development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.85 mmol/L) that can be attributed solely to plasma cell proliferative disorder. (NCT01335685)
Timeframe: From the date of enrollment to the date of the first documented disease progression for up to 5.5 years

Interventionmonths (Median)
Arm B: Ixazomib 4.0 mg (RP2D)22.1

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Very Good Partial Response (VGPR) or Better Response Rate (Phase 2)

VGPR or better response rate is defined as percentage of participants with a complete response (CR) and very good partial response (VGPR). Per International Myeloma Working Group Uniform Response Criteria (IMWG), CR: 1) Negative immunofixation on the serum and urine, 2) Disappearance of any soft tissue plasmacytomas and 3) < 5% plasma cells in bone marrow. VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hour. (NCT01335685)
Timeframe: Day 1 of every other cycle from Day 1 of Cycle 2 (each cycle of 28 days) until death (Up to 5.5 years)

Interventionpercentage of participants (Number)
Arm B: Ixazomib 4.0 mg (RP2D)48

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AUCtau: Area Under the Plasma Concentration-time Curve Over the Dosing Interval for Ixazomib (Phase 1)

(NCT01335685)
Timeframe: Pre-dose on Day 1 and at multiple timepoints (up to 8 hours) on Day 11 for Arm A, Day 15 for Arm B and Day 29 for Arms C and D

,,
Interventionhr*ng/mL (Mean)
Cycle 1, Day 1Cycle 1, Day 15
Arm B: Ixazomib 3.0 mg450.000705.667
Arm B: Ixazomib 4.0 mg806.8241610.500
Arm B: Ixazomib 5.5 mg1612.2501680.000

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AUCtau: Area Under the Plasma Concentration-time Curve Over the Dosing Interval for Ixazomib (Phase 1)

(NCT01335685)
Timeframe: Pre-dose on Day 1 and at multiple timepoints (up to 8 hours) on Day 11 for Arm A, Day 15 for Arm B and Day 29 for Arms C and D

,,
Interventionhr*ng/mL (Mean)
Cycle 1, Day 1Cycle 1, Day 29
Arm C: Ixazomib 3.0 mg662.8331527.800
Arm C: Ixazomib 4.0 mg1037.5002680.000
Arm D: Ixazomib 4.0 mg934.8002435.000

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Cmax: Maximum Observed Plasma Concentration for Ixazomib (Phase 1)

(NCT01335685)
Timeframe: Pre-dose on Day 1 and at multiple timepoints (up to 8 hours) on Day 11 for Arm A, Day 15 for Arm B and Day 29 for Arms C and D

,
Interventionng/mL (Mean)
Cycle 1, Day 1Cycle 1, Day 11
Arm A: Ixazomib 3.0 mg26.79169.214
Arm A: Ixazomib 3.7 mg39.30022.000

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Cmax: Maximum Observed Plasma Concentration for Ixazomib (Phase 1)

(NCT01335685)
Timeframe: Pre-dose on Day 1 and at multiple timepoints (up to 8 hours) on Day 11 for Arm A, Day 15 for Arm B and Day 29 for Arms C and D

,,
Interventionng/mL (Mean)
Cycle 1, Day 1Cycle 1, Day 15
Arm B: Ixazomib 3.0 mg22.95030.267
Arm B: Ixazomib 4.0 mg53.27885.636
Arm B: Ixazomib 5.5 mg104.225285.000

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Cmax: Maximum Observed Plasma Concentration for Ixazomib (Phase 1)

(NCT01335685)
Timeframe: Pre-dose on Day 1 and at multiple timepoints (up to 8 hours) on Day 11 for Arm A, Day 15 for Arm B and Day 29 for Arms C and D

,,
Interventionng/mL (Mean)
Cycle 1, Day 1Cycle 1, Day 29
Arm C: Ixazomib 3.0 mg55.36759.560
Arm C: Ixazomib 4.0 mg50.875109.000
Arm D: Ixazomib 4.0 mg72.080146.400

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Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. (NCT01335685)
Timeframe: From first dose of study drug through 30 days after last dose of study drug or until the start of subsequent antineoplastic therapy for up to 5.6 years

,,,,,,,
Interventionparticipants (Number)
During Entire Study Any Adverse EventGrade 3 or Higher Adverse EventSerious Adverse EventAdverse Event With Any Study Drug DiscontinuationAdverse Event With Any Study Drug Reduction
Arm A: Ixazomib 3.0 mg77204
Arm A: Ixazomib 3.7 mg44402
Arm B: Ixazomib 3.0 mg33301
Arm B: Ixazomib 4.0 mg262112813
Arm B: Ixazomib 5.5 mg55323
Arm C: Ixazomib 3.0 mg65423
Arm C: Ixazomib 4.0 mg44212
Arm D: Ixazomib 4.0 mg65124

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Observed Accumulation Ratio for AUCtau (Rac) (Phase 1)

Accumulation ratio for AUCtau (Rac) was calculated as area under the curve from time zero to end of dosing interval (AUCtau) on Day 14 divided by area under the curve from time zero to end of dosing interval (AUCtau) on Day 1. (NCT01335685)
Timeframe: Pre-dose on Day 1 and at multiple timepoints (up to 8 hours) on Day 11 for Arm A, Day 15 for Arm B and Day 29 for Arms C and D

,
Interventionratio (Mean)
Cycle 1, Day 11
Arm A: Ixazomib 3.0 mg4.019
Arm A: Ixazomib 3.7 mg4.120

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Observed Accumulation Ratio for AUCtau (Rac) (Phase 1)

Accumulation ratio for AUCtau (Rac) was calculated as area under the curve from time zero to end of dosing interval (AUCtau) on Day 14 divided by area under the curve from time zero to end of dosing interval (AUCtau) on Day 1. (NCT01335685)
Timeframe: Pre-dose on Day 1 and at multiple timepoints (up to 8 hours) on Day 11 for Arm A, Day 15 for Arm B and Day 29 for Arms C and D

,,
Interventionratio (Mean)
Cycle 1, Day 15
Arm B: Ixazomib 3.0 mg1.700
Arm B: Ixazomib 4.0 mg2.288
Arm B: Ixazomib 5.5 mg1.970

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Observed Accumulation Ratio for AUCtau (Rac) (Phase 1)

Accumulation ratio for AUCtau (Rac) was calculated as area under the curve from time zero to end of dosing interval (AUCtau) on Day 14 divided by area under the curve from time zero to end of dosing interval (AUCtau) on Day 1. (NCT01335685)
Timeframe: Pre-dose on Day 1 and at multiple timepoints (up to 8 hours) on Day 11 for Arm A, Day 15 for Arm B and Day 29 for Arms C and D

,,
Interventionratio (Mean)
Cycle 1, Day 29
Arm C: Ixazomib 3.0 mg2.632
Arm C: Ixazomib 4.0 mg2.560
Arm D: Ixazomib 4.0 mg2.540

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Overall Survival

Overall survival was measured as the time from the date of first dose of study treatment to the time of death plus 1 day. For participants who did not die, survival was censored at the date of last contact. Overall Survival was analyzed using standard survival analysis techniques based on Kaplan-Meier estimates. (NCT01383928)
Timeframe: Baseline up to a follow-up of 62.1 months

Interventionmonths (Median)
Ixazomib 3 mgNA

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Kaplan-Meier Estimate of Percentage of Participants Achieving Survival at Year 1

The Kaplan-Meier estimate reports the percentage of participants surviving at Year 1. (NCT01383928)
Timeframe: 1 year after the first dose of study treatment

Interventionpercentage of participants (Number)
Ixazomib 3 mg94

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Phase 1: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib

Tmax: Time to reach the first maximum plasma concentration (Cmax), equal to time (hours) to Cmax of ixazomib after administration, obtained directly from the plasma concentration-time curve. (NCT01383928)
Timeframe: Cycle 1, Days 1 and 11

,
Interventionhours (Median)
Day 1Day 11
Phase 1: Ixazomib 3 mg1.0351.030
Phase 1: Ixazomib 3.7 mg1.0000.984

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Phase 1: Percentage of Participants Experiencing 1 or More Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs)

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. (NCT01383928)
Timeframe: Baseline up to 30 days after last dose of study drug (Up to Cycle 83 - approximately 2067 days)

,
Interventionpercentage of participants (Number)
Adverse EventSerious Adverse Event
Phase 1: Ixazomib 3 mg10071
Phase 1: Ixazomib 3.7 mg10029

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Phase 1: Number of Participants With Markedly Abnormal Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs)

Laboratory tests included chemistry, hematology and urinalysis. Abnormal laboratory value was assessed as an AE if the value lead to discontinuation or delay in treatment, dose modification, therapeutic intervention, or was considered by the investigator to be a clinically significant change from baseline. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. (NCT01383928)
Timeframe: Baseline up to 30 days after last dose of study drug (Up to Cycle 83 - approximately 2067 days)

,
InterventionParticipants (Count of Participants)
Alanine aminotransferase increasedAspartate aminotransferase increasedBlood creatinine increasedShift to the leftPlatelet count decreasedBlood bicarbonate decreasedAnaemiaNeutropeniaThrombocytopeniaEosinophiliaHypokalaemiaHyperkalaemiaHyperglycaemiaHyponatraemiaHypomagnesaemiaHyperchloraemiaIron deficiency anaemia
Phase 1: Ixazomib 3 mg00201111101140011
Phase 1: Ixazomib 3.7 mg32010000110001200

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Phase 1: Number of Participants With Clinically Significant Change From Baseline in Vital Signs

Vital signs included body temperature, blood pressure and heart rate. (NCT01383928)
Timeframe: Baseline up to 30 days after last dose of study drug (Up to Cycle 83 - approximately 2067 days)

,
InterventionParticipants (Count of Participants)
PyrexiaBradycardiaOrthostatic hypotensionHypotension
Phase 1: Ixazomib 3 mg1101
Phase 1: Ixazomib 3.7 mg3011

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Phase 1: Cmax: Maximum Plasma Concentration for Ixazomib

Maximum observed plasma concentration (Cmax) is the peak plasma concentration of ixazomib, obtained directly from the plasma concentration-time curve. (NCT01383928)
Timeframe: Cycle 1, Days 1 and 11

,
Interventionnanogram per milliliter (ng/mL) (Geometric Mean)
Day 1Day 11
Phase 1: Ixazomib 3 mg33.51558.674
Phase 1: Ixazomib 3.7 mg46.94651.832

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Phase 1: AUC(0-72): Area Under the Plasma Concentration-Time Curve From Time 0 to 72 Hours Postdose for Ixazomib

AUC(0-72) is a measure of the area under the plasma concentration time-curve from time zero to 72 hours post-dose for ixazomib. (NCT01383928)
Timeframe: Cycle 1, Days 1 and 11

,
Interventionhour*nanogram per milliliter (hr*ng/mL) (Geometric Mean)
Day 1Day 11
Phase 1: Ixazomib 3 mg315.4501105.44
Phase 1: Ixazomib 3.7 mg284.5761023.52

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Time to Disease Progression (TTP)

Time to progression was defined as the time from the date of first dose of study treatment to the date of first documentation of PD + 1 day. Participants that did not experience PD will be censored at the last response assessment that is SD or better. PD: >=25% increase from lowest value in:serum/urine M-component; difference between involved, uninvolved FLC levels; bone marrow plasma cell percent; new bone lesions/soft tissue plasmacytomas development/existing bone lesions/soft tissue plasmacytomas size rise; hypercalcaemia development. SD: not meeting criteria for CR, VGPR, PR, or PD. Participants that received Autologous Stem Cell Transplantation (ASCT) or an alternate cancer therapy were also be censored at the last response assessment that is, SD or better prior to initiation of therapy. Participants without response assessment will be censored at the date of first dose. TTP was analyzed using standard survival analysis techniques based on Kaplan-Meier estimates. (NCT01383928)
Timeframe: Baseline up to a follow-up of 62.1 months

Interventionmonths (Median)
Ixazomib 3 mg29.7

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Progression Free Survival (PFS)

PFS was defined as the time from the date of first dose of study treatment to the date of first documentation of progressive disease or to death due to any cause, whichever occurred first plus 1. PD: >=25% increase from lowest value in:serum/urine M-component; difference between involved,uninvolved FLC levels; bone marrow plasma cell percent; new bone lesions/soft tissue plasmacytomas development/existing bone lesions/soft tissue plasmacytomas size rise; hypercalcaemia development. SD: not meeting criteria for CR, VGPR, PR, or PD. Participants who received ASCT or an alternate anticancer therapy were censored at the last response assessment that was SD or better before initiation of therapy. Participants without a response assessment were censored at the date of first dose. PFS was analyzed using standard survival analysis techniques based on Kaplan-Meier estimates. (NCT01383928)
Timeframe: Baseline up to a follow-up of 62.1 months

Interventionmonths (Median)
Ixazomib 3 mg29.7

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Phase 2: Time to Response

Time to first response is defined as the time from the date of first dose of study treatment to the date of the first documentation of a confirmed response (PR or better) in a participant who responded + 1 day. PR as per IMWG criteria is 50% reduction of serum M-protein and reduction in 24-h urinary M-protein by 90% or to <200 mg per 24 hours. (NCT01383928)
Timeframe: Baseline until end of treatment (Up to treatment Cycle 74 - approximately 1875 days)

Interventionmonths (Median)
Phase 2: Ixazomib 3 mg0.72

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Phase 2: Percentage of Participants With Very Good Partial Response (VGPR)

VGPR as per IMWG criteria is serum and urine M-protein detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein plus urine M-protein level <100 mg per 24 hours. (NCT01383928)
Timeframe: Baseline until end of treatment (Up to treatment Cycle 74 - approximately 1875 days)

Interventionpercentage of participants (Number)
Phase 2: Ixazomib 3 mg37

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Phase 2: Percentage of Participants With Treatment-Emergent Adverse Events Resulting in Study Drug Discontinuation

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. (NCT01383928)
Timeframe: Baseline up to 30 days after the last dose of study drug (approximately 1905 days)

Interventionpercentage of participants (Number)
Phase 2: Ixazomib 3 mg14

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Phase 2: Percentage of Participants With Stringent Complete Response (sCR)

sCR as per IMWG criteria is CR plus normal FLC ratio and absence of clonal cells in bone marrow. CR is negative immunofixation on serum and urine and disappearance of soft tissue plasmacytomas and <5% plasma cells in bone marrow. (NCT01383928)
Timeframe: Baseline until end of treatment (Up to treatment Cycle 74 - approximately 1875 days)

Interventionpercentage of participants (Number)
Phase 2: Ixazomib 3 mg22

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Phase 2: Duration of Response (DOR)

DOR was measured as the time from the date of first documentation of a confirmed response to the date of first documented PD. PD is defined as >=25% increase from lowest value in: serum/urine M-component; difference between involved, uninvolved FLC levels; bone marrow plasma cell percent; development of new bone lesions or soft tissue plasmacytomas development or increase in the size of existing bone lesions or soft tissue plasmacytomas; hypercalcaemia development. (NCT01383928)
Timeframe: Baseline until end of treatment (Up to treatment Cycle 74 - approximately 1875 days)

Interventionmonths (Median)
Phase 2: Ixazomib 3 mg29.0

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Phase 2: Percentage of Participants With Partial Response (PR)

PR as per IMWG criteria is 50% reduction of serum M-protein and reduction in 24-hr urinary M-protein by 90% or to <200 mg per 24 hours. (NCT01383928)
Timeframe: Baseline until end of treatment (Up to treatment Cycle 74 - approximately 1875 days)

Interventionpercentage of participants (Number)
Phase 2: Ixazomib 3 mg65

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Phase 2: Percentage of Participants With Overall Response (CR+VGPR+PR)

Overall response is defined as CR, VGPR or PR based on IMWG Response Criteria for malignant lymphoma. CR: disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. VGPR: serum, urine M-protein detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein+urine M-protein level <100 mg/24h. Partial response (PR) is a minimum of 50% decrease in sum of the product of the diameters of up to 6 of the largest dominant nodes or nodal masses and no increase in the size of other nodes. (NCT01383928)
Timeframe: Baseline until end of treatment (Up to treatment Cycle 74 - approximately 1875 days)

Interventionpercentage of participants (Number)
Phase 2: Ixazomib 3 mg94

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Phase 2: Percentage of Participants With Near Complete Response (nCR)

nCR as per IMWG criteria is positive immunofixation analysis of serum or urine as the only evidence of disease; appearance of any soft tissue plasmacytomas and <=5% plasma cells in bone marrow. (NCT01383928)
Timeframe: Baseline until end of treatment (Up to treatment Cycle 74 - approximately 1875 days)

Interventionpercentage of participants (Number)
Phase 2: Ixazomib 3 mg10

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Phase 2: Percentage of Participants With Minimal Response (MR)

MR as per IMWG criteria is 25%-49% reduction in serum paraprotein and 50%-89% reduction in urine light chain excretion for 6 weeks. (NCT01383928)
Timeframe: Baseline until end of treatment (Up to treatment Cycle 74 - approximately 1875 days)

Interventionpercentage of participants (Number)
Phase 2: Ixazomib 3 mg6

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Phase 2: Percentage of Participants With Grade 3 or Higher Adverse Events

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. As per Common Terminology Criteria for Adverse Events v4.0 (CTCAE), Grade 3 = AE with severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4 = AE with life-threatening consequences; urgent intervention indicated and Grade 5 = Death related to AE. (NCT01383928)
Timeframe: Baseline up to 30 days after the last dose of study drug (approximately 1905 days)

Interventionpercentage of participants (Number)
Phase 2: Ixazomib 3 mg74

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Phase 2: Percentage of Participants With Complete Response (CR) + Very Good Partial Response (VGPR)

CR as per International Myeloma Working Group (IMWG) uniform criteria is defined as negative immunofixation on the serum and urine and disappearance of soft tissue plasmacytomas and <5% plasma cells in bone marrow. VGPR as per IMWG criteria is defined as serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100 mg per 24 hours. VGPR was applicable only to participants who had measurable disease defined by at least 1 of the following 3 measurements: Serum M-protein greater than or equal to (>=)1 g/dL; Urine M-protein >=200 mg/24 hours; Serum FLC assay level >=10 mg/dL, provided serum FLC ratio was abnormal. (NCT01383928)
Timeframe: Baseline until end of treatment (Up to treatment Cycle 74 - approximately 1875 days)

Interventionpercentage of participants (Number)
Phase 2: Ixazomib 3 mg65

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Phase 2: Percentage of Participants With Complete Response (CR)

CR as per IMWG criteria is negative immunofixation on serum and urine and disappearance of soft tissue plasmacytomas and <5% plasma cells in bone marrow. (NCT01383928)
Timeframe: Baseline until end of treatment (Up to treatment Cycle 74 - approximately 1875 days)

Interventionpercentage of participants (Number)
Phase 2: Ixazomib 3 mg29

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Phase 2: Percentage of Participants Experiencing Serious Adverse Events

A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event. (NCT01383928)
Timeframe: Baseline up to 30 days after the last dose of study drug (approximately 1905 days)

Interventionpercentage of participants (Number)
Phase 2: Ixazomib 3 mg46

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Phase 1: Percentage of Participants With Best Overall Response

CR as per International Myeloma Working Group (IMWG) uniform criteria is defined as negative immunofixation on the serum and urine and disappearance of soft tissue plasmacytomas and <5% plasma cells in bone marrow. Partial response(PR):>=50% reduction of serum M-protein,urinary M-protein by >=90%/to <200 mg/24 hr reduction.Near CR(nCR):positive immunofixation of serum/urine;soft tissue plasmacytomas disappearance;<=5% plasma cells in bone marrow. VGPR as per IMWG criteria is defined as serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100 mg per 24 hours. VGPR was applicable only to participants who had measurable disease defined by at least 1 of the following 3 measurements: Serum M-protein greater than or equal to (>=)1 g/dL; Urine M-protein >=200 mg/24 hours; Serum FLC assay level >=10 mg/dL, provided serum FLC ratio was abnormal. (NCT01383928)
Timeframe: Baseline until end of study treatment (Up to treatment Cycle 83 - approximately 2037 days)

Interventionpercentage of participants (Number)
Phase 1: Ixazomib 3 mg92

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Phase 1: Rac: Accumulation Ratio of Ixazomib

The accumulation ratio (Rac) was estimated as the ratio of AUC (0-72) on Day 11 to the AUC (0-72) on Day 1. AUC (0-72) is the area under the plasma concentration-time curve from time zero to 72 hours post-dose for ixazomib. (NCT01383928)
Timeframe: Cycle 1, Days 1 and 11

Interventionratio (Geometric Mean)
Phase 1: Ixazomib 3 mg3.785
Phase 1: Ixazomib 3.7 mg3.967

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Phase 2: Percentage of Participants With Complete Response (CR) and Very Good Partial Response (VGPR) After Cycles 4, 8, and 16

CR as per IMWG criteria is defined as negative immunofixation on the serum and urine and disappearance of soft tissue plasmacytomas and <5% plasma cells in bone marrow. VGPR as per IMWG criteria is defined as serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100 mg per 24 hours. VGPR were applicable only to participants who had measurable disease defined by at least 1 of the following 3 measurements: Serum M-protein; Urine M-protein; Serum FLC assay. (NCT01383928)
Timeframe: Cycles 4, 8, and 16

Interventionpercentage of participants (Number)
After 4 cyclesAfter 8 cyclesAfter 16 cycles
Phase 2: Ixazomib 3 mg496492

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Phase 1: Maximum Tolerated Dose (MTD)

MTD was highest dose of ixazomib given with combination drugs, at which <=1 of 6 participants experienced dose-limiting toxicity (DLT) during Cycle 1 of Phase 1. DLT defined as any of following considered possibly related to therapy: Grade 4 neutropenia (absolute neutrophil count [ANC] <500 cell per cubic millimeter [cells/mm^3]) for >7 days; Grade 3 neutropenia with fever or infection; Grade 4 thrombocytopenia for >7 days; Grade 3 thrombocytopenia with clinically significant bleeding; platelet count <10,000/mm^3; Grade 2 peripheral neuropathy with pain or >=Grade 3 peripheral neuropathy; >=Grade 3 nausea/emesis, diarrhea controlled by supportive therapy; any >=Grade 3 nonhematologic toxicity except Grade 3 arthralgia/myalgia; or <1 week Grade 3 fatigue; delay in initiation of the subsequent therapy cycle by >14 days; <=80% lenalidomide doses administered due to other >=Grade 2 combination study drug-related nonhematologic toxicities requiring therapy discontinuation. (NCT01383928)
Timeframe: Cycle 1 (21 days)

Interventionmg (Number)
Phase 1: All Participants3.7

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AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ixazomib

(NCT01454076)
Timeframe: Arm 1:Days 1, 15 and Arm 5:Day 6 pre-dose and at multiple time points(up to 264 hrs)post-dose;Arm 2, 3:Days 1,15 pre-dose and at multiple time points(up to 216 hrs)post-dose;Arm 4:Day 8 pre-dose and at multiple time points(up to 168 hrs)post-dose

Interventionnanogram*hour per milliliter (ng*hr/mL)] (Geometric Mean)
Arm 1: Ixazomib 2.5 mg551.985
Arm 1: Ixazomib 2.5 mg + Ketoconazole 400 mg1148.778
Arm 2: Ixazomib 4 mg Capsule A1284.079
Arm 2: Ixazomib 4 mg Capsule B1334.659
Arm 3: Ixazomib 4 mg Fasted1465.979
Arm 3: Ixazomib 4 mg Fed998.698
Arm 4: Ixazomib 4 mg + Rifampin 600 mg231.527
Arm 5: Ixazomib 2.5 mg + Clarithromycin 500 mg613.112

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Cmax: Maximum Observed Plasma Concentration for Ixazomib

(NCT01454076)
Timeframe: Arm 1:Days 1, 15 and Arm 5:Day 6 pre-dose and at multiple time points(up to 264 hours[hrs])post-dose;Arm 2, 3:Days 1,15 pre-dose and at multiple time points(up to 216 hrs)post-dose;Arm 4:Day 8 pre-dose and at multiple time points(up to 168 hrs)post-dose

Interventionnanogram per milliliter (ng/mL) (Geometric Mean)
Arm 1: Ixazomib 2.5 mg38.975
Arm 1: Ixazomib 2.5 mg + Ketoconazole 400 mg39.250
Arm 2: Ixazomib 4 mg Capsule A61.866
Arm 2: Ixazomib 4 mg Capsule B71.949
Arm 3: Ixazomib 4 mg Fasted77.001
Arm 3: Ixazomib 4 mg Fed22.752
Arm 4: Ixazomib 4 mg + Rifampin 600 mg25.706
Arm 5: Ixazomib 2.5 mg + Clarithromycin 500 mg37.245

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Number of Participants With Clinically Significant Vital Sign Abnormalities

(NCT01454076)
Timeframe: Cycle 1 Day 1 up to 30 days after last dose of study drug (Arm 1 and 5: Cycle 19 Day 45; Arm 2: Cycle 7 Day 45; Arm 3: Cycle 22 Day 45; Arm 4: Cycle 25 Day 45

Interventionparticipants (Number)
Arm 1: Ixazomib 2.5 mg + Ketoconazole 400 mg0
Arm 2: Ixazomib 4 mg Capsule A or B0
Arm 3: Ixazomib 4 mg Fasted or Fed0
Arm 4: Ixazomib 4 mg + Rifampin 600 mg0
Arm 5: Ixazomib 2.5 mg + Clarithromycin 500 mg0

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Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib

(NCT01454076)
Timeframe: Arm 1:Days 1, 15 and Arm 5:Day 6 pre-dose and at multiple time points(up to 264 hrs)post-dose;Arm 2, 3:Days 1,15 pre-dose and at multiple time points(up to 216 hrs)post-dose;Arm 4:Day 8 pre-dose and at multiple time points(up to 168 hrs)post-dose

Interventionhours (Median)
Arm 1: Ixazomib 2.5 mg1.090
Arm 1: Ixazomib 2.5 mg + Ketoconazole 400 mg1.500
Arm 2: Ixazomib 4 mg Capsule A1.290
Arm 2: Ixazomib 4 mg Capsule B1.250
Arm 3: Ixazomib 4 mg Fasted1.020
Arm 3: Ixazomib 4 mg Fed4.000
Arm 4: Ixazomib 4 mg + Rifampin 600 mg1.450
Arm 5: Ixazomib 2.5 mg + Clarithromycin 500 mg1

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Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

(NCT01454076)
Timeframe: Cycle 1 Day 1 up to 30 days after last dose of study drug (Arm 1 and 5: Cycle 19 Day 45; Arm 2: Cycle 7 Day 45; Arm 3: Cycle 22 Day 45; Arm 4: Cycle 25 Day 45)

,,,,
Interventionparticipants (Number)
TEAEsSAEs
Arm 1: Ixazomib 2.5 mg + Ketoconazole 400 mg2912
Arm 2: Ixazomib 4 mg Capsule A or B205
Arm 3: Ixazomib 4 mg Fasted or Fed2412
Arm 4: Ixazomib 4 mg + Rifampin 600 mg183
Arm 5: Ixazomib 2.5 mg + Clarithromycin 500 mg2110

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Percentage of Participants With Best Overall Response

Best overall response for a participant is best observed post-baseline disease response as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1: Complete response (CR) was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than (<) 10 millimeter [mm]). No new lesions. Partial response (PR) was defined as greater than or equal to (>=) 30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. Stable disease (SD) was defined as not qualifying for CR, PR, Progressive Disease (PD). An increase of >=20% from the nadir (or baseline, if it represents the point at which the sum of target disease was lowest) represents PD. (NCT01454076)
Timeframe: Baseline up to end of treatment (approximately 1.9 years)

,,,,
Interventionpercentage of participants (Number)
CRPRSDPD
Arm 1: Ixazomib 2.5 mg + Ketoconazole 400 mg006338
Arm 2: Ixazomib 4 mg Capsule A or B005050
Arm 3: Ixazomib 4 mg Fasted or Fed063559
Arm 4: Ixazomib 4 mg + Rifampin 600 mg005347
Arm 5: Ixazomib 2.5 mg + Clarithromycin 500 mg015347

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Number of Participants With Change From Baseline in Pain Response

"Pain response was defined as 30% reduction from Baseline in Brief Pain Inventory-Short Form (BPI-SF) worst pain score over the last 24 hours without an increase in analgesic (oral morphine equivalents) use at 2 consecutive evaluations. The BPI-SF contains 15 items designed to capture the pain severity (worst, least, average, and now [current pain]), pain location, medication to relieve the pain, and the interference of pain with various daily activities including general activity, mood, walking activity, normal work, relations with other people, sleep, and enjoyment of life. The pain severity items are rated on a 0 to 10 scale where: 0=no pain and 10=pain as bad as you can imagine and averaged for a total score of 0 (best) to 10 (Worst)." (NCT01564537)
Timeframe: Baseline and end of treatment (EOT) (up to approximately 38 months)

,
InterventionParticipants (Count of Participants)
BaselineEOT
Ixazomib+ Lenalidomide + Dexamethasone345145
Placebo + Lenalidomide + Dexamethasone351153

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Plasma Concentration Over Time for Ixazomib

(NCT01564537)
Timeframe: Pre-dose and post-dose at multiple timepoints up to Cycle 10 Day 1 (each cycle length = 28 days)

Interventionμg/mL (Mean)
Cycle 1 Day 1, 1 Hour Post-DoseCycle 1 Day 1, 4 Hours Post-DoseCycle 1 Day 14, Pre-DoseCycle 2 Day 1, Pre-DoseCycle 2 Day 14, Pre-DoseCycle 3 Day 1, Pre-DoseCycle 4 Day 1, Pre-DoseCycle 5 Day 1, Pre-DoseCycle 6 Day 1, Pre-DoseCycle 7 Day 1, Pre-DoseCycle 8 Day 1, Pre-DoseCycle 9 Day 1, Pre-DoseCycle 10 Day 1, Pre-Dose
Placebo + Lenalidomide + Dexamethasone0000000000000

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Plasma Concentration Over Time for Ixazomib

(NCT01564537)
Timeframe: Pre-dose and post-dose at multiple timepoints up to Cycle 10 Day 1 (each cycle length = 28 days)

Interventionμg/mL (Mean)
Cycle 1 Day 1Cycle 1 Day 1, 1 Hour Post-DoseCycle 1 Day 1, 4 Hours Post-DoseCycle 1 Day 14, Pre-DoseCycle 2 Day 1, Pre-DoseCycle 2 Day 14, Pre-DoseCycle 3 Day 1, Pre-DoseCycle 4 Day 1, Pre-DoseCycle 5 Day 1, Pre-DoseCycle 6 Day 1, Pre-DoseCycle 7 Day 1, Pre-DoseCycle 8 Day 1, Pre-DoseCycle 9 Day 1, Pre-DoseCycle 10 Day 1, Pre-Dose
Ixazomib+ Lenalidomide + Dexamethasone4.7936.315.66.832.47.122.482.412.422.572.712.372.512.82

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Duration of Response (DOR)

DOR was measured as the time in months from the date of first documentation of a confirmed response of PR or better (CR [including sCR] + PR+ VGPR) to the date of the first documented disease progression (PD) among participants who responded to the treatment. Response was assessed by the investigator using International Myeloma Working Group (IMWG) Criteria. (NCT01564537)
Timeframe: Day 1 of each cycle (every 4 weeks) until disease progression up to approximately 38 months

Interventionmonths (Median)
Ixazomib+ Lenalidomide + Dexamethasone26.0
Placebo + Lenalidomide + Dexamethasone21.7

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OS in High-Risk Participants

Overall survival (OS) is defined as the time from the date of randomization to the date of death. High-risk participants are defined as participants carrying cytogenic abnormalities: del(17), translocation t(4;14), or t(14;16) as reported by the central laboratory combined with those cases that lacked a central laboratory result but with known del (17), t(4;14), or t(14;16) by local laboratory. Cytogenetic abnormalities of del(13) and +1q are not included in the analysis. Participants without documentation of death at the time of the analysis were censored at the date when they were last known to be alive. Data is only reported for high-risk participants. (NCT01564537)
Timeframe: From the time of screening until disease progression and thereafter every 12 weeks until death or study termination (up to approximately 97 months)

Interventionmonths (Median)
Ixazomib+ Lenalidomide + Dexamethasone46.9
Placebo + Lenalidomide + Dexamethasone30.9

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Overall Response Rate (ORR) as Assessed by the IRC

ORR was defined as the percentage of participants with Complete Response (CR) including stringent complete response (sCR), very good partial response (VGPR) and Partial Response (PR) assessed by the IRC using IMWG criteria. Percentages are rounded off to single decimal. (NCT01564537)
Timeframe: Day 1 of each cycle (every 4 weeks) until disease progression up to approximately 27 months(approximate median follow-up 15 months)

Interventionpercentage of participants (Number)
Ixazomib+ Lenalidomide + Dexamethasone78.3
Placebo + Lenalidomide + Dexamethasone71.5

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Overall Response Rate in Participants Defined by Polymorphism

Data is reported for percentage of participants defined by polymorphism defined by polymorphisms in proteasome genes, such as polymorphism P11A in PSMB1 gene. Percentages are rounded off to single decimal. (NCT01564537)
Timeframe: Day 1 of each cycle (every 4 weeks) until disease progression up to approximately 27 months (approximate median follow-up 15 months)

Interventionpercentage of participants (Number)
Ixazomib+ Lenalidomide + Dexamethasone80.3
Placebo + Lenalidomide + Dexamethasone75.7

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Overall Survival (OS)

Overall survival is defined as the time from the date of randomization to the date of death. Participants without documentation of death at the time of the analysis were censored at the date when they were last known to be alive. (NCT01564537)
Timeframe: From date of randomization until death (up to approximately 97 months)

Interventionmonths (Median)
Ixazomib+ Lenalidomide + Dexamethasone53.6
Placebo + Lenalidomide + Dexamethasone51.6

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Overall Survival in High-Risk Participants Carrying Deletion 17 [Del(17)]

Overall survival is defined as the time from the date of randomization to the date of death. The high-risk participants whose myeloma carried del(17) subgroup was defined as the cases reported as positive for del(17) by the central laboratory combined with those cases that lacked a central laboratory result but with known del (17) by local laboratory. Participants without documentation of death at the time of the analysis were censored at the date when they were last known to be alive. Data is only reported high-risk participants with Del(17). (NCT01564537)
Timeframe: From the time of screening until disease progression and thereafter every 12 weeks until death or study termination (up to approximately 97 months)

Interventionmonths (Median)
Ixazomib+ Lenalidomide + Dexamethasone42.2
Placebo + Lenalidomide + Dexamethasone29.4

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Percentage of Participants With Complete Response (CR) and Very Good Partial Response (VGPR) as Assessed by the IRC

Response was assessed by the IRC using International Myeloma Working Group (IMWG) Criteria. CR is defined as negative immunofixation on the serum and urine and; disappearance of any soft tissue plasmacytomas and; < 5% plasma cells in bone marrow. VGPR is defined as Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hours. Percentages are rounded off to single decimal. (NCT01564537)
Timeframe: Day 1 of each cycle (every 4 weeks) until disease progression up to approximately 27 months (approximate median follow-up 15 months)

Interventionpercentage of participants (Number)
Ixazomib + Lenalidomide + Dexamethasone48.1
Placebo + Lenalidomide + Dexamethasone39.0

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PFS in High-Risk Participants

Progression Free Survival (PFS) is defined as the time from the date of randomization to the date of first documentation of disease progression or death due to any cause, whichever occurs first. Response was assessed by independent review committee (IRC) using IMWG response criteria. High-risk participants are defined as participants carrying cytogenic abnormalities: del(17), translocation t(4;14), or t(14;16) as reported by the central laboratory combined with those cases that lacked a central laboratory result but with known del (17), t(4;14), or t(14;16) by local laboratory. Cytogenetic abnormalities of del(13) and +1q are not included in the analysis. (NCT01564537)
Timeframe: From date of randomization until disease progression or death up to approximately 38 months (approximate median follow-up 15 months)

Interventionmonths (Median)
Ixazomib+ Lenalidomide + Dexamethasone18.7
Placebo + Lenalidomide + Dexamethasone9.3

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Progression Free Survival (PFS) as Assessed by the Independent Review Committee (IRC)

Progression Free Survival (PFS) is defined as the time from the date of randomization to the date of first documentation of disease progression (PD) or death due to any cause, whichever occurs first. Response including PD was assessed by independent review committee (IRC) using the International Myeloma Working Group (IMWG) response criteria. PD requires 1 of the following: Increase of ≥ 25% from nadir in: Serum M-component (absolute increase ≥ 0.5 g/dl); Urine M-component (absolute increase ≥ 200 mg/24 hours); In patients without measurable serum and urine M-protein levels the difference between involved and uninvolved free light chain (FLC) levels (absolute increase > 10 mg/dl); Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium > 11.5 mg/dl) attributed solely to plasma cell proliferative disease. Status evaluated every 4 weeks until disease progression (PD) was confirmed. (NCT01564537)
Timeframe: From date of randomization until disease progression or death up to approximately 27 months (approximate median follow-up 15 months)

Interventionmonths (Median)
Ixazomib+ Lenalidomide + Dexamethasone20.6
Placebo + Lenalidomide + Dexamethasone14.7

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Time to Progression (TTP) as Assessed by the IRC

TTP was measured as the time in months from the first dose of study treatment to the date of the first documented progressive disease (PD) as assessed by the IRC using IMWG criteria. (NCT01564537)
Timeframe: Day 1 of each cycle (every 4 weeks) until disease progression up to approximately 27 months (approximate median follow-up 15 months)

Interventionmonths (Median)
Ixazomib+ Lenalidomide + Dexamethasone22.4
Placebo + Lenalidomide + Dexamethasone17.6

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Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) Questionnaire (EORTC-QLQ-C30)

The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer participants. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact).The EORTC-QLQ-C30 Global Health Status/QOL Scale is scored between 0 and 100, where higher scores indicate better Global Health Status/QOL. Negative changes from baseline indicate deterioration in QOL or functioning and positive changes indicate improvement. Scores are linearly transformed to a 0-100 scale. High scores for the global and functional domains indicate higher quality of life or functioning. Higher scores on the symptom scales represent higher levels of symptomatology or problems. (NCT01564537)
Timeframe: Baseline, EOT and follow-up (up to approximately 97 months)

Interventionscore on a scale (Mean)
Global Health Index: BaselineGlobal Health Index: End of TreatmentPhysical Functioning: BaselinePhysical Functioning: EOTRole Functioning: BaselineRole Functioning: EOTEmotional Functioning: BaselineEmotional Functioning: EOTCognitive Functioning: BaselineCognitive Functioning: EOTSocial Functioning: BaselineSocial Functioning: EOTFatigue: BaselineFatigue: EOTPain: BaselinePain: EOTNausea and Vomiting: BaselineNausea and Vomiting: EOTDyspnea: BaselineDyspnea: EOTInsomnia: BaselineInsomnia: EOTAppetite Loss: BaselineAppetite Loss: EOTConstipation: BaselineConstipation: EOTDiarrhea: BaselineDiarrhea: EOTFinancial Difficulties: BaselineFinancial Difficulties: EOT
Ixazomib+ Lenalidomide + Dexamethasone58.4-6.070.0-4.768.4-8.675.1-2.181.9-7.677.9-6.938.46.038.02.75.03.421.25.727.40.916.94.712.2-1.36.317.216.70.5

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Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) Questionnaire (EORTC-QLQ-C30)

The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer participants. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact).The EORTC-QLQ-C30 Global Health Status/QOL Scale is scored between 0 and 100, where higher scores indicate better Global Health Status/QOL. Negative changes from baseline indicate deterioration in QOL or functioning and positive changes indicate improvement. Scores are linearly transformed to a 0-100 scale. High scores for the global and functional domains indicate higher quality of life or functioning. Higher scores on the symptom scales represent higher levels of symptomatology or problems. (NCT01564537)
Timeframe: Baseline, EOT and follow-up (up to approximately 97 months)

Interventionscore on a scale (Mean)
Global Health Index: BaselineGlobal Health Index: End of TreatmentGlobal Health Index: Last Follow-upPhysical Functioning: BaselinePhysical Functioning: EOTPhysical Functioning: Last Follow-upRole Functioning: BaselineRole Functioning: EOTRole Functioning: Last Follow-upEmotional Functioning: BaselineEmotional Functioning: EOTEmotional Functioning: Last Follow-upCognitive Functioning: BaselineCognitive Functioning: EOTCognitive Functioning: Last Follow-upSocial Functioning: BaselineSocial Functioning: EOTSocial Functioning: Last Follow-upFatigue: BaselineFatigue: EOTFatigue: Last Follow-upPain: BaselinePain: EOTPain: Last Follow-upNausea and Vomiting: BaselineNausea and Vomiting: EOTNausea and Vomiting: Last Follow-upDyspnea: BaselineDyspnea: EOTDyspnea: Last Follow-upInsomnia: BaselineInsomnia: EOTInsomnia: Last Follow-upAppetite Loss: BaselineAppetite Loss: EOTAppetite Loss: Last Follow-upConstipation: BaselineConstipation: EOTConstipation: Last Follow-upDiarrhea: BaselineDiarrhea: EOTDiarrhea: Last Follow-upFinancial Difficulties: BaselineFinancial Difficulties: EOTFinancial Difficulties: Last Follow-up
Placebo + Lenalidomide + Dexamethasone56.4-6.016.767.3-6.20.064.4-8.6-16.775.3-6.1-25.081.6-5.8-50.075.3-7.90.039.56.722.238.53.80.06.00.633.323.72.30.030.5-0.533.315.36.50.013.52.233.38.110.80.018.61.3-33.3

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Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Multiple Myeloma Module (QLQ-MY-20)

The EORTC-QLQ-MY-20 is a patient-completed, 20-question quality of life questionnaire that has 4 independent subscales, 2 functional subscales (body image, future perspective), and 2 symptoms scales (disease symptoms and side-effects of treatment). The participant answers questions about their health during the past week using a 4-point scale where 1=Not at All to 4=Very Much. A negative change from Baseline indicates improvement. Scores are linearly transformed to a 0-100 scale. Higher scores on the symptom scales (e.g. Disease Symptoms, Side Effects of Treatment) represent higher levels of symptomatology or problems. High scores for Body Image and Future Perspective represent better quality of life or functioning. (NCT01564537)
Timeframe: Baseline, EOT and follow-up (up to approximately 97 months)

Interventionscore on a scale (Mean)
Disease Symptoms: BaselineDisease Symptoms: EOTSide Effects of Treatment: BaselineSide Effects of Treatment: EOTSide Effects of Treatment: Last Follow-upBody Image: BaselineBody Image: EOTBody Image: Last Follow-upFuture Perspective: BaselineFuture Perspective: EOTFuture Perspective: Last Follow-up
Placebo + Lenalidomide + Dexamethasone30.41-2.5817.974.4337.0479.48-5.38-33.360.26-2.75-11.11

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Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Multiple Myeloma Module (QLQ-MY-20)

The EORTC-QLQ-MY-20 is a patient-completed, 20-question quality of life questionnaire that has 4 independent subscales, 2 functional subscales (body image, future perspective), and 2 symptoms scales (disease symptoms and side-effects of treatment). The participant answers questions about their health during the past week using a 4-point scale where 1=Not at All to 4=Very Much. A negative change from Baseline indicates improvement. Scores are linearly transformed to a 0-100 scale. Higher scores on the symptom scales (e.g. Disease Symptoms, Side Effects of Treatment) represent higher levels of symptomatology or problems. High scores for Body Image and Future Perspective represent better quality of life or functioning. (NCT01564537)
Timeframe: Baseline, EOT and follow-up (up to approximately 97 months)

Interventionscore on a scale (Mean)
Disease Symptoms: BaselineDisease Symptoms: EOTDisease Symptoms: Last Follow-upSide Effects of Treatment: BaselineSide Effects of Treatment: EOTBody Image: BaselineBody Image: EOTFuture Perspective: BaselineFuture Perspective: EOT
Ixazomib+ Lenalidomide + Dexamethasone29.71-2.351.1117.234.5278.00-0.2756.992.76

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Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Eastern Cooperative Oncology Group (ECOG) performance score, laboratory values, vital sign measurements and reported adverse events (AEs) were collected and assessed to evaluate the safety of therapy throughout the study. An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event. (NCT01564537)
Timeframe: From the date of signing of the informed consent form through 30 days after the last dose of study drug up to approximately 115 months

,
InterventionParticipants (Count of Participants)
TEAEsSAEs
Ixazomib+ Lenalidomide + Dexamethasone359205
Placebo + Lenalidomide + Dexamethasone357201

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Cmax: Maximum Observed Plasma Concentration for Ixazomib

(NCT01645930)
Timeframe: Cycle 1, Day 15 pre-dose and multiple time-points (up to 336 hours) post-dose

Interventionng/mL (Mean)
Ixazomib+Lenalidomide+Dexamethasone57.57

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Duration of Response (DOR)

DOR was defined as the length of time between the date of first documented response (PR, VGPR, or CR) and the date of first documented progressive disease (PD). According to IMWG criteria: CR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in bone marrow; PR: ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg per 24 hours. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein plus urine M-protein level <100 mg per 24 hour. (NCT01645930)
Timeframe: From date of documentation of a confirmed response to date of progressive disease, (approximately 20 months)

Interventionmonths (Median)
Ixazomib+Lenalidomide+Dexamethasone12.9

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Number of Participants With Dose Limiting Toxicities (DLTs)

DLT was defined as any of the following AEs that were considered by investigator to be possibly related to therapy: 1. Grade 4 neutropenia lasting at least 7 consecutive days; 2. Grade 3 neutropenia with fever and/or infection; 3. Grade 4 thrombocytopenia at least 7 consecutive days; 4. Grade 3 thrombocytopenia with clinically significant bleeding; 5. Platelet count <10,000/mm^3; 6. Grade 2 peripheral neuropathy with pain or ≥Grade 3 peripheral neuropathy; 7. Grade 3 or greater nausea and / or emesis despite the use of optimal anti-emetic prophylaxis; 8. Grade 3 or greater diarrhea that occurred despite maximal supportive therapy; 9. Any other Grade 3 or greater nonhematologic toxicity with the following exceptions: Grade 3 arthralgia/myalgia, <1 week Grade 3 fatigue; 10. A delay of >2 weeks in the subsequent cycle of treatment; 11. Other combination study drug-related nonhematologic toxicities ≥Grade 2 that, in the opinion of the investigator, required discontinuation of study drug. (NCT01645930)
Timeframe: Cycle 1 (up to Day 28)

Interventionparticipants (Number)
Ixazomib+Lenalidomide+Dexamethasone2

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Percentage of Participants With Confirmed Best Response Category

Percentage of participants who achieve or maintain any best response category during the treatment period were reported. Best response includes complete response (CR), very good partial response (VGPR), and partial response (PR). Response was assessed according to IMWG criteria. CR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in bone marrow; PR: ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg per 24 hours. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein plus urine M-protein level <100 mg per 24 hour. (NCT01645930)
Timeframe: From Cycle 1, Day 1 to Cycle 3, Day 1 until disease progression (approximately 20 months)

Interventionpercentage of participants (Number)
Ixazomib+Lenalidomide+Dexamethasone53.5

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Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib

(NCT01645930)
Timeframe: Cycle 1, Day 1 pre-dose and multiple time-points (up to 168 hours) post-dose

Interventionhours (Median)
Ixazomib+Lenalidomide+Dexamethasone1.5

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Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib

(NCT01645930)
Timeframe: Cycle 1, Day 15 pre-dose and multiple time-points (up to 336 hours) post-dose

Interventionhours (Median)
Ixazomib+Lenalidomide+Dexamethasone2.0

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Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A SAE is defined as any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or was a medically important event. (NCT01645930)
Timeframe: From the first dose of study drug through 30 days after the last dose of study drug (up to 577 days)

Interventionparticipants (Number)
AEsSAEs
Ixazomib+Lenalidomide+Dexamethasone4318

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Number of Participants With Clinically Significant Laboratory Abnormalities Reported as Adverse Events of ≥Grade 3 Intensity

Clinically significant laboratory abnormalities were defined as any test results which were observed beyond the clinically acceptable limits as per the discretion of investigator. Clinical laboratory tests included chemistry, hematology and urinalysis tests. (NCT01645930)
Timeframe: From the first dose of study drug through 30 days after the last dose of study drug (up to 577 days)

Interventionparticipants (Number)
Alanine Aminotransferase IncreasedAspartate Aminotransferase IncreasedBlood Creatinine IncreasedHaemoglobin DecreasedNeutrophil Count DecreasedPlatelet Count DecreasedAnaemiaFebrile NeutropeniaNeutropeniaThrombocytopeniaHyperglycaemiaHypocalcaemiaHypokalaemiaHypomagnesaemiaHyponatraemiaHypophosphataemia
Ixazomib+Lenalidomide+Dexamethasone21112461128135112

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Number of Participants With Clinically Significant Vital Signs Reported as Adverse Events

The number of participants who meet markedly abnormal criteria for vital signs, included diastolic and systolic blood pressure, heart rate, oral temperature, respiratory rate, and body weight. (NCT01645930)
Timeframe: From the first dose of study drug through 30 days after the last dose of study drug (up to 577 days)

Interventionparticipants (Number)
Grade 1 or 2 HypertensionGrade 2 Hypotension
Ixazomib+Lenalidomide+Dexamethasone41

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AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for Ixazomib

(NCT01645930)
Timeframe: Cycle 1, Day 1 pre-dose and multiple time-points (up to 168 hours) post-dose

Interventionhr*ng/mL (Mean)
Ixazomib+Lenalidomide+Dexamethasone685.9

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AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for Ixazomib

(NCT01645930)
Timeframe: Cycle 1, Day 15 pre-dose and multiple time-points (up to 336 hours) post-dose

Interventionhr*ng/mL (Mean)
Ixazomib+Lenalidomide+Dexamethasone1746.0

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Cmax: Maximum Observed Plasma Concentration for Ixazomib

(NCT01645930)
Timeframe: Cycle 1, Day 1 pre-dose and multiple time-points (up to 168 hours) post-dose

Interventionng/mL (Mean)
Ixazomib+Lenalidomide+Dexamethasone37.57

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Change From Baseline in SF-36 Physical Component Summary Score at Week 28 of the PFS Follow-up

SF-36 Version 2 is a multipurpose, participant completed, short-form health survey with 36 questions that consists of an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures. Physical component summary (PCS) is mostly contributed by physical function (PF), role physical (RP), bodily pain (BP), and general health (GH). Mental component summary (MCS) is mostly contributed by mental health (MH), role emotional (RE), social function (SF), and vitality (VT). Each component on the SF-36 item health survey is scored from 0 (best) to 100 (worst). Total score ranges from 0-100, where higher scores are associated with less disability and better quality of life. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure. (NCT01659658)
Timeframe: Baseline, Week 28 of the PFS Follow-up

Interventionscore on a scale (Mean)
Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide10.3

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Duration of Hematologic Response

Duration of hematologic response (DOR) was defined as the time from the date of first documentation of a hematologic response to the date of first documented hematologic disease progression as determined by the investigator. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure. (NCT01659658)
Timeframe: From time of first documented response to disease progression (up to 115 months)

Interventionmonths (Median)
Arm A: Ixazomib + DexamethasoneNA
Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide21.19

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EuroQol 5-Dimension 3-Level (EQ-5D-3L) Visual Analogue Scale Score

The EQ visual analogue scale (VAS) records the participant's self-rated health on a 20 centimeter vertical VAS that ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). Baseline is defined as the value collected at the time closest to, but prior to, the start of study drug administration. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure. (NCT01659658)
Timeframe: At Week 28 of the OS follow-up

Interventionscore on a scale (Mean)
Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide23.0

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Hematologic Disease Progression Free Survival

Hematologic disease PFS was defined as the time from the date of randomization to the date of first documentation of hematologic PD according to central laboratory results and ISA criteria as evaluated by an adjudication committee, or death due to any cause, whichever occurred first. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure. (NCT01659658)
Timeframe: From first dose of study drug until discontinuation of study drug due to disease progression or unacceptable toxicity, or death whichever occurs first (up to 115 months)

Interventionmonths (Median)
Arm A: Ixazomib + Dexamethasone29.50
Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide27.73

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Number of Hospitalizations

A hospitalization was defined as at least one overnight stay in an intensive care unit and/or non-intensive care unit. If a single hospitalization included both an intensive care unit stay and a non-intensive care unit stay, the hospitalization was counted only once (as an intensive care unit stay). The mean number of hospitalizations is reported in this outcome measure. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure. (NCT01659658)
Timeframe: From first dose of study drug until discontinuation of study drug due to disease progression or unacceptable toxicity, or death whichever occurs first (up to 115 months)

Interventionhospitalizations (Mean)
Arm A: Ixazomib + Dexamethasone1.8
Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide1.4

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Change From Baseline in 36-item Short Form General Health Survey (SF-36) Mental Component Summary Score at Week 28 of the PFS Follow-up

SF-36 Version 2 is a multipurpose, participant completed, short-form health survey with 36 questions that consists of an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures. Physical component summary (PCS) is mostly contributed by physical function (PF), role physical (RP), bodily pain (BP), and general health (GH). Mental component summary (MCS) is mostly contributed by mental health (MH), role emotional (RE), social function (SF), and vitality (VT). Each component on the SF-36 item health survey is scored from 0 (best) to 100 (worst). Total score ranges from 0-100, where higher scores are associated with less disability and better quality of life. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure. (NCT01659658)
Timeframe: Baseline, Week 28 of the PFS Follow-up

Interventionscore on a scale (Mean)
Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide2.0

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2-Year Vital Organ (Heart or Kidney) Deterioration and Mortality Rate

Cardiac (Heart) deterioration was defined as the need for hospitalization for heart failure. Kidney deterioration was defined as progression to end-stage renal disease (ESRD) with the need for maintenance dialysis or renal transplantation. Vital organ deterioration was evaluated by an adjudication committee. Percentages were rounded off to the nearest decimal. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure. (NCT01659658)
Timeframe: Up to 2 years

Interventionpercentage of participants (Number)
Arm A: Ixazomib + Dexamethasone47
Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide54

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Plasma Concentration of Ixazomib

As prespecified in the protocol, data for this outcome measure was planned to be collected for ixazomib arm group only. (NCT01659658)
Timeframe: Cycle 1, Day 1: 1, 4 hours postdose, Day 14: 144 hours postdose; Cycle 2, Day 1: predose, Day 14: 144 hours postdose; Cycles 3 to 10, Day 1: predose (cycle length=28 days)

Interventionnanogram per milliliter (ng/mL) (Geometric Mean)
Cycle 1 Day 1: 1 Hour Post-doseCycle 1 Day 14: 4 Hours Post-doseCycle 1 Day 14: 144 Hours Post-doseCycle 2 Day 1: Pre-doseCycle 2 Day 14: 144 Hours Post-doseCycle 3 Day 1: Pre-doseCycle 4 Day 1 Pre-doseCycle 5 Day 1 Pre-doseCycle 6 Day 1: Pre-doseCycle 7 Day 1: Pre-doseCycle 8 Day 1: Pre-doseCycle 9 Day 1: Pre-doseCycle 10 Day 1: Pre-dose
Arm A: Ixazomib + Dexamethasone16.51810.6523.8752.0004.7262.1872.2762.2642.2352.2992.0382.1432.232

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Vital Organ Progression Free Survival

Vital organ PFS is defined as the time from the date of randomization to the date of first documentation of progression of vital organ (heart or kidney) according to central laboratory results and ISA criteria as evaluated by an adjudication committee, or death due to any cause, whichever occurs first. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure. (NCT01659658)
Timeframe: From first dose of study drug until discontinuation of study drug due to disease progression or unacceptable toxicity, or death whichever occurs first (up to 115 months)

Interventionmonths (Median)
Arm A: Ixazomib + Dexamethasone15.77
Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide11.01

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Number of Participants in Each Category of the EuroQol 5-Dimensional (EQ-5D) Questionnaire Score

The European Quality of Life (EuroQOL) 5-Dimensional (EQ-5D) is a patient completed questionnaire consisting of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). Each dimension has 3 possible choices: no problems to extreme problems. Higher scores=worsening of the quality of life. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure. (NCT01659658)
Timeframe: At Week 28 of the OS follow-up

,
InterventionParticipants (Count of Participants)
Mobility: No Problems in Walking AboutMobility: Some Problem in Walking AboutMobility: Confined to BedSelf-Care: No Problems With Self- CareSelf-Care: Some Problems Washing or DressingSelf-Care: Unable to Wash or DressUsual Activities: No Problems With Performing Usual ActivitiesUsual Activities: Some Problem With Performing Usual ActivitiesUsual Activities: Unable to Performing Usual ActivitiesPain/Discomfort: No Pain or DiscomfortPain/Discomfort: Moderate Pain or DiscomfortPain/Discomfort: Extreme Pain or DiscomfortAnxiety/Depression: Not Anxious or DepressedAnxiety/Depression: Moderately Anxious or DepressedAnxiety/Depression: Extremely Anxious or Depressed
Arm A: Ixazomib + Dexamethasone000000000000000
Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide010010010010001

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Time to Vital Organ (Heart or Kidney) Deterioration and Mortality Rate

Time to vital organ deterioration or death was assessed by the investigator and defined as the time from randomization to vital organ (heart or kidney) deterioration or death, whichever occurs first. Cardiac deterioration is defined as the need for hospitalization for heart failure. Kidney deterioration is defined as progression to ESRD with the need for maintenance dialysis or renal transplantation. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure. (NCT01659658)
Timeframe: From randomization to time of vital organ deterioration or death (up to 115 months)

Interventionmonths (Median)
Arm A: Ixazomib + Dexamethasone38.67
Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide26.09

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Time To Treatment Failure (TTF)

TTF was defined as the time from randomization to the date of first documented treatment failure. Treatment failure was defined as: 1) death due to any cause; 2) hematologic progression or major organ progression according to central laboratory results and ISA criteria as evaluated by the investigator; 3) clinically morbid organ disease requiring additional therapy; or 4) withdrawn for any reason. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure. (NCT01659658)
Timeframe: From first dose of study drug until discontinuation of study drug due to disease progression or unacceptable toxicity, or death whichever occurs first (up to 115 months)

Interventionmonths (Median)
Arm A: Ixazomib + Dexamethasone10.32
Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide5.32

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Time To Subsequent Anticancer Treatment

Time to subsequent anticancer therapy was defined as the time from randomization to the first date of subsequent anticancer therapy. Participants without subsequent anticancer therapy were censored at the date of death or last known to be alive. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure. (NCT01659658)
Timeframe: From first dose of study drug until subsequent anticancer treatment (up to 115 months)

Interventionmonths (Median)
Arm A: Ixazomib + Dexamethasone26.48
Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide12.45

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Progression Free Survival (PFS)

PFS was defined as the time from the date of randomization to the date of first documentation of hematologic disease progression, or organ (cardiac or renal) progression, or death due to any cause, whichever occurred first according to central laboratory results and ISA criteria as evaluated by the investigator. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure. (NCT01659658)
Timeframe: From first dose of study drug until discontinuation of study drug due to disease progression or unacceptable toxicity, or death whichever occurs first (up to 115 months)

Interventionmonths (Median)
Arm A: Ixazomib + Dexamethasone11.86
Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide7.62

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Percentage of Participants With Overall Hematologic Response

Overall hematologic response was defined as the percentage of participants with complete response (CR), very good partial response (VGPR) and partial response (PR) based on central laboratory results and the 2010 International Society of Amyloidosis (ISA) Consensus Criteria as assessed by an adjudication committee. CR: Complete disappearance of M-protein from serum and urine on immunofixation, and normalization of free light chain (FLC) ratio. VGPR: differential free light chain (difference between involved and uninvolved FLC levels; dFLC) < 40 mg/L. PR: ≥50% reduction in dFLC. Percentages were rounded off to the nearest decimal. (NCT01659658)
Timeframe: From first dose of study drug until discontinuation of study drug due to disease progression or unacceptable toxicity, or death whichever occurs first (up to 115 months)

Interventionpercentage of participants (Number)
Arm A: Ixazomib + Dexamethasone53
Arm B: Dexamethasone + Melphalan58
Arm B: Dexamethasone + Cyclophosphamide30
Arm B: Dexamethasone + Thalidomide50
Arm B: Dexamethasone + Lenalidomide51

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Percentage of Participants With Complete Hematologic Response

Complete hematologic response was defined as the percentage of participants with CR based on central laboratory results and the 2010 ISA Consensus Criteria as assessed by the investigator. CR: Complete disappearance of M-protein from serum and urine on immunofixation, and normalization of FLC ratio. Percentages were rounded off to the nearest decimal. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure. (NCT01659658)
Timeframe: From first dose of study drug until discontinuation of study drug due to disease progression or unacceptable toxicity, or death whichever occurs first (up to 115 months)

Interventionpercentage of participants (Number)
Arm A: Ixazomib + Dexamethasone30
Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide17

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Percentage of Participants With Best Vital Organ (Cardiac and/or Kidney) Response

Vital organ (heart and kidney) response rate was defined as the percentage of participants who achieved vital organ response according to central laboratory results and ISA criteria as evaluated by an adjudication committee. A vital organ response was defined as response of 1 or 2 of the involved vital organs with no change from Baseline in the rest of involved vital organs. Percentages were rounded off to the nearest decimal. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure. (NCT01659658)
Timeframe: From first dose of study drug until discontinuation of study drug due to disease progression or unacceptable toxicity, or death whichever occurs first (up to 115 months)

Interventionpercentage of participants (Number)
Arm A: Ixazomib + Dexamethasone19
Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide12

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Overall Survival

Overall survival was defined as the time from the date of randomization to the date of death. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure. (NCT01659658)
Timeframe: From first dose of study drug until discontinuation of study drug due to disease progression or unacceptable toxicity, or death whichever occurs first (up to 115 months)

Interventionmonths (Median)
Arm A: Ixazomib + Dexamethasone69.55
Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide43.17

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Number of Participants With Serious Adverse Events (SAEs)

A SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of an existing hospitalization, resulted in persistent or significant disability or incapacity, was a congenital anomaly/birth defect or medically important event. (NCT01659658)
Timeframe: From first dose of study drug through 30 days after administration of the last dose of study drug (up to 115 months)

InterventionParticipants (Count of Participants)
Arm A: Ixazomib + Dexamethasone44
Arm B: Dexamethasone + Melphalan11
Arm B: Dexamethasone + Cyclophosphamide2
Arm B: Dexamethasone + Thalidomide0
Arm B: Dexamethasone + Lenalidomide17

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Change From Baseline in Amyloidosis Symptom Scale Total Score at Week 28 of the PFS Follow-up

The amyloidosis symptom scale questionnaire is a participant completed questionnaire that evaluates symptom severity of 3 symptoms: Swelling, Shortness of Breath and Dizziness, each rated on an 11-point scale where: 0=no symptoms to 10=very severe symptoms. Higher scores indicate worsening of symptoms. Total Score is the sum of all responses from the amyloidosis symptom scale ranging from 0 to 30. Higher scores represent higher levels of symptomatology or problems and a negative change from baseline indicates improvement. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure. (NCT01659658)
Timeframe: Baseline, Week 28 of the PFS Follow-up

Interventionscore on a scale (Mean)
Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide-16.0

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Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) Score at Week 28 of the PFS Follow-up

The FACT/GOG-Ntx is a participant completed questionnaire that comprises 11 individual items evaluating symptoms of neurotoxicity on a 5-point scale where: 0=not at all (best) to 4=very much for a total possible score of 0 to 44. Symptom scores are inverted so that higher scores of FACT/GOG-Ntx indicate higher quality of life or functioning. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure. (NCT01659658)
Timeframe: Baseline, Week 28 of the PFS Follow-up

Interventionscore on a scale (Mean)
Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide0.0

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Number of Participants With Adverse Events

Adverse Event is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. (NCT01830816)
Timeframe: From signing of first dose of study drug up to the 30 days after the last dose of study drug (approximately up to 885 days)

Interventionparticipants (Number)
Normal Renal Function: Ixazomib19
Severe Renal Impairment: Ixazomib14
End-stage Renal Disease: Ixazomib6

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Unbound Cmax: Unbound Maximum Observed Plasma Concentration for Ixazomib

(NCT01830816)
Timeframe: Part A, Day 1: Predose and at multiple timepoints (up to 336 hours) post-dose

Interventionng/mL (Geometric Mean)
Normal Renal Function: Ixazomib0.300
Severe Renal Impairment: Ixazomib0.478
End-stage Renal Disease: Ixazomib0.213

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Unbound AUClast: Unbound Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ixazomib

(NCT01830816)
Timeframe: Part A, Day 1: Predose and at multiple timepoints (up to 336 hours) post-dose

Interventionhr*ng/mL (Geometric Mean)
Normal Renal Function: Ixazomib6.637
Severe Renal Impairment: Ixazomib9.249
End-stage Renal Disease: Ixazomib8.925

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Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib

(NCT01830816)
Timeframe: Part A, Day 1: Predose and at multiple timepoints (up to 336 hours) post-dose

Interventionhours (Median)
Normal Renal Function: Ixazomib1.0400
Severe Renal Impairment: Ixazomib1.0000
End-stage Renal Disease: Ixazomib1.2500

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Percentage of Participants With Overall Response (OR) in Relapsed/Refractory Multiple Myeloma (RRMM) Participants

Overall response rate defined as percentage of relapsed/refractory multiple myeloma participants who achieved partial response (PR), complete response (CR) and very good partial response (VGPR) according to International Myeloma Working Group Criteria. PR=>50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by >90% or <200 mg/24 h. If serum and urine M-protein are unmeasurable, >50% decrease in difference between involved and uninvolved free light chain levels in place of M-protein criteria. If serum and urine M-protein and serum free light assay are not measurable, >50% reduction in plasma cells in place of M-protein, provided baseline bone marrow plasma cell >0%; CR=negative immunofixation on serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow; VGPR=serum and urine M-protein detectable by immunofixation but not on electrophoresis or > 90% reduction in serum M-protein plus urine M-protein level <100 mg/24 h. (NCT01830816)
Timeframe: Day 1 of every other cycle from cycle 1 (each cycle of 28 days) up to progression of disease (approximately up to 855 days)

Interventionpercentage of participants (Number)
Normal Renal Function: Ixazomib29
Severe Renal Impairment: Ixazomib18
End-stage Renal Disease: Ixazomib0

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Duration of Response (DOR) in RRMM Participants

DOR was defined as time from date of first documentation of a PR or better to date of first documentation of progressive disease (PD) for responders. Increase of >25% from lowest response value in any one or more of following: Serum M-component and/or (absolute increase must be >0.5 g/dL); Urine M-component and/or (the absolute increase must be >200 mg/24 h); difference between involved and uninvolved free light chain (FLC) levels and the absolute increase must be > 10 mg/dL; Bone marrow plasma cell percentage; absolute percentage must be > 5%; Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcaemia (corrected serum calcium > 11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder. Responders without PD were censored at the date of the last response assessment that was stable disease (SD) or better. (NCT01830816)
Timeframe: Day 1 of every other cycle from cycle 1 (each cycle of 28 days) up to progression of disease (approximately up to 855 days)

Interventiondays (Median)
Normal Renal Function: Ixazomib134
Severe Renal Impairment: Ixazomib225

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Pain Response Rate as Assessed by the Brief Pain Inventory- Short Form (BPI-SF) and Analgesic Use

Pain response rate was defined as percentage of participants with pain response. Pain response was defined as the occurrence of at least a 30% reduction from baseline in BPI-SF worst pain score over the last 24 hours without an increase in analgesic use for 2 consecutive measurements > 28 days apart, were reported. Brief Pain Inventory - Short Form (m-BPI-SF) is a participant rated 11-point Likert rating scale ranged from 0 (no pain) to 10 (worst pain imaginable). Percentages are rounded off to the nearest single decimal. (NCT01850524)
Timeframe: Up to approximately 9 years

Interventionpercentage of participants (Number)
Placebo + LenDex51.3
Ixazomib + LenDex50.5

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Overall Response Rate (ORR)

ORR was defined as the percentage of participants who achieved CR + partial response (PR) + very good partial response (VGPR) (including sCR) or better relative to the ITT population during treatment period. CR was defined as negative immunofixation of serum and urine along with the disappearance of any soft tissue plasmacytomas and <5 % PC's in bone marrow. PR was defined as ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% along with ≥50% reduction in the size of soft tissue plasmacytomas. VGPR was defined as ≥90% in serum M-component plus urine M-component <100 mg/24. sCR is defined as stringent complete response. Percentages are rounded off to nearest whole numbers. (NCT01850524)
Timeframe: Up to approximately 9 years

Interventionpercentage of participants (Number)
Placebo + LenDex80
Ixazomib + LenDex82

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OS in High-risk Population Carrying Del(17p), t(4;14), or t(14;16) Mutations

OS was defined as the time from the date of randomization to the date of death, as assessed in high-risk population carrying del(17p), t(4;14), or t(14;16) mutations. High risk category includes t(4;14), t(14;16), or del(17) abnormalities. (NCT01850524)
Timeframe: From the date of randomization to death due to any cause (Up to approximately 9 years)

Interventionmonths (Median)
Placebo + LenDex43.1
Ixazomib + LenDex39.0

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Duration of Response

Duration of response was measured as the time from the date of first documentation of PR or better to the date of first documented progression (PD) for responders, as measured by IMWG criteria. (NCT01850524)
Timeframe: Up to approximately 9 years

Interventionmonths (Median)
Placebo + LenDex37.5
Ixazomib + LenDex50.6

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Complete Response (CR) Rate

CR rate was defined as the percentage of participants who achieve CR assessed by an IRC relative to the intent-to-treat (ITT) population during the treatment period. Percentage of participants with CR, as assessed by IMWG disease assessment criteria were reported. CR was defined as negative immunofixation of serum and urine along with the disappearance of any soft tissue plasmacytomas and <5 % plasma cells (PC's) in bone marrow. (NCT01850524)
Timeframe: Up to approximately 9 years

Interventionpercentage of participants (Number)
Placebo + LenDex14
Ixazomib + LenDex26

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Percentage of Participants With MRD-Negative Status as Assessed by Flow Cytometry

The absence of minimal residual disease (MRD negativity) was tested in all participants who achieve a CR and maintained it until Cycle 18, using bone marrow aspirates. (NCT01850524)
Timeframe: Up to Cycle 18 (cycle length = 28 days)

Interventionpercentage of participants (Number)
Placebo + LenDex50
Ixazomib + LenDex59

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PFS in High-risk Population Carrying Del(17p), t(4;14), or t(14;16) Mutations

PFS was defined as the time from the date of randomization to the date of first documentation of progressive disease based on central laboratory results and IMWG criteria as evaluated by an independent review committee (IRC) or death due to any cause, whichever occurs first, as assessed in high-risk population carrying del(17p), t(4;14), or t(14;16) mutations. (NCT01850524)
Timeframe: Up to approximately 9 years

Interventionmonths (Median)
Placebo + LenDex17.5
Ixazomib + LenDex22.4

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Progression Free Survival (PFS)

PFS was defined as the time from the date of randomization to the date of first documentation of progressive disease (PD) or death due to any cause according to International Myeloma Working Group (IMWG) criteria whichever occurs first. PD required one of the following: Increase of >=25% from nadir in: Serum M-component and/or (the absolute increase must be >=0.5 g/dL); Urine M-component and/or (the absolute increase must be >=200 mg/24 hours); in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain (FLC) levels (absolute increase must be > 10 mg/dL); Bone marrow plasma cell percentage: the absolute % must be >10%; development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; hypercalcemia (corrected serum calcium > 11.5 mg/dL or 2.85 mmol/L). (NCT01850524)
Timeframe: Up to approximately 79 months

Interventionmonths (Median)
Placebo + LenDex21.8
Ixazomib + LenDex35.3

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Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

An AE was any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. An SAE is any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of present hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect or is a medically important event that may not be immediately life-threatening or result in death or hospitalization, but may jeopardize the participant or may require intervention to prevent one of other outcomes listed in definition above, or involves suspected transmission via a medicinal product of an infectious agent. (NCT01850524)
Timeframe: From the date of randomization through 30 days after the last dose of study drug up to end of study (up to approximately 9 years)

,,,
InterventionParticipants (Count of Participants)
TEAEsSAEs
Ixazomib + LenDex (Exposure ≥19 Cycles)191125
Ixazomib+ LenDex (Exposure Up to 18 Cycles)163119
Placebo + LenDex (Exposure ≥19 Cycles)189119
Placebo + LenDex (Exposure Up to 18 Cycles)160105

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Progression Free Survival (PFS)-2

PFS2 was defined as the time from the date of randomization to the date of documentation of disease progression on the subsequent line of anticancer therapy, as assessed by the investigator in accordance with IMWG criteria, or death due to any cause, whichever occurs first. (NCT01850524)
Timeframe: Up to approximately 9 years

Interventionmonths (Median)
Placebo + LenDex52.2
Ixazomib + LenDex63.2

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Time to Pain Progression

Time to pain progression was assessed as the time from randomization to the date of initial progression classification. Pain progression was defined as the occurrence of 1 of the following and confirmed by 2 consecutive evaluations (To qualify as progression, the participant must have a BPI-SF worst pain score > 4 during pain progression): 1) a ≥ 2 point and 30% increase from Baseline in BPI-SF worst pain score without an increase in analgesic use, or 2) a 25% or more increase in analgesic use from Baseline without a decrease in BPI-SF worst pain score from Baseline. Brief Pain Inventory - Short Form (m-BPI-SF) is a participant rated 11-point Likert rating scale ranged from 0 (no pain) to 10 (worst pain imaginable). (NCT01850524)
Timeframe: Up to approximately 9 years

Interventionmonths (Median)
Placebo + LenDex47.1
Ixazomib + LenDexNA

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Time to Progression (TTP)

Time to progression was defined as the time from randomization to the date of first documented disease progression. (NCT01850524)
Timeframe: Up to approximately 9 years

Interventionmonths (Median)
Placebo + LenDex26.8
Ixazomib + LenDex45.8

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Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs)

The laboratory values assessment included serum chemistry and hematology. The Serum chemistry assessment included blood urea nitrogen (BUN), creatinine, bilirubin (total), urate, lactate dehydrogenase, phosphate, albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glucose, sodium, potassium, calcium, chloride, carbon dioxide (CO2), magnesium, thyroid stimulating hormone (TSH). Hematology assessment included hemoglobin, hematocrit, platelet (count), leukocytes with differential neutrophils (ANC). Participants with abnormal serum chemistry laboratory values reported as TEAEs are reported. TEAEs were defined as events that occurred after administration of the first dose of any agent in the study drug regimen and through 30 days after the last dose of any agent in the study drug regimen. (NCT01850524)
Timeframe: From the date of randomization through 30 days after the last dose of study drug up to end of study (up to approximately 9 years)

,,,
InterventionParticipants (Count of Participants)
HypokalaemiaBlood creatinine increasedHypophosphataemiaHypomagnesaemiaHyponatraemiaHyperglycaemiaHypocalcaemiaHyperkalaemiaAlanine aminotransferase increasedIron deficiencyHypercalcaemiaCreatinine renal clearance decreasedHypoalbuminaemiaAspartate aminotransferase increasedHyperuricaemiaAnaemiaThrombocytopeniaNeutropeniaNeutrophil count decreasedPlatelet count decreasedLymphopeniaFebrile neutropeniaLeukopeniaInternational normalised ratio increasedPancytopeniaIron deficiency anaemiaWhite blood cell count decreasedLymphocyte count decreased
Ixazomib + LenDex (Exposure ≥19 Cycles)3916915764310754352582439181542242420
Ixazomib+ LenDex (Exposure Up to 18 Cycles)336961076711212025334155677643112
Placebo + LenDex (Exposure ≥19 Cycles)3312311816123421713152144813422401133
Placebo + LenDex (Exposure Up to 18 Cycles)1692874133126251257153611605312151

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Time to Response

Time to response was defined as the time from the date of randomization to the first documentation of PR or better, as measured by IMWG criteria. (NCT01850524)
Timeframe: Up to approximately 9 years

Interventionmonths (Median)
Placebo + LenDex1.87
Ixazomib + LenDex1.02

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Change From Baseline in HRQOL Measured by EORTC-QLQ-MY20 Scale

EORTC QLQ-MY20 was a validated questionnaire to assess the overall quality of life in participants with multiple myeloma. The scale has 20 questions. Subscale and individual items include future perspective items 18-20, body image item 17, disease symptoms items 1-6, side effects of treatment items 7-16. Raw scores are averaged, and transformed to 0-100 scale, where higher score is better quality of life. Positive change indicates improvement. (NCT01850524)
Timeframe: Baseline to approximately 9 years

,
Interventionscore on a scale (Mean)
Disease Symptoms: BaselineDisease Symptoms: End of TreatmentSide-Effects: BaselineSide-Effects: End of TreatmentBody Image: BaselineBody Image: End of TreatmentFuture Perspective: BaselineFuture Perspective: End of Treatment
Ixazomib + LenDex29.2-5.317.63.381.2-2.355.06.0
Placebo + LenDex30.3-3.118.01.781.7-7.857.34.4

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Cmax: Maximum Plasma Concentration for Ixazomib

(NCT01850524)
Timeframe: Cycle 1 Day 1: Post-dose at multiple timepoints up to 4 hours; Pre-dose at Cycle 1 Day 14, Cycles 2-3 Day 1 and Day 14, Cycles 4-11 Day 1 (Each cycle length = 28 days)

Interventionnanograms per milliliter (Mean)
Cycle 1 Day 1: 1 Hour Post-doseCycle 1 Day 1: 4 Hours Post-doseCycle 1 Day 14: Pre-doseCycle 2 Day 1: Pre-doseCycle 2 Day 14: Pre-doseCycle 3 Day 1: Pre-doseCycle 3 Day 14: Pre-doseCycle 4 Day 1: Pre-doseCycle 5 Day 1: Pre-doseCycle 6 Day 1: Pre-doseCycle 7 Day 1: Pre-doseCycle 8 Day 1: Pre-doseCycle 9 Day 1: Pre-doseCycle 10 Day 1: Pre-doseCycle 11 Day 1: Pre-doseCycle 12 Day 1: Pre-dose
Ixazomib44.74516.2537.8672.6648.5212.7638.4903.2843.5942.6032.5982.5392.5932.5362.6672.686

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Overall Survival (OS)

OS was defined as the time from the date of randomization to the date of death. Participants without documented death at the time of analysis are censored at the date last known to be alive. (NCT01850524)
Timeframe: From the date of randomization to death due to any cause (Up to approximately 9 years)

Interventionmonths (Median)
Placebo + LenDexNA
Ixazomib + LenDexNA

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Number of Participants With Shifts From Baseline to Worst Value in Eastern Cooperative Oncology Group (ECOG) Performance Score

Eastern Cooperative Oncology Group (ECOG) scale score ranged from 0 to 5, where 0 indicated normal activity and 5 indicated death. The data is reported for those categories where at least 1 participant had worst post-baseline value for each ECOG score. (NCT01850524)
Timeframe: Up to approximately 9 years

,
InterventionParticipants (Count of Participants)
Baseline Score 0, Post-Baseline Score 0Baseline Score 0, Post-Baseline Score 1Baseline Score 0, Post-Baseline Score 2Baseline Score 0, Post-Baseline Score 3Baseline Score 1, Post-Baseline Score 0Baseline Score 1, Post-Baseline Score 1Baseline Score 1, Post-Baseline Score 2Baseline Score 1, Post-Baseline Score 3Baseline Score 1, Post-Baseline Score 4Baseline Score 2, Post-Baseline Score 1Baseline Score 2, Post-Baseline Score 2Baseline Score 2, Post-Baseline Score 3Baseline Score 2, Post-Baseline Score 4
Ixazomib + LenDex2352231011045794835113
Placebo + LenDex235720219672186122872

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Maximum Tolerated (MTD) Dose of Cyclophosphamide (Phase I)

Will be defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least 1/3 of patients, as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. (NCT01864018)
Timeframe: At 28 days

Interventionmg/m² weekly (Number)
Treatment (Ixazomib Citrate, Cyclophosphamide, Dexamethasone)400

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Rate of Complete Response, Very Good Partial Response, or Partial Response (Phase II, Cohort B)

The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportion will be calculated. (NCT01864018)
Timeframe: Up to 48 weeks

Interventionpercentage of participants (Number)
Treatment (Ixazomib Citrate, Cyclophosphamide, Dexamethasone)63

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Progression-free Survival (PFS)

The distribution of PFS will be estimated using the method of Kaplan Meier. (NCT01864018)
Timeframe: Time from registration to the earliest date of documentation of disease progression or death due to any cause, assessed up to 5 years

Interventionmonths (Median)
Phase I/II, Cohort ANA
Phase II, Cohort BNA

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Maximum Tolerated (MTD) Dose of Cyclophosphamide With Ixazomib and Dexamethasone (Phase I)

Will be defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least 1/3 of patients, as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. (NCT01864018)
Timeframe: At 28 days

Interventionmg weekly (Number)
MTD of ixazomibMTD of dexamethasone
Treatment (Ixazomib Citrate, Cyclophosphamide, Dexamethasone)440

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Survival Time

The distribution of survival time will be estimated using the method of Kaplan-Meier. (NCT01864018)
Timeframe: Time from registration to death due to any cause, assessed up to 5 years

Interventionmonths (Median)
Phase I/II, Cohort ANA
Phase II, Cohort BNA

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Percentage of Patients With Complete Response or Very Good Partial Response (Phase II, Cohort A)

The percentage of successes will be estimated by the number of successes divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportion will be calculated. (NCT01864018)
Timeframe: Up to 48 weeks

Interventionpercentage of participants (Number)
Treatment (Ixazomib Citrate, Cyclophosphamide, Dexamethasone)35

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Optimal Dose of MLN9708

This measure will be the maximum tolerated dose (MTD) at which no more than 1 Dose Limiting Toxicity (DLT) is observed. The starting dose of MLN9708 will be 2.3 mg orally on days 1, 8 and 15. If no DLT is seen in the first 3 patients, the dose will be increased to 3 mg and then to 4 mg orally on days 1, 8 and 15 in a classic 3 +3 phase I design. We will not attempt to increase the dose beyond 4 mg orally which, if achieved with acceptable toxicity, would be accepted as the recommended phase 2 dose (RP2D). 0 of 3 DLTs would allow escalation to the next dose level. 1 of 3 DLTs will require expanding to six patients; 1 of 6 DLTs will allow escalation again. 2 DLTs will require dose de-escalation. (NCT01887587)
Timeframe: 8 Weeks

Interventionmg (Number)
Modified VXLD Plus MLN97082.3

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Adverse Events.

Safety, tolerability will be assessed by counting the number of participants experiencing adverse events at 8 weeks post treatment. (NCT01887587)
Timeframe: Baseline to 30 days post treatment; approximately 8 weeks

Interventionparticipants (Number)
(Modified VXLD) Plus MLN97085

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Number of Participants Reporting Clinically Significant Change From Baseline in Laboratory Values

The number of participants with any markedly abnormal standard safety laboratory values collected throughout study. (NCT01912222)
Timeframe: Baseline up to Day 15 for each treatment cycle (28 days treatment cycle for up to a maximum of 12 cycles)

Interventionparticipants (Number)
Normal Hepatic Function (Ixazomib 4 mg)0
Moderate Hepatic Impairment (Ixazomib 2.3 mg)0
Severe Hepatic Impairment (Ixazomib 1.5 mg)0

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Unbound Cmax: Unbound Maximum Observed Plasma Concentration for Ixazomib

(NCT01912222)
Timeframe: Part A, Day 1: Pre-dose and at multiple timepoints (up to 336 hours) post-dose

Interventionnanogram per milliliter (ng/mL) (Geometric Mean)
Normal Hepatic Function (Ixazomib 4 mg)0.50893
Moderate Hepatic Impairment (Ixazomib 2.3 mg)0.37245
Severe Hepatic Impairment (Ixazomib 1.5 mg)0.23176

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Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) and Serious Adverse Events (SAE)

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. (NCT01912222)
Timeframe: Baseline up to 30 days after last dose of study drug (Day 45 for each treatment cycle for up to a maximum of 12 cycles [28 days treatment cycles])

,,
Interventionparticipants (Number)
TEAESAE
Moderate Hepatic Impairment (Ixazomib 2.3 mg)1510
Normal Hepatic Function (Ixazomib 4 mg)136
Severe Hepatic Impairment (Ixazomib 1.5 mg)2015

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Tmax- Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib

(NCT01912222)
Timeframe: Part A, Day 1: Pre-dose and at multiple timepoints (up to 336 hours) post-dose

Interventionhours (Median)
Normal Hepatic Function (Ixazomib 4 mg)0.950
Moderate Hepatic Impairment (Ixazomib 2.3 mg)1.500
Severe Hepatic Impairment (Ixazomib 1.5 mg)1.205

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Number of Participants Reporting Clinically Significant Change From Baseline in Vital Signs

Vital signs included body temperature (oral or tympanic measurement), sitting blood pressure (after the participant has rested for at least 5 minutes), and pulse (bpm). (NCT01912222)
Timeframe: Baseline up to Day 15 for each treatment cycle (28 days treatment cycle for up to a maximum of 12 cycles)

Interventionparticipants (Number)
Normal Hepatic Function (Ixazomib 4 mg)0
Moderate Hepatic Impairment (Ixazomib 2.3 mg)0
Severe Hepatic Impairment (Ixazomib 1.5 mg)0

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Unbound AUC(0-last): Unbound Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ixazomib

(NCT01912222)
Timeframe: Part A, Day 1: Pre-dose and at multiple timepoints (up to 336 hours) post-dose

Interventionnanogram*hours per milliliter (ng*hr/mL) (Geometric Mean)
Normal Hepatic Function (Ixazomib 4 mg)9.6476
Moderate Hepatic Impairment (Ixazomib 2.3 mg)7.3292
Severe Hepatic Impairment (Ixazomib 1.5 mg)4.4383

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Number of Participants With Overall Response Rate (ORR)

ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) as assessed by the investigator using the international Working Group criteria for participants CR: disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR: At least a 30 percent (%) decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions. (NCT01939899)
Timeframe: Baseline up to Day 15 Cycle 29 (approximately up to Day 802) or until PD or the start of alternate therapies

,,,,
Interventionparticipants (Number)
CRPRStable Disease (SD)PD
Lead-in Dose Finding Phase: Ixazomib 4 mg0012
Lead-in Dose Finding Phase: Ixazomib 5.3 mg0023
Lead-in Dose Finding Phase: Ixazomib 7.0 mg0023
Phase 2: PSMB1 Negative0001
Phase 2: PSMB1 Positive0147

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Duration of Response (DOR)

The DOR is defined as the time from the date of first documentation of a response to the date of first documented PD. Responders without documentation of PD will be censored at the date of last response assessment. DOR was categorized as CR+PR and CR. (NCT01939899)
Timeframe: Time from the date of first documentation of a response to the date of first documented PD (approximately up to Day 802)

Interventionmonths (Median)
Phase 2: PSMB1 Positive0.0328542094

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Phase 2: Number of Participants With Response Rates in PSMB1 Positive and PSMB1 Negative

(NCT01939899)
Timeframe: Baseline up to occurrence of disease progression, unacceptable toxicities, or discontinuation of study due to any other reasons (approximately up to Day 802)

Interventionparticipants (Number)
Phase 2: PSMB1 Positive12
Phase 2: PSMB1 Negative1

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Phase 2: Rate of Disease Control

Rate of disease control is defined as percentage of participants who achieved a SD or better for greater than or equal to (>=) 6 months. (NCT01939899)
Timeframe: Baseline or until occurrence of disease progression, unacceptable toxicities, or discontinuation of study due to any other reasons (approximately up to Day 805)

Interventionpercentage of participants (Number)
Phase 2: PSMB1 Positive16.7
Phase 2: PSMB1 NegativeNA

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Progression Free Survival (PFS)

PFS is defined as the time from the date of first dose of study treatment to the date of first documented PD or death. Participants without documentation of PD will be censored at the date of last response assessment that is SD or better. Participants without response assessment will be censored at the date of first dose. (NCT01939899)
Timeframe: Time from the date of first dose of study treatment to the date of first documented PD or death (approximately up to Day 802)

Interventionmonths (Median)
Lead-in Dose Finding: Ixazomib 5.3 mg (RP2D)1.9
Phase 2: PSMB1 Positive2.4
Phase 2: PSMB1 NegativeNA

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Time to Response (TTR)

TTR is defined as the time from the date of first dose of study treatment to the date of the first documentation of a PR or better response in a participant who responded. (NCT01939899)
Timeframe: Time from the date of first dose of study treatment to the date of first documented PR or better response or death (approximately up to Day 802)

Interventiondays (Median)
Phase 2: PSMB1 Positive560

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Lead-in Dose Finding Phase: AUC(0-168): Area Under the Plasma Concentration-time Curve From Time 0 to 168 Hours Postdose for Ixazomib

(NCT01939899)
Timeframe: Cycle 1, Days 1 and 15 pre-dose and at multiple time points (up to 168 hours) post-dose

,,
Interventionhour*nanogram per milliliter (h*ng/mL) (Mean)
Cycle 1 Day 1Cycle 1 Day 15
Lead-in Dose Finding Phase: Ixazomib 4 mg1265.00002440.0000
Lead-in Dose Finding Phase: Ixazomib 5.3 mg1030.14292007.0000
Lead-in Dose Finding Phase: Ixazomib 7.0 mg1680.33333120.0000

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Lead-in Dose Finding Phase: Cmax: Maximum Observed Plasma Concentration for Ixazomib

(NCT01939899)
Timeframe: Cycle 1, Days 1 and 15 pre-dose and at multiple time points (up to 168 hours) post-dose

,,
Interventionnanogram per milliliter (ng/mL) (Mean)
Cycle 1 Day 1Cycle 1 Day 15
Lead-in Dose Finding Phase: Ixazomib 4 mg141.3333124.2667
Lead-in Dose Finding Phase: Ixazomib 5.3 mg103.4717144.0667
Lead-in Dose Finding Phase: Ixazomib 7.0 mg121.1167152.0667

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Lead-in Dose Finding Phase: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib

(NCT01939899)
Timeframe: Cycle 1, Days 1 and 15 pre-dose and at multiple time points (up to 168 hours) post-dose

,,
Interventionhour (Median)
Cycle 1 Day 1Cycle 1 Day 15
Lead-in Dose Finding Phase: Ixazomib 4 mg1.00001.0000
Lead-in Dose Finding Phase: Ixazomib 5.3 mg1.00000.7500
Lead-in Dose Finding Phase: Ixazomib 7.0 mg1.05001.0000

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Number of Participants Experiencing 1 or More Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

(NCT01939899)
Timeframe: Baseline up to 30 days after last dose of study drug (approximately up to Day 832)

,,,,
Interventionparticipants (Number)
TEAESAE
Lead-in Dose Finding Phase: Ixazomib 4 mg31
Lead-in Dose Finding Phase: Ixazomib 5.3 mg73
Lead-in Dose Finding Phase: Ixazomib 7.0 mg64
Phase 2: PSMB1 Negative11
Phase 2: PSMB1 Positive114

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Ixazomib and Metabolites as Percent of Total Radioactivity in Plasma

"The plasma samples were pooled for participants over 816 hrs post-dose, and data was analysed using the Hamilton method time-proportional pooling, and therefore the data is reported as percent of total radioactivity in plasma with measure type as number and measure dispersion as Not applicable, NA." (NCT01953783)
Timeframe: Day 1 pre-dose and at multiple time points (up to 816 hrs) post-dose

Interventionpercent of total radioactivity in plasma (Number)
P4, ixazomibP2, ML00701258P3, ML00701201P6, ML00749506P7, ML00752034
Ixazomib54.27.9118.910.63.20

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Ixazomib and Metabolites as Percent of Total Dose Administered in Urine

"The 35-day post-dose data is extrapolated from the average of four participant data from 0-168-hr pooled urine. The data is therefore reported as percentage of dose with measure type as number and measure dispersion as NA." (NCT01953783)
Timeframe: Day 1 pre-dose and at multiple time points (up to Day 35) post-dose

Interventionpercentage of dose (Number)
U9, ixazomibU1U2U3U4U5, ML00701258U6, ML00701201U7U8U10, ML00751996U11, ML00749506U12, ML00752034U13
Ixazomib1.300.3910.9261.611.332.7230.22.750.6955.931.280.0690.974

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Ixazomib and Metabolites as Percent of Total Dose Administered in Feces

"The 35-day post-dose data is extrapolated from the average of four participant data from 0-168-hr pooled feces. The data is therefore reported as percentage of dose with measure type as number and measure dispersion as NA." (NCT01953783)
Timeframe: Day 1 pre-dose and at multiple time points (up to Day 35) post-dose

Interventionpercentage of dose (Number)
FH6, ixazomibFH1FH2FH3, ML00701258FH4, ML00701201FH5FH7, ML00752034FH8FH9
Ixazomib13.80.9000.1110.6200.9011.141.580.5020.112

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Part A: Tmax: Time to Reach the Maximum Observed Whole Blood Concentration (Cmax) for TRA

Time to reach the maximum observed whole blood concentration (Cmax) for TRA, equal to time (hours) to Cmax for TRA after administration, obtained directly from the whole blood TRA concentration-time curve. (NCT01953783)
Timeframe: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) post-dose

Interventionhr (Median)
Ixazomib0.6000

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Part A: Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for Ixazomib

Time to reach the maximum observed plasma concentration (Cmax), equal to time (hours) to Cmax of ixazomib after administration, obtained directly from the plasma concentration-time curve. (NCT01953783)
Timeframe: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 14) post-dose

Interventionhour (hr) (Median)
Ixazomib0.5000

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Part A: Renal Clearance of Ixazomib

Renal clearance is the volume of plasma from which ixazomib is completely removed by the kidney in a given amount of time, calculated as the amount of ixazomib excreted in the urine divided by the area under the plasma ixazomib concentration-time curve. (NCT01953783)
Timeframe: Day 1 pre-dose and at multiple timepoints (up to Day 14) post-dose

Interventionliter per hour (L/hr) (Geometric Mean)
Ixazomib0.1191

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Part A: Cumulative Percentage of the Total Radioactivity Dose Excreted in Urine

Percentage of the TRA dose excreted in urine from Day 1 to Day 35 of Part A. (NCT01953783)
Timeframe: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) post-dose

Interventionpercentage of dose (Mean)
Ixazomib62.06

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Part A: Tmax: Time to Reach the Cmax for TRA

Time to reach the maximum observed plasma concentration (Cmax) for TRA, equal to time (hours) to Cmax for TRA after administration, obtained directly from the plasma TRA concentration-time curve. (NCT01953783)
Timeframe: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) post-dose

Interventionhr (Median)
Ixazomib0.5000

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Part A: Cumulative Percentage of the Total Radioactivity Dose Excreted in Feces

Percentage of the TRA dose excreted in feces from Day 1 to Day 35 of Part A (NCT01953783)
Timeframe: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) post-dose

Interventionpercentage of dose (Mean)
Ixazomib21.80

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Part A: Cumulative Percentage of Ixazomib Dose Recovered in the Urine

Percentage of the ixazomib dose excreted unchanged in the urine from 0 to 168 hrs post-dose. (NCT01953783)
Timeframe: Day 1 of Part A from 0 to pre-dose and at multiple timepoints (up to 168 hrs) post-dose

Interventionpercentage of dose (Mean)
Ixazomib3.226

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Part A: Cmax: Maximum Observed Plasma Concentration of TRA

Maximum observed plasma concentration (Cmax) of TRA is the peak plasma concentration of TRA, obtained directly from the plasma TRA concentration-time curve. (NCT01953783)
Timeframe: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) post-dose

Interventionnanogram-equivalent per milliliter (Geometric Mean)
Ixazomib78.80

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Part A: Cmax: Maximum Observed Plasma Concentration for Ixazomib

Maximum observed plasma concentration (Cmax) is the peak plasma concentration of ixazomib, obtained directly from the plasma concentration-time curve. (NCT01953783)
Timeframe: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 14) post-dose

Interventionnanogram per milliliter (ng/mL) (Geometric Mean)
Ixazomib89.06

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Part A: AUC(0-816): Area Under the Whole Blood Concentration-time Curve From Time 0 to 816 Hrs Post-dose for TRA

AUC(0-816) is a measure of the area under the whole blood concentration time-curve from time zero to 816 hrs post-dose for TRA. (NCT01953783)
Timeframe: Day 1 of Part A pre-dose and at multiple timepoints (up to 816 hrs) post-dose

Interventionnanogram-equivalent* hour per milliliter (Geometric Mean)
Ixazomib29200

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Part A: AUC(0-816): Area Under the Plasma Concentration-time Curve From Time 0 to 816 Hrs Post-dose for TRA

AUC(0-816) is a measure of the area under the plasma concentration time-curve from time zero to 816 hrs post-dose for TRA. (NCT01953783)
Timeframe: Day 1 of Part A pre-dose and at multiple timepoints (up to 816 hrs) post-dose

Interventionnanogram-equivalent*hour per milliliter (Geometric Mean)
Ixazomib2981

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Part A: Cmax: Maximum Observed Whole Blood Concentration of TRA

Maximum observed whole blood concentration (Cmax) of a TRA is the peak whole blood concentration of TRA, obtained directly from the whole blood TRA concentration-time curve. (NCT01953783)
Timeframe: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) post-dose

Interventionnanogram-equivalent per milliliter (Geometric Mean)
Ixazomib181.6

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Part A: AUC(0-312): Area Under the Plasma Concentration-time Curve From Time 0 to 312 Hrs Post-dose for Ixazomib

AUC(0-312) is a measure of the area under the plasma concentration time-curve from time zero to 312 hrs post-dose for ixazomib. (NCT01953783)
Timeframe: Day 1 of Part A pre-dose and at multiple timepoints (up to 312 hrs) post-dose

Interventionnanogram*hour per milliliter (ng*hr/mL) (Geometric Mean)
Ixazomib1181

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Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

(NCT01953783)
Timeframe: Baseline up to Cycle 5 Day 45

Interventionparticipants (Number)
TEAEsSAEs
Ixazomib71

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Progression Free Survival (PFS) for All Patients on the Pomalidomide/Dexamethasone Arm at the Time of Cross-over to Pomalidomide/Dexamethasone/Ixazomib (Phase II)

(NCT02004275)
Timeframe: Up to 3 years post-registration (at crossover)

Interventionmonths (Median)
Arm I (Pomalidomide, Dexamethasone)5.6

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Overall Response Rate (ORR)

ORR is defined as partial response (PR), very good partial response (VGPR), complete response (CR), or stringent complete response (sCR) according to International Myeloma Working Group (IMWG) Uniform Response Criteria (NCT02004275)
Timeframe: 3 years

Interventionproportion of participants (Number)
Arm I (Pomalidomide, Dexamethasone).436
Arm II (Pomalidomide, Dexamethasone, Ixazomib).632

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Response Rates (Overall Response Rate (ORR), Clinical Benefit Rate (CBR), Disease Control Rate (DCR) for All Patients on the Pomalidomide/Dexamethasone Arm at the Time of Cross-over to Pomalidomide/Dexamethasone/Ixazomib (Phase II)

(NCT02004275)
Timeframe: Up to 3 years

Interventionproportion of partcipants (Number)
Overall Response RateClinical Benefit RateDisease Control Rate
Arm I(Pomalidomide, Dexamethasone).231.269.962

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Baseline Level of Perceived Fatigue and QOL, Assessed Using the Registration Fatigue/Uniscale Assessment Form (Phase II)

Pre-treatment patient-report of fatigue and overall quality of life (based on a 10-point Likert scale). A higher number indicates a better quality of life where 10 is the best outcome and 0 is the worst. (NCT02004275)
Timeframe: baseline

,
Interventionparticipants (Number)
High QoL(7-10)Medium or Low QoL (0-7)
Arm I (Pomalidomide, Dexamethasone)2116
Arm II (Pomalidomide, Dexamethasone, Ixazomib)2711

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Progression Free Survival (PFS) (Phase II)

progression-free survival (PFS), defined as the time from randomization to the date the International Myeloma Working Group (IMWG) criteria for disease progression is met. If a patient initiates another anti-cancer treatment prior to disease progression, they will be censored at the date of initiation of this treatment. Patients will be randomized to treatment using the Pocock-Simon algorithm balancing the distribution of the following stratification factors between the two treatment arms: 1) ISS 1-2 disease vs. ISS 3 disease (current ISS stage based off screening beta 2 microglobulin and albumin) 2) High risk cytogenetics features: yes vs. no High risk cytogenetics features include: del(1p), gain of 1q, t(4;14), t(14;16), t(14; 20), del(17p) 3) Prior treatment with a proteasome inhibitor: yes vs. no (NCT02004275)
Timeframe: 3 years

Interventiondays (Median)
Phase II Arm I (Pomalidomide, Dexamethasone)228
Phase II Arm II (Pomalidomide, Dexamethasone, Ixazomib)619

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Overall Survival (OS) (Phase II)

Overall survival was analyzed from the time of registration to the date of death or last known date living. Due to median OS time not being reached due to lack of deaths at the time of this report by either arm, the 2 year OS rate has been reported. This analysis censors living patients at 2 years. (NCT02004275)
Timeframe: 2 years

Interventionproportion of patients alive (Number)
Phase II Arm I (Pomalidomide, Dexamethasone).795
Phase II Arm II (Pomalidomide, Dexamethasone, Ixazomib).784

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Maximum Tolerated Dose (MTD) of Pomalidomide and Ixazomib, Determined According to Incidence of Dose Limiting Toxicity (DLT) Graded Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (Phase I)

For this protocol, dose-limiting toxicity (DLT) will be defined by the following adverse events at least possibly related to study therapy: Grade 3 or higher non-hematologic toxicity, with the following exceptions: Alopecia is not expected but would not be considered a DLT. Nausea, vomiting and diarrhea will only be considered a DLT if it cannot be adequately managed with optimal supportive care. Grade 3 or 4 hyperglycemia due to dexamethasone will only be considered a DLT if it cannot be controlled with appropriate therapy Grade 4 hematologic toxicity, with the following exceptions: Grade 4 lymphopenia is expected with this regimen and will not be construed as a DLT. Grade 4 neutropenia will only be considered a DLT if it lasts longer than 7 days despite appropriate supportive care. Grade 4 thrombocytopenia will only be considered a DLT if it lasts longer than 7 days or is associated with greater then or equal to grade 3 bleeding event (NCT02004275)
Timeframe: 28 days

Interventionparticipants with DLT (Number)
Phase 1 Dose Level 10
Phase 1 Dose Level 20
Phase 1 Dose Level 31
Phase 1 Dose Level 41

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Incidence, Type and Severity of Adverse Events, Graded According to National Cancer Institute (NCI) Common Terminology Criteria Adverse Events (CTCAE) Version 4.0 (Phase II)

The count of paitents that experenced an adverse event is reported in this section. A full table of these events is reported in the adverse event section of this report. (NCT02004275)
Timeframe: 92 months

InterventionParticipants (Count of Participants)
Phase II Arm I (Pomalidomide, Dexamethasone)22
Phase II Arm II (Pomalidomide, Dexamethasone, Ixazomib) + Crossover Patients From Arm I33
Phase 1 Dose Level 12
Phase 1 Dose Level 22
Phase 1 Dose Level 34
Phase 1 Dose Level 46

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Incidence of Dose Reductions/Delays (Phase I)

(NCT02004275)
Timeframe: 39 months

InterventionParticipants (Count of Participants)
Phase 1 Dose Level 12
Phase 1 Dose Level 23
Phase 1 Dose Level 36
Phase 1 Dose Level 45

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Incidence and Type of Dose Limiting Toxicities (DLTs) Graded According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (Phase I)

These events are reported in the adverse events section of this report. (NCT02004275)
Timeframe: 44.5 months

Interventionparticipants with DLT (Number)
Phase 1 Dose Level 10
Phase 1 Dose Level 20
Phase 1 Dose Level 31
Phase 1 Dose Level 41

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Duration of Response (DOR), Calculated for All Patients Achieving an Objective Response, Partial Response (PR) or Better (Phase II)

(NCT02004275)
Timeframe: Up to 3 years

InterventionMonths (Median)
Phase II Arm I (Pomalidomide, Dexamethasone)12.3
Phase II Arm II (Pomalidomide, Dexamethasone, Ixazomib)23.7

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Disease Control Rate (DCR), Defined as Stable Disease (SD) and Better According to International Myeloma Working Group (IMWG) Uniform Response Criteria (Phase II)

Proportion of patients that went two of more cycles of treatment without discontinuing treatment for progression or intolerability. (NCT02004275)
Timeframe: 42 days

Interventionproportion of partcipants (Number)
Phase II Arm I (Pomalidomide, Dexamethasone).949
Phase II Arm II (Pomalidomide, Dexamethasone, Ixazomib).921

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Clinical Benefit Rate (CBR)

Disease response status is based on the IMWG criteria being held for two consecutive evaluations at least 4 weeks apart. Clinical benefit rate (CBR) is defined as proportion of patients with minimal response (MR) and better according to International Myeloma Working Group (IMWG) Uniform Response Criteria (Phase II) (NCT02004275)
Timeframe: 3 years

Interventionproportion of participants (Number)
Phase II Arm I (Pomalidomide, Dexamethasone).564
Phase II Arm II (Pomalidomide, Dexamethasone, Ixazomib).737

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Overall Survival (OS)

Overall survival (OS) from time of study entry to the earlier of death from any cause or end of follow up at 1 year (NCT02030405)
Timeframe: 1 year

InterventionParticipants (Count of Participants)
Ixazomib (MLN9708)0

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Overall Response Rate (ORR)

"Overall response rate after 3 cycles of treatment (9 weeks) was assessed as complete remission (CR); CR with incomplete recovery (CRi); and partial remission (PR) with MLN9708, in participants with NPM1-mutated AML by LeukemiaNet1 guidelines:~Although achievement of complete remission (CR) has unique clinical significance for improved overall survival (OS) and relapse-free survival (RFS) compared to achievement of CRi with incomplete platelet recovery, the latter is still a clinically meaningful response, as it is independently-superior to resistant disease.~Partial remission (PR) is defined as meeting all hematologic criteria for CR with an allowance for 5% to 25% bone marrow blasts or decrease of pre-treatment bone marrow blast percentage by at least 50%.~Stable disease is defined as a change in bone marrow aspirate blast count within 10% of baseline.~Relapsed disease is defined as reappearance of blasts in the blood or bone marrow blasts" (NCT02030405)
Timeframe: 9 weeks

InterventionParticipants (Count of Participants)
Complete Remission (CR)Complete Remission with incomplete recovery (CRi)Partial Remission (PR)Stable Disease (SD)Relapsed Disease (RD)Progressive Disease (PD)
Ixazomib (MLN9708)000002

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Tmax: Time to First Occurrence of Cmax for Ixazomib in RRMM Participants

(NCT02046070)
Timeframe: Cycle 1 Days 1 and 15 predose and at multiple timepoints (up to 168) hours postdose

Interventionhr (Median)
Cycle 1 Day 1Cycle 1 Day 15
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (RRMM)1.2252.000

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Percentage of Participants With CR + VGR + PR (ORR), CR, VGPR, and PR in NDMM Participants Remaining on Treatment After 13 Cycles

Percentage of participants with Overall Response (CR + VGPR + PR), CR, VGPR and PR according to IMWG criteria. CR=negative immunofixation of serum and urine; disappearance of soft tissue plasmacytomas;<5% PC in bone marrow. VGPR=serum and urine M-component detectable by immunofixation but not on electrophoresis or 90% reduction in serum M-component plus urine M-component <100 mg/24 hour. PR=50% reduction of serum M-protein and reduction in 24 hour urine M-protein by 90% or <200 mg/24 hour or decrease 50% difference between involved FLC levels or 50% reduction in bone marrow plasma cells if baseline percentage was 30%; and if present at Baseline, 50% reduction in the size of soft tissue plasmacytomas. (NCT02046070)
Timeframe: Day 1 of each 28-day Cycle (Up to 45 months)

,
Interventionpercentage of participants (Number)
CR + VGPR + PRCRVGPRPR
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM)75.016.720.837.5
Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM)85.719.028.638.1

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Combined Response Rate During the Induction Phase in Newly Diagnosed Multiple Myeloma (NDMM) Participants

Combined Response Rate is the percentage of participants with Complete Response (CR), including stringent Complete Response (sCR), and Very Good Partial Response (VGPR) according to the International Myeloma Working Group (IMWG) criteria during the Induction Phase (Cycles 1-13, 28-day cycles). CR=negative immunofixation of serum and urine, disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow. VGPR=serum and urine M-component detectable by immunofixation but not on electrophoresis or 90% reduction in serum M-component plus urine M-component <100 mg/24 hour. (NCT02046070)
Timeframe: Day 1 of Cycles 1-13, 28-day cycles (Up to 1 year)

Interventionpercentage of participants (Number)
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM)27
Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM)24

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Duration of Response (DOR) in NDMM Participants

DOR is defined as the time from the date of first documentation of a confirmed PR or better to the date of first documented PD up to the initiation of alternative therapy. (NCT02046070)
Timeframe: Up to 45 Months

Interventionmonths (Median)
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM)32.2
Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM)36.6

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Duration of Response (DOR) in RRMM Participants

DOR is defined as the time from the date of first documentation of a confirmed PR or better to the date of first documented PD up to the alternative therapy. (NCT02046070)
Timeframe: Up to 45 months

Interventionmonths (Median)
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (RRMM)26.3

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Tmax: Time to First Occurrence of Cmax for Ixazomib in NDMM Participants

(NCT02046070)
Timeframe: Cycle 1 Days 1 and 15 predose and at multiple timepoints (up to 168 hours) postdose

,
Interventionhour (hr) (Median)
Cycle 1 Day 1Cycle 1 Day 15
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM)1.2501.000
Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM)1.0401.000

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Percentage of Participants With CR + VGPR + PR (ORR), CR, VGPR, PR and Stable Disease (SD), Progressive Disease (PD) During the Induction Phase

Percentage of participants with CR + VGPR + PR (ORR), CR, VGPR, PR, SD, PD according to IMWG criteria. CR=negative immunofixation of serum and urine; disappearance of soft tissue plasmacytomas;<5% PC in bone marrow. VGPR=serum and urine M-component detectable by immunofixation but not on electrophoresis or 90% reduction in serum M-component plus urine M-component <100 mg/24 hour. PR=50% reduction of serum M-protein and reduction in 24 hour urine M-protein by 90% or <200 mg/24 hour or decrease 50% difference between involved FLC levels or 50% reduction in bone marrow plasma cells if baseline percentage was 30%; and if present at Baseline, 50% reduction in the size of soft tissue plasmacytomas. SD=not meeting criteria for VGPR, PR or PD. PD=25% increase in lowest value any of the following: serum M-component, urine M-component, difference between involved and uninvolved FLC levels, bone marrow PC percentage; new or increase in size of existing bone lesions or soft tissue plasmacytomas. (NCT02046070)
Timeframe: Day 1 of Cycles 1-13, 28-day cycles (Up to 1 year)

,
Interventionpercentage of participants (Number)
CR + VGPR + PRCRVGPRPRSDPD
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM)79121567120
Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM)7191562183

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Overall Response Rate (ORR) in Relapsed and/or Refractory Multiple Myeloma (RRMM) Participants

ORR is the percentage of participants with CR, VGPR or PR according to IMWG criteria. CR=negative immunofixation of serum and urine, disappearance of any soft tissue plasmacytomas and <5% plasma cells (PC) in bone marrow. VGPR=serum and urine M-component detectable by immunofixation but not on electrophoresis or 90% reduction in serum M-component plus urine M-component <100 mg/24 hour. PR=50% reduction of serum M-protein and reduction in 24 hour urine M-protein by 90% or <200 mg/24 hour or decrease 50% difference between involved free light chain (FLC) levels or 50% reduction in bone marrow plasma cells if baseline percentage was 30%; and if present at Baseline, 50% reduction in the size of soft tissue plasmacytomas. (NCT02046070)
Timeframe: Day 1 of each 28 day cycle (Up to 45 months)

Interventionpercentage of participants (Mean)
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (RRMM)49

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AUCtau: Area Under the Concentration-time Curve During a Dosing Interval for Ixazomib in NDMM Participants

(NCT02046070)
Timeframe: Cycle 1 Days 1 and 15 predose and at multiple timepoints (up to 168 hours) postdose

,
Interventionhr*ng/mL (Mean)
Cycle 1 Day 1Cycle 1 Day 15
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM)885.1671338.333
Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM)792.6001226.600

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Progression Free Survival (PFS) in NDMM Participants

PFS is defined as the time from the date of first dose of study treatment to the date of the first documented disease progression or death. (NCT02046070)
Timeframe: Up to 45 months

Interventionmonths (Median)
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM)23.5
Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM)23.0

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Progression Free Survival (PFS) in RRMM Participants

PFS is defined as the time from the date of first dose of study treatment to the date of the first documented disease progression or death. (NCT02046070)
Timeframe: Up to 45 months

Interventionmonths (Median)
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (RRMM)14.2

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Time to Progression (TTP) in NDMM Participants

TTP is defined as the time from the date of first dose of study treatment to the date of first documentation of disease progression. (NCT02046070)
Timeframe: Up to 45 months

Interventionmonths (Median)
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM)30.9
Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM)32.2

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Time to Progression (TTP) in RRMM Participants

TTP is defined as the time from the date of first dose of study treatment to the date of first documentation of disease progression. (NCT02046070)
Timeframe: Up to 45 months

Interventionmonths (Median)
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (RRMM)16.8

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Time to Response (TTR) in NDMM Participants During the Induction Phase

TTR is defined as the time interval from the date of the first dose of study treatment to the date of the first documented confirmed response of PR or better up to the initiation of alternative therapy in a participant who responded. (NCT02046070)
Timeframe: Up to 1 year

Interventionmonths (Median)
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM)2.2
Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM)1.9

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AUCtau: Area Under the Concentration-time Curve During a Dosing Interval for Ixazomib in RRMM Participants

(NCT02046070)
Timeframe: Cycle 1 Days 1 and 15 predose and at multiple timepoints (up to 168 hours) postdose

Interventionhr*ng/mL (Mean)
Cycle 1 Day 1Cycle 1 Day 15
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (RRMM)518.1671241.000

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Change From Baseline in EORTC Quality of Life Questionnaire (QLQ-C30) in RRMM Participants

EORTC QLQ-C30 is a patient completed 30 item questionnaire that consists of 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The patient evaluates their health status over the previous week. There are 28 questions answered on a 4-point scale where1=Not at all (best) to 4=Very Much (worst) and 2 questions answered on a 7-point scale where 1=Very poor (worst) to 7= Excellent (best). All of the scales and single-item measures are transformed to a score:0 to 100. For functioning scales and global QOL higher scores indicate better functioning (a positive change from Baseline indicates improvement); for symptom scales higher scores indicate more severe symptoms (a negative change from Baseline indicates improvement). (NCT02046070)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of End of Treatment (EOT) (Up to 45 months)

Interventionscore on a scale (Mean)
Global Health Status/QoL, Change from BL at EOTPhysical functioning, Change from BL at EOTRole functioning, Change from BL at EOTEmotional functioning, Change from BL at EOTCognitive functioning, Change from BL at EOTSocial functioning, Change from BL at EOTFatigue, Change from BL at EOTNausea/Vomiting, Change from BL at EOTPain, Change from BL at EOTDyspnea, Change from BL at EOTInsomnia, Change from BL at EOTAppetite Loss, Change from BL at EOTConstipation, Change from BL at EOTDiarrhea, Change from BL at EOTFinancial Difficulties, Change from BL at EOT
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (RRMM)-5.50-6.00-7.67-5.00-5.33-11.335.113.335.0010.00-6.004.672.006.004.00

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Time to Response (TTR) in RRMM Participants

TTR is defined as the time interval from the date of the first dose of study treatment to the date of the first documented confirmed response of PR or better up to the alternative therapy in a participant who responded. (NCT02046070)
Timeframe: Up to 45 months

Interventionmonths (Median)
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (RRMM)2.1

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Cmax: Maximum Observed Plasma Concentration for Ixazomib in NDMM Participants

(NCT02046070)
Timeframe: Cycle 1 Days 1 and 15 predose and at multiple timepoints (up to 168 hours) postdose

,
Interventionnanogram/mL (ng/mL) (Mean)
Cycle 1 Day 1Cycle 1 Day 15
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM)64.28353.145
Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM)46.60062.280

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Cmax: Maximum Observed Plasma Concentration for Ixazomib in RRMM Participants

(NCT02046070)
Timeframe: Cycle 1 Days 1 and 15 predose and at multiple timepoints (up to 168 hours) postdose

Interventionng/mL (Mean)
Cycle 1 Day 1Cycle 1 Day 15
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (RRMM)47.40052.229

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Number of Participants With Adverse Events (AEs), Grade 3 or Higher AEs, AEs Resulting in Treatment Discontinuation, AEs Resulting in Dose Reduction and Serious Adverse Events (SAEs) in NDMM Participants

"An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. This includes any newly occurring event, or a previous condition that has increased in severity or frequency since the administration of study drug.~A SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is a medically important event. Relationship of each AE to study drug was determined by the Investigator." (NCT02046070)
Timeframe: First dose of study drug through 30 days after last dose of drug (Up to 45 months)

,
InterventionParticipants (Count of Participants)
Any AEGrade 3 or Higher AEsAEs Resulting in Treatment DiscontinuationAEs Resulting in Dose ReductionSAEs
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM)352791117
Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM)3427111020

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Number of Participants With AEs, Grade 3 or Higher AEs, AEs Resulting in Treatment Discontinuation, AEs Resulting in Dose Reduction, SAEs in RRMM Participants

"An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment.~A SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is a medically important event. Relationship of each AE to study drug was determined by the Investigator." (NCT02046070)
Timeframe: First dose of study drug through 30 days after last dose of drug (Up to 45 months)

InterventionParticipants (Count of Participants)
Any AEGrade 3 or Higher AEAEs Resulting in Treatment DiscontinuationAEs Resulting in Dose ReductionSAEs
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (RRMM)7249193030

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Number of Participants With AEs, SAEs, AEs Resulting in Discontinuation and AEs Resulting in Dose Reduction in NDMM Participants Remaining on Treatment After 13 Cycles

"An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. This includes any newly occurring event, or a previous condition that has increased in severity or frequency since the administration of study drug.~A SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is a medically important event. Relationship of each AE to study drug was determined by the Investigator." (NCT02046070)
Timeframe: First dose of study drug through 30 days after the last dose of drug (Up to 45 months)

,
InterventionParticipants (Count of Participants)
Any AESAEAEs Resulting in Treatment DiscontinuationAEs Resulting in Dose Reduction
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM)22615
Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM)20424

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Percentage of Participants With (CR + VGPR), CR, VGPR, PR, SD and PD in RRMM Participants

Percentage of participants with CR + VGPR + PR (ORR), CR, VGPR, PR, SD, PD according to IMWG criteria. CR=negative immunofixation of serum and urine; disappearance of soft tissue plasmacytomas;<5% PC in bone marrow. VGPR=serum and urine M-component detectable by immunofixation but not on electrophoresis or 90% reduction in serum M-component plus urine M-component <100 mg/24 hour. PR=50% reduction of serum M-protein and reduction in 24 hour urine M-protein by 90% or <200 mg/24 hour or decrease 50% difference between involved FLC levels or 50% reduction in bone marrow plasma cells if baseline percentage was 30%; and if present at Baseline, 50% reduction in the size of soft tissue plasmacytomas. SD=not meeting criteria for VGPR, PR or PD. PD=25% increase in lowest value any of the following: serum M-component, urine M-component, difference between involved and uninvolved FLC levels, bone marrow PC percentage; new or increase in size of existing bone lesions or soft tissue plasmacytomas. (NCT02046070)
Timeframe: Day 1 of each 28-day Cycle (Up to 45 months)

Interventionpercentage of participants (Number)
CR + VGPRCRVGPRPRSDPD
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (RRMM)19514443710

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Percentage of Participants With CR + VGPR + PR (ORR), CR + VGPR, CR, VGPR, PR, SD and PD Throughout the Entire Treatment Period in NDMM Participants

Percentage of participants with CR + VGPR + PR (ORR), CR, VGPR, PR, SD, PD according to IMWG criteria. CR=negative immunofixation of serum and urine; disappearance of soft tissue plasmacytomas;<5% PC in bone marrow. VGPR=serum and urine M-component detectable by immunofixation but not on electrophoresis or 90% reduction in serum M-component plus urine M-component <100 mg/24 hour. PR=50% reduction of serum M-protein and reduction in 24 hour urine M-protein by 90% or <200 mg/24 hour or decrease 50% difference between involved FLC levels or 50% reduction in bone marrow plasma cells if baseline percentage was 30%; and if present at Baseline, 50% reduction in the size of soft tissue plasmacytomas. SD=not meeting criteria for VGPR, PR or PD. PD=25% increase in lowest value any of the following: serum M-component, urine M-component, difference between involved and uninvolved FLC levels, bone marrow PC percentage; new or increase in size of existing bone lesions or soft tissue plasmacytomas. (NCT02046070)
Timeframe: Day 1 of each 28-day Cycle (Up to 45 months)

,
Interventionpercentage of participants (Number)
CR + VGPR + PRCR + VGPRCRVGPRPRSDPD
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM)8236152167180
Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM)7132122159186

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Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) During the Induction Phase in NDMM Participants

EORTC QLQ-C30 is a patient completed 30 item questionnaire that consists of 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The patient evaluates their health status over the previous week. There are 28 questions answered on a 4-point scale where1=Not at all (best) to 4=Very Much (worst) and 2 questions answered on a 7-point scale where 1=Very poor (worst) to 7= Excellent (best). All of the scales and single-item measures are transformed to a score:0 to 100. For functioning scales and global QOL higher scores indicate better functioning (a positive change from Baseline indicates improvement); for symptom scales higher scores indicate more severe symptoms (a negative change from Baseline indicates improvement). (NCT02046070)
Timeframe: Baseline (BL) (Day 1 of Cycle 1), Day 1 of Cycle 13 (Up to 1 year)

,
Interventionscore on a scale (Mean)
Global Health Status/QoL, Change from BL; Cycle 13Physical functioning, Change from BL at Cycle 13Role functioning, Change from BL at Cycle 13Emotional functioning, Change from BL at Cycle 13Cognitive functioning, Change from BL at Cycle 13Social functioning, Change from BL at Cycle 13Fatigue, Change from BL at Cycle 13Nausea/Vomiting, Change from BL at Cycle 13Pain, Change from BL at Cycle 13Dyspnea, Change from BL at Cycle 13Insomnia, Change from BL at Cycle 13Appetite Loss, Change from BL at Cycle 13Constipation, Change from BL at Cycle 13Diarrhea, Change from BL at Cycle 13Financial Difficulties, Change from BL at Cycle 13
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM)3.4714.178.3311.342.789.03-10.88-4.86-13.89-11.11-16.67-18.06-13.89-2.784.17
Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM)-5.4317.976.522.54-7.25-11.59-6.76-4.35-10.87-7.25-10.14-7.25-5.805.801.45

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Response to Combination Therapy (Panobinostat, Dexamethasone, MLN9708)

Response to intervention as measured by international uniform response criteria and clinical benefit response according to modified EBMT response criteria, comparing myeloma panels obtained at the beginning of each cycle that include SPEP, 24 h UPEP, serum and urine IFEs, and serum free light chains to results at screening. In addition a baseline bone marrow exam and skeletal survey will be obtained and repeated as clinically indicated and for assessment of complete remission (bone marrow) (NCT02057640)
Timeframe: 4 months (102 days)

Interventionparticipants (Number)
DL1 - 3mg Lxazomib0
DL2 - 4mg Lxazomib0

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Overall Survival

Overall survival for all will be the number of months from study entry to death from any cause. (NCT02057640)
Timeframe: up to 3 years from start of treatment

Interventionmonths (Median)
DL1 - 3mg Lxazomib12.8
DL2 - 4mg Lxazomib17.6

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Number of Participants With Dose Limiting Toxicity According to CTCAE Version 4.03

Number of Participants with Dose Limiting Toxicity of MLN9708 (lxazomib) according to CTCAE version 4.03 (NCT02057640)
Timeframe: at 28 days from start of treatment

InterventionParticipants (Count of Participants)
Dose Levels 14

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Progression-free Survival

"Progression-free survival will be the number of days from study entry to progression or death of any cause, whichever comes first.~Progression-free survival is survival with absence of progressive disease, defined by~An increase of 25% from lowest response value in any one or more of the following:~Serum M-component (absolute increase must be >0.5 g/100 ml) *~Urine M-component (absolute increase must be >200mg per 24 h)~Only in patients without measurable serum and urine M-protein levels: the difference between involved and uninvolved FLC levels (absolute increase must be >100 mg/l)~Bone marrow plasma cell percentage (absolute % must be >10%)~And / or:~Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas~Development of hypercalcemia (corrected serum calcium >11.5 mg/100 ml) that can be attributed solely to the plasma cell proliferative disorder" (NCT02057640)
Timeframe: 1 year from start of treatment

Interventionmonths (Median)
DL1 - 3mg Lxazomib1.2
DL2 - 4mg Lxazomib3.5

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Maximum Tolerated Dose (MTD) of MLN9708 (Phase I)

The highest dose level that produces 1/6 dose-limiting toxicities (DLTs) in Cycle #1 will be the maximum tolerated dose (MTD). The RP2D of ixazomib and pomalidomide will generally be the MTD, but it may be less than the MTD based on a review of available data/cumulative toxicities from phase I. (NCT02119468)
Timeframe: From the initial treatment to Day 28 (Cycle #1)

Interventionmg (Number)
Dose Level #2 (4mg MLN9708)4

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Number of Patients With Dose-Limiting Toxicities (Phase I)

Dose Limiting Toxicity (DLT) is defined as any of the toxicities in Section 7.3 that are at least possibly related to either Pomalidomide or MLN9708 that occur during cycle 1. Toxicity graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.03. The highest dose level that produces 1/6 dose-limiting toxicities (DLTs) in course 1 will be the maximum tolerated dose (MTD). The RP2D of ixazomib and pomalidomide will generally be the MTD, but it may be less than the MTD based on a review of available data/cumulative toxicities from phase I. (NCT02119468)
Timeframe: From the initial treatment to Day 28 (Cycle #1)

InterventionParticipants (Count of Participants)
Dose Level #1: 3mg MLN97081
Dose Level #2: 4mg MLN97081

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One-Year Progression-Free Survival at the Recommend Phase II Dose (RP2D)

Progression-free survival (PFS) was defined as time from initial treatment to recurrence, progression or death. In a clinical trial, measuring the progression-free survival is one way to see how well a new treatment works. Progression-free survival was estimated using the Kaplan-Meier method; the 95% confidence interval was calculated using Greenwood's formula [Breslow NE, Day NE. Statistical methods in cancer research: volume II, the design and analysis of cohort studies. IARC Sci Publ 1987;82:1-406.] (NCT02119468)
Timeframe: Date of first dose of study drug to first documented disease relapse, progression or death from any cause, whichever occurs first, up to 24 months. And the median follow-up for the surviving patients is at least one year.

InterventionPercentage of Participants (%) (Number)
Dose Level #2 (4mg MLN9708)34

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Median Overall Survival Time

Overall Survival (OS) is defined as the time from study start until death. (NCT02158975)
Timeframe: 24 months after initiation of study treatment

Interventionmonths (Median)
MLN9708NA

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Median Progression Free Survival Time

Progression Free Survival (PFS) is defined as the time from study start until disease progression or death. (NCT02158975)
Timeframe: 24 months after initiation of study treatment

Interventionmonths (Median)
MLN97083.2

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Objective Response Rate

The percentage of patients with an objective response rate will be determined. The overall response will be based on response in each compartment (skin, blood, lymph nodes and viscera) using a global composite scoring system. Objective response is considered (CR) Complete Response (Complete disappearance of all clinical evidence of disease), CRu (Complete Response Unconfirmed), or (PR) Partial Response (Regression of measurable disease). (NCT02158975)
Timeframe: Up to 24 months after initiation of study treatment

Interventionpercentage of patients (Number)
MLN97088

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Number Patients That Experience Adverse Events, Grades 3-5

To assess the safety and tolerability of MLN9708, the number of patients experiencing Adverse Events (AEs) greater than or equal to grade 3 will be recorded. (NCT02158975)
Timeframe: 30 days after the last dose of study drug

Interventionparticipants (Number)
AnemiaThrombocytopeniaDiarrheaMucocitisAcute Kidney InjuryAtrial FibrilationDyspneaHypercalcemiaHyponatremiaHypotensionLymph Node PainRashRespiratory FailureSupraventricular TachycardiaThromboembolic Event
MLN9708111111111111111

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Duration of Response

Time from documentation of tumor response to disease progression. (NCT02158975)
Timeframe: 24 months after initiation of study treatment

Interventionmonths (Number)
MLN970812

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Number of Participants With Incidence of Chronic Graft-versus-host Disease (cGVHD) After Receiving Allogeneic Stem Cell Transplant and Maintenance With MLN9708

Incidence of chronic Graft-versus-host disease GVHD was assessed based on the National Institutes of Health Consensus Development Project on Criteria for Clinical trials in Acute and Chronic Graft-versus-host-disease (Filipovich et al. 2005) from date of randomization until date of first documented progression, or date of death from any cause. (NCT02168101)
Timeframe: from date of enrollment every 28 days, up to 2 years

InterventionParticipants (Count of Participants)
MLN9708 - 2.3 mg2
MLN9708 - 3 mg2
MLN9708 - 4 mg2

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Median Overall Survival (OS) at 2 Years Post-allogeneic Stem Cell Transplant (ASCT)

Overall survival is measured as the interval from first study treatment until date of death, or date last known alive. (NCT02168101)
Timeframe: every 8 weeks for approximately 24 weeks after ASCT, then every 3 months thereafter for 2 years.

Interventionmonths (Median)
MLN9708 Combined Dose EscalationNA

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Number of Phase I Patients Receiving 2.3mg, 3mg, or 4mg MLN9708 Experiencing a Dose-Limiting Toxicity (DLT) to Determine the Maximum Tolerated Dose

The maximum tolerated dose (MTD) of MLN9708 will be determined as the dose at which ≤1 of 6 patients experiences a DLT during one cycle (28 days) of therapy utilizing the National Cancer Institute Common Technology Criteria for Adverse Events (NCI CTCAE) v4.0 (NCT02168101)
Timeframe: Collected from day of first dose to the end of the first treatment cycle, up to 28 days

InterventionParticipants (Count of Participants)
MLN9708 - 2.3 mg0
MLN9708 - 3 mg0
MLN9708 - 4 mg0

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Median Progression-Free Survival (PFS) at 2 Years Post-maintenance Therapy

PFS is measured from the date of first protocol treatment until date of disease progression or death occurs, or date of last adequate tumor assessment using the International Myeloma Working Group Uniform Response Criteria. IMWG disease progression is defined as an increase of ≥ 25% from the nadir in at least one of the following criteria: 1) serum M-protein, 2) urine M-protein, 3) only in patients with non-measurable serum and urine M-protein levels: difference in involved and uninvolved FLC levels, 4) Bone marrow plasma cell percentage (absolute % must be ≥10%). OR Disease progression also could include development of new lytic bone lesions or increase from baseline in size of lytic bone lesion(s); development of new soft tissue plasmacytoma(s) or definite increase from nadir in existing soft tissue plasmacytomas; or development of hypercalcemia (NCT02168101)
Timeframe: every 8 weeks for approximately 24 weeks then every 3 months thereafter for 2 years

Interventionmonths (Median)
MLN9708 Combined Dose Escalation6.5

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Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety of MLN9708 When Used as Maintenance After Allogeneic Stem Cell Transplant for Multiple Myeloma Multiple Myeloma

Defined as the number of participants with treatment-emergent grade 3/4/5 adverse events/serious adverse events utilizing the National Cancer Institute Common Technology Criteria for Adverse Events (NCI CTCAE) v4.0 determined to be related to MLN9708. (NCT02168101)
Timeframe: Defined as the time from Day 1 of study drug administration until 30 days after treatment completion for up to 2 years.

InterventionParticipants (Count of Participants)
MLN9708 - 2.3 mg1
MLN9708 - 3 mg2
MLN9708 - 4 mg2

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Number of Participants With Incidence of Acute Graft-versus-host Disease (aGVHD) After Receiving Allogeneic Stem Cell Transplant and Maintenance With MLN9708

Incidence of acute Graft-versus-host disease GVHD was assessed based on the National Institutes of Health Consensus Development Project on Criteria for Clinical trials in Acute and Chronic Graft-versus-host-disease (Przepiorka et al. 1995) from date of randomization until date of first documented progression, or date of death from any cause. (NCT02168101)
Timeframe: from date of enrollment every 28 days, up to 2 years

InterventionParticipants (Count of Participants)
MLN9708 - 2.3 mg2
MLN9708 - 3 mg2
MLN9708 - 4 mg2

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Time to Platelet Recovery Post Transplant

To measure the time to platelet recovery post-transplant (NCT02169791)
Timeframe: 1 year

Interventiondays (Median)
Haploidentical Transplant29

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Number of Participants Experiencing Relapse or Progression

To estimate the incidence of relapse/progression at one-year post-transplant. (NCT02169791)
Timeframe: 1 year

InterventionParticipants (Count of Participants)
Haploidentical Transplant10

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Neutrophil Engraftment

To obtain time to neutrophil engraftment post-transplant (NCT02169791)
Timeframe: 1 year

Interventiondays (Median)
Haploidentical Transplant16

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Graft Versus Host Disease

To measure days to onset of acute graft versus host disease (NCT02169791)
Timeframe: 100 days

Interventiondays (Median)
Haploidentical Transplant28.5

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Day 30 CD33 Donor Chimerism

To measure CD33 donor chimerism at Day 30 (NCT02169791)
Timeframe: 30 days

Interventionpercentage of chimerism (Median)
Haploidentical Transplant100

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Day 30 CD3 Donor Chimerism

To measure CD3 donor chimerism post-transplant (NCT02169791)
Timeframe: 30 days

Interventionpercentage of chimerism (Median)
Haploidentical Transplant100

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Change From Baseline in Complement Protein C3 and C4 at Day 84

(NCT02176486)
Timeframe: Baseline and Day 84

,,
Interventionmilligram per deciliter (mg/dL) (Mean)
Complement Protein C3: BaselineComplement Protein C3: Change at Day 84Complement Protein C4: BaselineComplement Protein C4: Change at Day 84
Cohort A: Ixazomib 0.5 mg82.2-7.412.4-0.8
Cohort B: Ixazomib 2 mg110.3-19.520.0-6.0
Pooled Placebo122.3-20.329.0-4.7

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Percentage of Participants Who Experienced at Least One AE Leading to Study Drug Discontinuation

(NCT02176486)
Timeframe: Baseline up to Day 168

Interventionpercentage of participants (Number)
Pooled Placebo0
Cohort A: Ixazomib 0.5 mg0
Cohort B: Ixazomib 2 mg0

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Percentage of Participants Who Experienced at Least One Grade Greater Than or Equal to (>=) 2 Treatment Emergent Adverse Event (TEAE)

(NCT02176486)
Timeframe: Baseline up to Day 101 (30 days after last dose of study drug)

Interventionpercentage of participants (Number)
Pooled Placebo33.3
Cohort A: Ixazomib 0.5 mg20.0
Cohort B: Ixazomib 2 mg25.0

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Percentage of Participants Who Experienced at Least One Treatment Emergent Serious Adverse Event (SAE)

(NCT02176486)
Timeframe: Baseline up to Day 101 (30 days after last dose of study drug)

Interventionpercentage of participants (Number)
Pooled Placebo0
Cohort A: Ixazomib 0.5 mg0
Cohort B: Ixazomib 2 mg0

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Percentage of Participants With at Least One Markedly Abnormal Value (MAV) for Hematologic Parameters

(NCT02176486)
Timeframe: Baseline up to Day 168

Interventionpercentage of participants (Number)
Pooled Placebo0
Cohort A: Ixazomib 0.5 mg0
Cohort B: Ixazomib 2 mg50.0

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Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Day 84

(NCT02176486)
Timeframe: Baseline and Day 84

,,
Interventionmilliliter/minute/1.73 square meter (Mean)
BaselineChange at Day 84
Cohort A: Ixazomib 0.5 mg130.02.6
Cohort B: Ixazomib 2 mg103.5-0.5
Pooled Placebo88.76.3

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Plasma Concentrations of Ixazomib at Each Scheduled Collection Time

(NCT02176486)
Timeframe: Cycle 1 Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose (Cycle length is equal to [=] 28 days)

,
Interventionnanogram per milliliter (ng/mL) (Mean)
Pre-dose0.25 hour0.5 hour1 hour1.5 hours2 hours4 hours8 hours24 hours168 hours
Cohort A: Ixazomib 0.5 mg0.00000.00000.42440.67760.50560.51340.10820.00000.00000.0000
Cohort B: Ixazomib 2 mg0.00000.00002.50332.20002.34002.27671.17000.99670.54930.0000

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Change From Baseline in Levels of Autoantibodies (Anti-double-stranded Deoxyribonucleic Acid [dsDNA]) at Day 84

(NCT02176486)
Timeframe: Baseline and Day 84

,,
Interventioninternational units/milliliter (IU/mL) (Mean)
BaselineChange at Day 84
Cohort A: Ixazomib 0.5 mg34.37.5
Cohort B: Ixazomib 2 mg129.39.5
Pooled Placebo18.7-4.3

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Change From Baseline in Urine Protein to Creatinine Ratio (UPCR) at Day 84

(NCT02176486)
Timeframe: Baseline and Day 84

,,
Interventionmilligram per milligram creatinine (Mean)
BaselineChange at Day 84
Cohort A: Ixazomib 0.5 mg2.6134-0.4740
Cohort B: Ixazomib 2 mg0.75350.9943
Pooled Placebo1.7567-0.1680

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Change From Baseline in Serum Creatinine (sCR) Level at Day 84

(NCT02176486)
Timeframe: Baseline and Day 84

,,
Interventionmicromoles per liter (mcmol/L) (Mean)
BaselineChange at Day 84
Cohort A: Ixazomib 0.5 mg72.4881.768
Cohort B: Ixazomib 2 mg81.77013.260
Pooled Placebo91.347-2.947

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Progression Free Survival (PFS)

PFS was defined as the time from the date of randomization to the date of first documentation of progressive disease (PD), as evaluated by an independent review committee according to International Myeloma Working Group (IMWG) criteria, or death due to any cause, whichever occured first. PD was defined as ≥25% increase from lowest value in: serum/urine M component; participants without measurable serum and urine M-protein levels, the difference between involved and uninvolved free light chain (FLC) levels must be >10 mg/dL; participants without measurable serum, urine M-protein levels and FLC levels, bone marrow plasma cell percent must have been ≥10%; new bone lesions/soft tissue plasmacytomas development/existing bone lesions/soft tissue plasmacytomas size increase; hypercalcemia development. (NCT02181413)
Timeframe: Randomization up to End of treatment (EOT) (24 months); thereafter followed up every 4 weeks until progression of disease or death (to data cutoff: approximately 4 years)

Interventionmonths (Median)
Placebo21.3
Ixazomib Citrate26.5

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Number of Participants Experiencing Dose-limiting Toxicity of MLN9708

A 3+3 design will be employed. At each dose, three patients will be initially evaluated. If no dose limiting toxicities are observed, the MLN9708 dose will be increased; if one dose limiting toxicity is observed, three additional patients will be treated at that dose. A dose at which two DLTs are observed in three or six patients are judged to be too toxic, the lower dose will be defined as the maximally tolerated dose (MTD). (NCT02250300)
Timeframe: 4 weeks

Interventiondose limiting toxicity (Number)
MLN9708 Phase I (3.0 mg)0
MLN9708 Phase I (4.0 mg)0

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Maximum-tolerated Dose of MLN9708.

Maximum-tolerated dose of ixazomib (MLN9708) will be determined from the incidence of dose limiting toxicities at each dosage. Results for both escalation phase cohorts (3.0 mg and 4.0 mg) were used to determine the maximum tolerated dose. (NCT02250300)
Timeframe: 4 weeks

Interventionmillligram (Number)
Maximum Tolerated Dose of Study Drug4

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Cumulative Incidence of Chronic Graft-versus-host Disease.

The number of participants who have graft-versus-host disease. The two expansion phase cohorts (3.0 mg and 4.0 mg) were not included in this analysis. (NCT02250300)
Timeframe: 1 year

InterventionParticipants (Count of Participants)
MLN9708 Phase II Matched Sibling9
MLN9708 Phase II Matched Unrelated10

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MRD-negative Rate After ASCT

For the purposes of this study, a patient will be considered as having minimal residual disease if a positive result (1x10E06) is obtained using the Adaptive Clonoseq MRD testing (NCT02253316)
Timeframe: Prior to beginning consolidation treatment (Day -28 to Day 0)

InterventionParticipants (Count of Participants)
Consolidation: Ixazomib, Lenalidomide, & Dexamethasone51

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Response Rate of IRD Consolidation

For the purposes of this study, response rate is defined as the improvement in complete response rate. Response will be determined by the International Myeloma Working Group (IMWG) Uniform Response Criteria. (NCT02253316)
Timeframe: After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment)

InterventionParticipants (Count of Participants)
Consolidation: Ixazomib, Lenalidomide, & Dexamethasone49

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Number of Participants With Improvement in Minimal Residual Disease (MRD)

For the purposes of this study, a patient will be considered as having minimal residual disease if a positive result (1x10E06) is obtained using the Adaptive Clonoseq MRD testing. (NCT02253316)
Timeframe: After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment)

InterventionParticipants (Count of Participants)
Consolidation: Ixazomib, Lenalidomide, & Dexamethasone19

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Compare Response Rate Between the Two Maintenance Arms

"Response will be determined by the International Myeloma Working Group (IMWG) Uniform Response Criteria. Response includes stringent complete response (sCR) and complete response (CR).~sCR requires all of the following:~CR as defined below~Normal free light chain ratio (0.26-1.65)~Absence of clonal cells in the bone marrow by immunohistochemistry or immunofluorescence~CR requires all of the following:~Disappearance of monoclonal protein by both protein electrophoresis and immunofixation studies from the blood and urine~If serum and urine monoclonal protein are unmeasurable, Normal free light chain ratio (0.26-1.65)~<5% plasma cells in the bone marrow~Disappearance of soft tissue plasmacytoma" (NCT02253316)
Timeframe: Through completion of maintenance treatment (estimated to be day 1095 of maintenance treatment)

InterventionParticipants (Count of Participants)
Maintenance Arm 1: Ixazomib50
Maintenance Arm 2: Lenalidomide80

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Toxicity of IRD Consolidation

For the purposes of this study, toxicity will be defined as inability to receive 4 cycles of IRD consolidation due to toxicity. (NCT02253316)
Timeframe: After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment)

InterventionParticipants (Count of Participants)
Consolidation: Ixazomib, Lenalidomide, & Dexamethasone7

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Rate of MRD-positive to MRD-negative Conversion Between the Two Maintenance Arms

(NCT02253316)
Timeframe: Cycle 13 Day 1 of maintenance treatment (Approximately Day 364 of maintenance treatment)

InterventionParticipants (Count of Participants)
Maintenance Arm 1: Ixazomib5
Maintenance Arm 2: Lenalidomide11

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Relapse-Free Survival (RFS)

RFS defined as interval from date of enrollment to date of first objective documentation of disease relapse or death from any cause. Survival or times to failure and time to progression functions estimated using Kaplan-Meier method. (NCT02302846)
Timeframe: 84 days

InterventionWeeks (Median)
Ixazomib34

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Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status

ECOG performance status assesses a participant's performance status on a 6-point scale ranging from 0=fully active/able to carry on all pre-disease activities without restriction; 1=restricted in physically strenuous activity, ambulatory/able to carry out light or sedentary work; 2=ambulatory (>50% of waking hours), capable of all self-care, unable to carry out any work activities; 3=capable of only limited self-care, confined to bed/chair >50% of waking hours; 4=completely disabled, cannot carry on any self-care, totally confined to bed/chair; 5=dead. Lower grades indicate improvement. (NCT02312258)
Timeframe: Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, and 26, progression free survival follow-up (PFSFU)- Visit 37 and progressive disease follow-up (PDFU)- Visit 26 (cycle length=28 days)

Interventionscore on a scale (Mean)
Cycle 2 Day 1Cycle 3 Day 1Cycle 4 Day 1Cycle 5 Day 1Cycle 6 Day 1Cycle 7 Day 1Cycle 8 Day 1Cycle 9 Day 1Cycle 10 Day 1Cycle 11 Day 1Cycle 12 Day 1Cycle 13 Day 1Cycle 14 Day 1Cycle 15 Day 1Cycle 16 Day 1Cycle 17 Day 1Cycle 18 Day 1Cycle 19 Day 1Cycle 20 Day 1Cycle 21 Day 1Cycle 22 Day 1Cycle 23 Day 1Cycle 24 Day 1Cycle 25 Day 1Cycle 26 Day 1
Placebo-0.0-0.0-0.0-0.0-0.0-0.0-0.1-0.1-0.1-0.1-0.1-0.00.0-0.0-0.0-0.00.00.00.00.00.10.00.10.00.0

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Time to Resolution of Peripheral Neuropathy (PN) Events

PN is defined as the event in the high-level term of peripheral neuropathies not elsewhere classified (NEC) according to the medical dictionary for regulatory activities (MedDRA). A PN event was considered as resolved if its final outcome was resolved with no subsequent PN event of the same preferred term occurring on the resolution date or the day before and after. Time to resolution was defined as the time from the initial onset date (inclusive) to the resolution date for resolved events. (NCT02312258)
Timeframe: Up to 52 months

Interventiondays (Median)
Placebo196.0
Ixazomib451.0

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Time to Progression (TTP)

TTP is defined as the time from the date of randomization to the date of first documentation of PD, using IMWG criteria. (NCT02312258)
Timeframe: From randomization until PD or death (up to 52 months)

Interventionmonths (Median)
Placebo9.6
Ixazomib17.8

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Time to Improvement of PN Events

PN is defined as the event in the high-level term of peripheral neuropathies NEC according to the MedDRA. A PN event was considered as resolved if its final outcome was resolved with no subsequent PN event of the same preferred term occurring on the improvement date or the day before and after. Time to improvement was defined as the time from the initial onset date (inclusive) to the improvement of event. (NCT02312258)
Timeframe: Up to 52 months

Interventiondays (Median)
Placebo81.0
Ixazomib64.0

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Time to End of the Next-line of Therapy After Study Treatment

Time to end of the next line of therapy is defined as the time from the date of randomization to the date of last dose of the next line of antineoplastic therapy following study treatment. (NCT02312258)
Timeframe: From randomization until PD or death (up to 52 months)

Interventionmonths (Median)
Placebo25.6
Ixazomib23.1

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Progression Free Survival 2 (PFS2)

PFS2 is defined as the time from the date of randomization to objective PD on next-line treatment using IMWG criteria, or death due to any cause, whichever occurred first. (NCT02312258)
Timeframe: From the date of randomization to every 12 weeks until second PD or death (up to 88 months)

Interventionmonths (Median)
Placebo50.3
Ixazomib51.3

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Progression Free Survival (PFS)

PFS is defined as the time from the date of randomization to the date of first documentation of progressive disease (PD) or death from any cause, as evaluated by an independent review committee (IRC) according to International Myeloma Working Group (IMWG) criteria, or death due to any cause, whichever occurs first. Per IMWG criteria, PD is defined as, increase of 25% of lowest response value in one or more of following criteria: serum M-component (absolute increase ≥0.5 g/ deciliter (dL)); or urine M-component (absolute increase ≥200 mg/24-hour); difference between involved and uninvolved free light chains (FLC) levels (absolute increase >10 mg/dL); or bone marrow plasma cell percentage (absolute plasma cell percentage ≥10%); development of new/ increase in size of existing bone lesions or soft tissue plasmacytoma; or development of hypercalcemia (corrected serum calcium >11.5mg/dL). (NCT02312258)
Timeframe: From randomization until PD or death (up to 52 months)

Interventionmonths (Median)
Placebo9.4
Ixazomib17.4

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PFS in a High-risk Population

High-risk population included but not be limited to participants carrying del17, t(4;14), t(14;16). PFS was defined as the time from the date of randomization to the date of first documentation of PD or death from any cause. (NCT02312258)
Timeframe: From randomization until PD or death (up to 52 months)

Interventionmonths (Median)
Placebo9.6
Ixazomib10.1

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Percentage of Participants With Conversion From Minimal Residual Disease (MRD) Positive to MRD Negative

Bone marrow aspirates and blood samples were sent to a central laboratory and were assessed for MRD using flow cytometry. MRD negativity was defined as absence of MRD and MRD positivity was defined as presence of MRD. MRD was assessed by 8-color flow cytometry with the IMWG recommended sensitivity of 10^-5. (NCT02312258)
Timeframe: Up to 52 months

Interventionpercentage of participants (Number)
Placebo3
Ixazomib6

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Percentage of Participants Who Develop a New Primary Malignancy

(NCT02312258)
Timeframe: From randomization until PD or death (up to 52 months)

Interventionpercentage of participants (Number)
Placebo6.2
Ixazomib5.2

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Overall Survival (OS)

OS was measured as the time from the date of randomization to the date of death. (NCT02312258)
Timeframe: From the date of randomization and every 12 weeks after PD on next-line therapy until death (up to 88 months)

Interventionmonths (Median)
Placebo69.5
Ixazomib64.8

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OS in a High-risk Population

High-risk population included but not be limited to participants carrying cytogenetic deletion (del)17, translocation [t](4;14), t(14;16). OS was measured as the time from the date of randomization to the date of death. (NCT02312258)
Timeframe: From the date of randomization and every 12 weeks after PD on next-line therapy until death (up to 88 months)

Interventionmonths (Median)
Placebo48.3
Ixazomib37.3

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Duration of Next-line Therapy

Duration of next-line therapy is defined as the time from the date of the first dose of the next line of antineoplastic therapy coming after study treatment to the date of the last dose. (NCT02312258)
Timeframe: From randomization until PD or death (up to 52 months)

Interventionmonths (Median)
Placebo14.0
Ixazomib8.7

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Percentage of Participants Who Achieve or Maintain Any Best Response Category During the Treatment Period

Response was assessed according to IMWG criteria based on IRC assessment. Best response included PR, VGPR and CR. PR= >=50% reduction of serum M protein and >=90% or <200 mg reduction urinary M protein in 24-hour, or >50% decrease in difference between involved and uninvolved FLC levels, or >50% reduction in bone marrow plasma cells, if bone marrow plasma cells >30% and >50% reduction in size of soft tissue plasmacytomas at baseline. VGPR= >90% reduction (<100 mg/24-hour) in serum M-protein + urine M-protein detectable by immunofixation but not on electrophoresis. Complete response= >5% plasma cells in myelogram with absence of paraprotein in serum and urine according to immunofixation. (NCT02312258)
Timeframe: Up to 27 months

,
Interventionpercentage of participants (Number)
PRVGPRCR
Ixazomib253431
Placebo293728

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Correlation of MRD Status With PFS and OS

PFS is defined as the time from the date of randomization to the date of first documentation of PD or death from any cause, as evaluated by an IRC according to IMWG criteria, or death due to any cause, whichever occurred first, assessed for up to 52 months in this outcome measure. OS was measured as the time from the date of randomization to the date of death, assessed for up to 52 months in this outcome measure. Participants with various types of known MRD status were pooled together for analysis of overall survival in this outcome measure. (NCT02312258)
Timeframe: From randomization up to 52 months

,
Interventionmonths (Median)
PFS for Participants with Known MRD+ at Study EntryPFS for Participants with Known MRD- at Study EntryOS for Participants with Known MRD Status (MRD- Status, MRD+ Status) at Study Entry
Ixazomib16.940.5NA
Placebo9.3NANA

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Correlation Between Frailty Status and PFS and OS

Participant's frailty status is classified as fit, unfit or frail on the bases of 4 components: age, the Charlson comorbidity scoring system without age weighting, the Katz index of independence in activities of daily living, and the Lawton instrumental activities of daily living scale. The sum of the 4 frailty scores equals the total frailty score. A total frailty score of 0 corresponds to a frailty status of fit; a total score of 1, to unfit; and a total score of 2 or more, to frail. PFS is defined as the time from the date of randomization to the date of first documentation of PD or death from any cause, as evaluated by an IRC according to IMWG criteria, or death due to any cause, whichever occurs first, assessed for up to 52 months in this outcome measure. OS will be measured as the time from the date of randomization to the date of death, assessed for up to 52 months in this outcome measure. (NCT02312258)
Timeframe: From randomization up to 52 months

,
Interventionmonths (Median)
PFS Based on Frailty Status of FitPFS Based on Frailty Status of UnfitPFS Based on Frailty Status of FrailOS Based on Frailty Status of FitOS Based on Frailty Status of UnfitOS Based on Frailty Status of Frail
Ixazomib18.617.615.4NANA46.5
Placebo8.510.611.1NANA42.5

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Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) as Measured by the Global Health Status (GHS)

"The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. The change from baseline in GHS (EORTC QLQ-C30) score is presented. Participant responses to the question How would you rate your overall health during the past week? are scored on a 7-point scale (1=very poor to 7=excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall GHS." (NCT02312258)
Timeframe: Baseline, Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, and 26 (cycle length=28 days)

,
Interventionscore on a scale (Mean)
Cycle 2Cycle 3Cycle 4Cycle 5Cycle 6Cycle 7Cycle 8Cycle 9Cycle 10Cycle 11Cycle 12Cycle 13Cycle 14Cycle 15Cycle 16Cycle 17Cycle 18Cycle 19Cycle 20Cycle 21Cycle 22Cycle 23Cycle 24Cycle 25Cycle 26
Ixazomib-0.1-1.2-0.60.6-1.5-0.7-0.40.1-1.60.20.3-0.5-1.1-0.70.5-0.21.71.10.41.31.00.92.30.30.9
Placebo1.72.11.51.81.03.10.91.42.03.93.94.23.12.22.52.40.51.61.11.51.62.1-0.30.02.8

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Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status

ECOG performance status assesses a participant's performance status on a 6-point scale ranging from 0=fully active/able to carry on all pre-disease activities without restriction; 1=restricted in physically strenuous activity, ambulatory/able to carry out light or sedentary work; 2=ambulatory (>50% of waking hours), capable of all self-care, unable to carry out any work activities; 3=capable of only limited self-care, confined to bed/chair >50% of waking hours; 4=completely disabled, cannot carry on any self-care, totally confined to bed/chair; 5=dead. Lower grades indicate improvement. (NCT02312258)
Timeframe: Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, and 26, progression free survival follow-up (PFSFU)- Visit 37 and progressive disease follow-up (PDFU)- Visit 26 (cycle length=28 days)

Interventionscore on a scale (Mean)
Cycle 2 Day 1Cycle 3 Day 1Cycle 4 Day 1Cycle 5 Day 1Cycle 6 Day 1Cycle 7 Day 1Cycle 8 Day 1Cycle 9 Day 1Cycle 10 Day 1Cycle 11 Day 1Cycle 12 Day 1Cycle 13 Day 1Cycle 14 Day 1Cycle 15 Day 1Cycle 16 Day 1Cycle 17 Day 1Cycle 18 Day 1Cycle 19 Day 1Cycle 20 Day 1Cycle 21 Day 1Cycle 22 Day 1Cycle 23 Day 1Cycle 24 Day 1Cycle 25 Day 1Cycle 26 Day 1PFSFU- Visit 37PDFU- Visit 26
Ixazomib-0.0-0.0-0.1-0.0-0.0-0.0-0.0-0.0-0.0-0.0-0.0-0.0-0.0-0.0-0.0-0.0-0.0-0.0-0.0-0.0-0.0-0.0-0.0-0.0-0.01.01.0

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Pharmacokinetic Parameter: Plasma Concentration of Ixazomib

Plasma concentrations of the complete hydrolysis product of ixazomib citrate (ixazomib) were measured using a validated liquid chromatography-tandem mass spectrometry (LC/MS/MS) assay. (NCT02312258)
Timeframe: Cycle 1 (1 and 4 hours post-dose Day 1, Days 8 and 15 pre-dose); Cycle 2 and 5 (Days 1 and 8 pre-dose) and Cycles 3, 4, 6 to 10 (Day 1 pre-dose) (cycle length=28 days)

Interventionnanogram per milliliter (ng/mL) (Geometric Mean)
Cycle 1 Day 1 - 1 Hour Post-doseCycle 1 Day 1 - 4 Hours Post-doseCycle 1 Day 8 - Pre-doseCycle 1 Day 15 - Pre-doseCycle 2 Day 1 - Pre-doseCycle 2 Day 8 - Pre-doseCycle 3 Day 1 - Pre-doseCycle 4 Day 1 - Pre-doseCycle 5 Day 1 - Pre-doseCycle 5 Day 8 - Pre-doseCycle 6 Day 1 - Pre-doseCycle 7 Day 1 - Pre-doseCycle 8 Day 1 - Pre-doseCycle 9 Day 1 - Pre-doseCycle 10 Day 1 - Pre-dose
Ixazomib19.35312.6981.6832.8281.9583.2172.2522.3632.3284.5472.5032.5852.6062.5662.686

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Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. TEAEs were defined as events that occurred after administration of the first dose of ixazomib or placebo through 30 days after the last dose of ixazomib or placebo. A SAE means any untoward medical occurrence that resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was considered medically significant. (NCT02312258)
Timeframe: First dose of study drug through 30 days after last dose of study drug (up to 88 months)

,
Interventionpercentage of participants (Number)
SAETEAE
Ixazomib2492
Placebo1782

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Time to Progression (TTP)

Duration of time from start of treatment to time of disease progression. (NCT02400437)
Timeframe: From start of treatment to time of disease progression, assessed up to 4 years after treatment start

Interventionmonths (Median)
Ixazomib, Dexamethasone, Rituximab33

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Progression-free Survival (PFS)

Duration of time from start of treatment to disease progression. Progressive disease is defined as occurring when a >25% increase in serum IgM and an absolute 500mg/dL increase in IgM level occurs from the lowest attained response value, or progression of clinically significant disease related symptoms. (NCT02400437)
Timeframe: From start of treatment to time of disease progression, assessed up to 4 years after treatment start

Interventionmonths (Median)
Ixazomib, Dexamethasone, Rituximab33

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Very Good Partial Response Rate (VGPR) for IDR

Rate of very good partial response or better in patients treated with IDR. VGPR is defined as a >90% reduction in serum IgM levels from baseline. (NCT02400437)
Timeframe: 76 weeks

InterventionParticipants (Count of Participants)
Ixazomib, Dexamethasone, Rituximab5

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Duration of Response (DOR)

The duration of response is measured from the time a participant achieved a response until the date of progression. (NCT02400437)
Timeframe: From the time each participant achieved a response to time of disease progression, assessed up to 4 years after treatment start

Interventionmonths (Median)
Ixazomib, Dexamethasone, Rituximab33

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Overall Response Rate

Overall response includes the rate of complete response (CR), partial response (PR), minimal response (MR), stabl disease (SD) and progressive disease (PD). Minor response is >25%-50% reduction in serum IgM from baseline. Partial Response is (>50-90% reduction in serum IgM from baseline. Very Good Partial Response is >90% reduction in serum IgM from baseline. Complete Response is resolution of all symptoms, normalization of serum IgM with disappearance of IgM paraprotein, resolution of any adenopathy or splenomegaly. (NCT02400437)
Timeframe: 2 Years

InterventionParticipants (Count of Participants)
Ixazomib, Dexamethasone, Rituximab25

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Overall Response Rate by MYD88 L265P and CXCR4-WHIM Status

To evaluate the overall response rate of participants by MYD88 L265P and CXCR4-WHIM mutations in WM. Overall response is defined as achieving at least a minor response, or >25% reduction in serum IgM from baseline. (NCT02400437)
Timeframe: 2 Years

InterventionParticipants (Count of Participants)
MYD88 Mutated, CXCR4 Wild-type11
MYD88 Mutated, CXCR4 Mutated14

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Evaluation of the Toxicities Associated With Ixazomib With Metronomic Cyclophosphamide and Dexamethasone.

(NCT02412228)
Timeframe: Assessed at baseline and end of study, up to 2 years, end of study reported

InterventionParticipants (Count of Participants)
Ixazomib Regimen12

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Evaluation of the Response Rate of Ixazomib With Metronomic Cyclophosphamide and Dexamethasone for First-line Treatment of Multiple Myeloma.

(NCT02412228)
Timeframe: Through study treatment completion, an average of 2 years

InterventionParticipants (Count of Participants)
Ixazomib Regimen12

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Percentage of Participants With Progression-Free Survival

The primary endpoint compares progression-free survival as a time to event endpoint from randomization between patients randomized to ixazomib and placebo maintenance in high risk multiple myeloma. Participants are considered a failure of the primary endpoint if they die or suffer from disease progression or if they initiate non-protocol anti-myeloma therapy. Disease progression was evaluated using the International Uniform Response Criteria. Participants must meet one of the criteria for disease progression specified in the protocol. The time to this event is the time from randomization to progression, death, or initiation of non-protocol anti myeloma therapy whichever comes first. The Kaplan-Meier estimator was used to estimate progression-free survival during the 2 year post-transplant follow-up period. Participants who were event-free at two years post-transplant are censored at that time. (NCT02440464)
Timeframe: 12 months and 21 months post-randomization

,
Interventionpercentage of participants (Number)
12 Months Post-randomization21 Months Post-randomization
Ixazomib Maintenance65.355.3
Placebo72.759.1

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Percentage of Participants With Infections Post-randomization by Time Point

All Grade 2 and 3 infections are reported according to the BMT CTN MOP (Manual of Procedures) where a higher grade corresponds to more severe symptoms. The cumulative incidence of severe, life-threatening, or fatal infections (Grade 3), treating death as a competing event, are estimated at 6, 12 and 18 months post randomization using Aalen-Johansen estimators for each treatment group. Comparison of cumulative incidence between the two treatment arms was done using a Z test at fixed time points. (NCT02440464)
Timeframe: 6, 12 and 18 months post-randomization

,
Interventionpercentage of participants (Number)
6 Months Post-randomization12 Months Post-randomization18 Months Post-randomization
Ixazomib Maintenance4.84.84.8
Placebo0.00.00.2

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Percentage of Participants With Infections Post-randomization by Infection Type

All Grade 2 and 3 infections are reported according to the BMT CTN MOP (Manual of Procedures) where a higher grade corresponds to more severe symptoms. The number of participants with post-randomization infections in each treatment arm is described by severity and type of infection. (NCT02440464)
Timeframe: 2 years post-randomization

,
InterventionParticipants (Count of Participants)
Participants with InfectionsMaximum Severity: Grade 2Maximum Severity: Grade 3Participants with Bacterial InfectionParticipants with Viral InfectionParticipants with Fungal InfectionParticipants with Other Infection
Ixazomib Maintenance8623601
Placebo1110121110

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Percentage of Participants With Best Response to Treatment After Randomization

Response was assessed using the International Uniform Response Criteria. Best response is the best of all the disease response status at each assessment time point after randomization. The order from best to worst is: Stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD). All disease classifications are relative to the patient's disease status prior to allogeneic transplant (i.e. study entry). This outcome was compared between treatment groups using all response data up to 2 years post-transplant. These response data were summarized separately for patients in sCR/CR at the time of randomization vs. those who were not in sCR/CR at the time of randomization. Within each group (in sCR/CR vs not in sCR/CR at randomization), best response to treatment was compared between treatment groups using a Fisher's Exact test instead of a chi-square test because of the small sample size. (NCT02440464)
Timeframe: 2 years post-transplant

InterventionParticipants (Count of Participants)
Participants in sCR/CR at Randomization72551676Participants in sCR/CR at Randomization72551677Participants Not in sCR/CR at Randomization72551677Participants Not in sCR/CR at Randomization72551676
Partial Response (PR)Stable Disease (SD)Progressive Disease (PD)Stringent Complete Response (sCR)Complete Response (CR)Very Good Partial Response (VGPR)
Ixazomib Maintenance6
Placebo5
Ixazomib Maintenance2
Ixazomib Maintenance0
Placebo0
Placebo1
Ixazomib Maintenance3
Placebo4
Placebo3
Ixazomib Maintenance4
Ixazomib Maintenance1

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Percentage of Participants With Overall Survival (OS)

Overall survival (OS) is defined as freedom from death from any cause. OS post-randomization is estimated for each arm using the Kaplan-Meier estimator and compared between arms using the log rank test. Participants who are alive at two years post-transplant are censored at that time. Confidence intervals for values of 100% were not calculated and are shown as 100%. (NCT02440464)
Timeframe: 12 months and 21 months post-randomization

,
Interventionpercentage of participants (Number)
12 Months Post-randomization21 Months Post-randomization
Ixazomib Maintenance100.094.7
Placebo90.986.4

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Percentage of Participants With Toxicities Post-randomization by Time Point

Toxicities are graded using NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0. Higher grades correspond to worse symptoms with the minimum grade being a 0 and the maximum grade being a 5. The cumulative incidence of Grade ≥ 3 toxicity was estimated at 6, 12 and 18 months post randomization using Aalen-Johansen estimators for each treatment group. Death from a cause other than toxicity was treated as a competing risk. Comparison of cumulative incidence between the two treatment arms was done using a Z test at fixed time points. (NCT02440464)
Timeframe: 6, 12 and 18 months post-randomization

,
Interventionpercentage of participants (Number)
6 Months Post-randomization12 Months Post-randomization18 Months Post-randomization
Ixazomib Maintenance57.161.961.9
Placebo63.668.272.7

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Percentage of Participants With Toxicities Post-randomization by Toxicity Type

Toxicities are graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0. Higher grades correspond to worse symptoms with the minimum grade being a 0 and the maximum grade being a 5. Toxicities post-randomization are described for each treatment arm by the type of toxicity as well as peak overall grade. (NCT02440464)
Timeframe: 2 years post-randomization

,
InterventionParticipants (Count of Participants)
Maximum Toxicity Grade : 0 - 2Maximum Toxicity Grade : 3Maximum Toxicity Grade : 4Maximum Toxicity Grade : 5Abnormal Liver SymptomsDysgeusiaEncephalopathyGrade 3-5 Allergic ReactionGrade 3-5 AnaphylaxisGrade 3-5 Blood/Lymphatic ToxicityGrade 3-5 Cardiac ToxicityGrade 3-5 FatigueGrade 3-5 FeverGrade 3-5 GI ToxicityGrade 3-5 Hearing LossGrade 3-5 HemorrhageGrade 3-5 Hepatobiliary/PancreasGrade 3-5 HyperthyroidismGrade 3-5 HypothyroidismGrade 3-5 Metabolic ToxicityGrade 3-5 Musculoskeletal ToxicityGrade 3-5 Nervous System ToxicityGrade 3-5 Ocular ToxicityGrade 3-5 Renal ToxicityGrade 3-5 Respiratory ToxicityGrade 3-5 Skin/Subcutaneous Tissue ToxicityGrade 3-5 Vascular ToxicityHepatitisIntestinal ObstructionLiver FailureSevere Muscle Weakness/ParalysisSudden Vision LossTumor Lysis Syndrome
Ixazomib Maintenance8130031000563060010041400212010001
Placebo6141122010873070070163425853100100

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Percentage of Participants With Response to Treatment

Response was assessed using the International Uniform Response Criteria. All disease classifications are relative to the patient's disease status prior to allogeneic transplant (i.e. study entry). Response to treatment after randomization (sCR, CR, VGPR, or PR) is summarized in each arm post-transplant at 18 months and 24 months post-transplant. These response data were summarized separately for patients in sCR/CR at the time of randomization vs. those who were not in sCR/CR at the time of randomization. (NCT02440464)
Timeframe: 18 months and 24 months post-transplant

InterventionParticipants (Count of Participants)
Response to Treatment at 18 Months Post-transplant for Participants in sCR/CR at Randomization72551676Response to Treatment at 18 Months Post-transplant for Participants in sCR/CR at Randomization72551677Response to Treatment at 18 Months Post-transplant for Participants Not in sCR/CR at Randomization72551676Response to Treatment at 18 Months Post-transplant for Participants Not in sCR/CR at Randomization72551677Response to Treatment at 24 Months Post-transplant for Participants in sCR/CR at Randomization72551676Response to Treatment at 24 Months Post-transplant for Participants in sCR/CR at Randomization72551677Response to Treatment at 24 Months Post-transplant for Participants Not in sCR/CR at Randomization72551677Response to Treatment at 24 Months Post-transplant for Participants Not in sCR/CR at Randomization72551676
Stringent Complete Response (sCR)Complete Response (CR)Very Good Partial Response (VGPR)Not EvaluablePartial Response (PR)Stable Disease (SD)Progressive Disease (PD)Died Before Evaluation
Ixazomib Maintenance3
Placebo3
Placebo2
Placebo0
Ixazomib Maintenance2
Placebo4
Ixazomib Maintenance4
Placebo1
Placebo6
Ixazomib Maintenance0
Ixazomib Maintenance1
Ixazomib Maintenance5

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Percentage of Participants With Chronic GVHD

Cumulative incidences of chronic GVHD were determined using the Aalen-Johansen estimator. Death prior to chronic GVHD is treated as the competing risk. Cumulative incidences are compared between treatment arms using Gray's test. Data of chronic GVHD were collected from providers and chart review according to the recommendations of the 2014 NIH Consensus Criteria. Eight organs are scored on a 0-3 scale to reflect degree of chronic GVHD involvement; 3 indicates the worst symptom. Liver and pulmonary function test results and use of systemic therapy for treatment of chronic GVHD are also recorded. (NCT02440464)
Timeframe: 12 months and 21 months post-randomization

,
Interventionpercentage of participants (Number)
12 Months Post-randomization21 Months Post-randomization
Ixazomib Maintenance68.668.6
Placebo63.663.6

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Medical Outcomes Study (MOS) - Short Form 36 (SF-36) Score

The MOS SF-36 instrument is a general assessment of health quality of life with eight components: Physical Functioning, Role Physical, Pain Index, General Health Perceptions, Vitality, Social Functioning, Role Emotional, and Mental Health Index. The scale is 0 to 100 where 0 is maximum disability and 100 is no disability, so the higher the score the more positive the outcome. The Physical Component Summary (PCS) and Mental Component Summary (MCS) were used as the outcome measures in summarizing the SF-36 data for this study. This self-reported questionnaire was completed at transplant, randomization, 6 months following the start of maintenance therapy (which corresponds to 6 months post-randomization), and 24 months post-transplant. Comparisons between treatment groups were performed prior to maintenance, 6 months post-randomization and at 24 months after transplant. Only English and Spanish speaking patients were eligible to participate in the quality of life component of this trial. (NCT02440464)
Timeframe: Randomization, 6 months post-randomization, 24 months post-transplant

,
Interventionscore on a scale (Median)
PCS: RandomizationPCS: 6 Months Post-randomizationPCS: 24 Months Post-transplantPCS: Change from Randomization to 6 Months Post-randomizationPCS: Change from Randomization to 24 Months Post-transplantMCS: RandomizationMCS: 6 Months Post-randomizationMCS: 24 Months Post-transplantMCS: Change from Randomization to 6 Months Post-randomizationMCS: Change from Randomization to 24 Months Post-transplant
Ixazomib Maintenance38.747.945.13.34.751.554.856.1-0.64.9
Placebo41.541.245.71.07.849.954.549.55.3-2.5

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Percentage of Participants With Acute GVHD (Grades III-IV)

Cumulative incidences of grade III-IV acute GVHD were determined using the Aalen-Johansen estimator. Death prior to acute GVHD is treated as the competing risk. Cumulative incidences are compared between treatment arms using Gray's test. Grading of acute GVHD was derived by consensus grading per BMT Clinical Trials Network (CTN) manual of procedures (MOP). The acute GVHD algorithm calculates the grade based on the organ (skin, GI and liver) stage and etiology/biopsy reported on the weekly GVHD form. Grade I aGVHD is defined as Skin stage of 1-2 and stage 0 for both GI and liver organs. Grade II aGVHD is stage 3 of skin, or stage 1 of GI, or stage 1 of liver. Grade III is stage 2-4 for GI, or stage 2-3 of liver. Grade IV is stage 4 of skin, or stage 4 of liver. Grade 4 is the worst outcome. (NCT02440464)
Timeframe: 100 days post-randomization

Interventionpercentage of participants (Number)
Ixazomib Maintenance9.5
Placebo0.0

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Percentage of Participants With Disease Progression

Disease progression was evaluated using the International Uniform Response Criteria. Participants in sCR/CR must meet at least one of the criteria for disease progression specified in the protocol for sCR/CR participants; those not in sCR/CR must meet at least one of the disease progression criteria specified in the protocol for those not in sCR/CR. The cumulative incidence of progression from randomization will be estimated for each treatment arm using the Aalen-Johansen estimator, with death in remission treated as a competing risk. Initiation of anti-myeloma therapy will be considered evidence of progression. Participants who were event-free at two years post-transplant are censored at that time. (NCT02440464)
Timeframe: 12 months and 21 months post-randomization

,
Interventionpercentage of participants (Number)
12 Months Post-randomization21 Months Post-randomization
Ixazomib Maintenance34.744.7
Placebo27.336.4

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Functional Assessment of Cancer Therapy (FACT) - Bone Marrow Transplant (BMT) Total Score

The FACT-BMT version 4.0 instrument is comprised of the Functional Assessment of Cancer Therapy - General (FACT-G), which evaluates the health-related quality of life (HQL) of patients receiving treatment for cancer, and the BMT Concerns module, that addresses disease and treatment-related questions specific to bone marrow transplant. This scale goes from 0 to 196 where higher scores indicate better functioning. The FACT-BMT Total, which has all items in the FACT-G and BMT modules, was used as the outcome measure. This self-reported questionnaire was completed at transplant, randomization, 6 months following the start of maintenance therapy (which corresponds to 6 months post-randomization), and 24 months post-transplant. Comparisons between treatment groups were performed prior to maintenance, 6 months post-randomization and at 24 months after transplant. Only English and Spanish speaking patients were eligible to participate in the quality of life component of this trial. (NCT02440464)
Timeframe: Randomization, 6-months post-randomization, 24 months post-transplant

,
Interventionscore on a scale (Median)
Randomization6 Months Post-randomization24 Months Post-transplantChange from Randomization to 6 Months Post-randomizationChange from Randomization to 24 Months Post-transplant
Ixazomib Maintenance100.0121.4121.55.012.6
Placebo110.0114.0109.07.03.0

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Overall Survival (OS)

Overall survival was determined as the average number of months subjects survived following enrollment. (NCT02477215)
Timeframe: 36 months

InterventionMONTHS (Median)
MLN9708, Bendamustine and Dexamethasone23.2

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Progression Free Survival (PFS)

This measure is the number of months participants remain free from evidence of disease. (NCT02477215)
Timeframe: 18 months

InterventionMONTHS (Median)
MLN9708, Bendamustine and Dexamethasone5.2

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Cumulative Response Rates in Patients After Eight Cycles.

Percentage of subject response rates at any point during the eight cycles. (NCT02477215)
Timeframe: 18 months

Interventionpercentage of participants (Number)
MLN9708, Bendamustine and Dexamethasone28

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Duration of Response (DoR)

Median time in months participants maintain CR, PR or stable disease. (NCT02477215)
Timeframe: 36 months

InterventionMONTHS (Median)
MLN9708, Bendamustine and Dexamethasone5.1

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Maximum Tolerated Dose of Bendamustine

Maximum tolerated dose of bendamustine in combination with fixed doses of ixazomib (MLN9708) and dexamethasone will be determined from the incidence of dose limiting toxicities at each dosage. (NCT02477215)
Timeframe: Six months for each dosing cohort

Interventionmg/m^2 (Number)
MLN9708, Bendamustine and Dexamethasone80

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Number of Participants Experiencing Dose-Limiting Toxicity (DLT)

A 3+3 design was employed. At each dose, three patients were initially evaluated. If no dose limiting toxicities were observed, the bendamustine dose was increased; if one dose limiting toxicity is observed, three additional patients were treated at that dose. A dose at which 2 DLTs were observed in 3 or 6 patients were judged to be too toxic and the lower dose was defined as the maximally tolerated dose (MTD). (NCT02477215)
Timeframe: Six months

InterventionParticipants (Count of Participants)
Bendamustine (70 mg/m^2), MLN9708, Dexamethasone0
Bendamustine (80 mg/m^2), MLN9708, Dexamethasone1
Bendamustine (90 mg/m^2), MLN9708, Dexamethasone2

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Objective Response Rate

Objective response rate was defined as the number of subjects achieving a complete response (CR) or partial response (PR) after at least four cycles of ixazomib (MLN9708) and bendamustine plus dexamethasone. (NCT02477215)
Timeframe: 18 months

Interventionparticipants (Number)
MLN9708, Bendamustine and Dexamethasone11

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12-month PFS (Progression Free Survival) of Treatment With Ixazomib in Combination With DA-EPOCH-R (Phase II)

12-month PFS will be defined as the percentage of patients alive and progression free 12 months from start of therapy. Patients lost to follow up will be censored from last point of contact. PFS was calculated using a Kplan-meier estimation with the probability of patients being progression free at 12 months, presented as the percentage based on this probability. (NCT02481310)
Timeframe: Up to 12 months from initiation of treatment

Interventionprobability (%) of patients alive (Number)
Treatment (Combination Chemotherapy, Rituximab, Ixazomib)75.84

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Change in Serum Osteocalcin From Baseline to End of Study in Patients With Relapsed/Refractory Multiple Myeloma.

To evaluate the effect of Ixazomib on inducing osteoblast activation as measured by change in serum osteocalcin from baseline to end of study in patients with relapsed/refractory multiple myeloma. (NCT02499081)
Timeframe: Baseline, Treatment (28-day cycles for 6 cycles)

Interventionng/ML (Median)
Ixazomib20.00

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Incidence of Discontinuation of All Systemic Immune Suppressive Therapies

The incidence of complete discontinuation of all systemic immune-suppressive therapies will be determined at 1 year. (NCT02513498)
Timeframe: 1 year

InterventionParticipants (Count of Participants)
Treatment (Ixazomib Citrate)0

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Biologic Studies

The biologic impact of proteasome inhibition in the treatment of chronic GVHD will be assessed. (NCT02513498)
Timeframe: Up to 6 months

InterventionParticipants (Count of Participants)
Treatment (Ixazomib Citrate)0

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Cumulative Incidence of Primary Malignancy Relapse

Defined as hematologic relapse or any unplanned intervention to prevent progression of disease in patients with evidence (molecular, cytogenetic, flow cytometric, radiographic) of malignant disease after transplantation. (NCT02513498)
Timeframe: 1 year

InterventionParticipants (Count of Participants)
Treatment (Ixazomib Citrate)1

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Probability of Failure-free Survival at 1 Year

Kaplan-Meier estimate assessed at 1 year for failure-free survival, defined as the absence of death from any cause, relapse or addition of secondary immune suppressive agents. (NCT02513498)
Timeframe: 1 year

Interventionprobability of failure-free survival (Number)
Treatment (Ixazomib Citrate)0.57

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Probability of Non-relapse Mortality at 1 Year

Kaplan-Meier estimate assessed at 1 year for probability of non-relapse mortality, defined as death in the absence of primary malignancy relapse after transplant. (NCT02513498)
Timeframe: 1 year

Interventionnon-relapse mortality probability (Number)
Treatment (Ixazomib Citrate)0.1

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Probability of Overall Survival at 1 Year

Kaplan-Meier estimate assessed at 1 year for overall survival, defined as absence of death from any cause. (NCT02513498)
Timeframe: 1 year

Interventionprobability of overall survival (Number)
Treatment (Ixazomib Citrate).9

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Probability of Treatment Failure at 6 Months

Kaplan-Meier estimate assessed at 6 months for probability of treatment failure, defined as addition of a line of systemic immune-suppressive therapy, recurrent malignancy, or death. (NCT02513498)
Timeframe: 6 months

InterventionTreatment failure probability (Number)
Treatment (Ixazomib Citrate).28

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Treatment Success

Treatment success will be estimated at 1 year with a composite outcome of complete resolution of all reversible chronic graft-versus-host disease (GVHD) manifestations, discontinuation of all systemic immune suppressive agents, and freedom from death or primary malignancy relapse after transplant. (NCT02513498)
Timeframe: 1 year

InterventionParticipants (Count of Participants)
Treatment (Ixazomib Citrate)0

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Use of Additional Systemic Immune Suppressive Therapies

Addition of therapy after ixazomib constitutes failure, could occur at any time from baseline to 12mo. (NCT02513498)
Timeframe: 1 year

InterventionParticipants (Count of Participants)
Treatment (Ixazomib Citrate)21

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Incidence of Adverse Events

According to National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCT02513498)
Timeframe: Up to 30 days following completion of study treatment

Interventionparticipants (Number)
Serious Adverse EventsNon-Serious Adverse Events
Treatment (Ixazomib Citrate)1918

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Overall Response Rate (ORR) (Complete Response + Partial Response)

ORR at 6 months will be determined by both clinician-defined categories of complete response and partial response, as well as separately calculated according to the proposed response definitions of the NIH Consensus Conference. (NCT02513498)
Timeframe: 6 months

Interventionparticipants (Number)
Physician impression ORRNIH ORR
Treatment (Ixazomib Citrate)1617

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Symptoms as Measured by Patient Self-report--Lee Chronic GVHD Symptom Scale

Lee symptom scale (LSS) has subscales with min=0, max=100; results given are 12mo scores, with higher numbers indicating higher symptom burden. (NCT02513498)
Timeframe: 1 year

Interventionunits on a scale (Median)
skin scaleenergy scalelung scaleeye scalenutrition scalepsychological scalemouth scaleoverall summary score
Treatment (Ixazomib Citrate)15251050016.7020.8

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Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36)

SF-36 subscales have min=0 and max=100; results given are actual scores at 12mo, with higher scores indicating higher quality of life. (NCT02513498)
Timeframe: 1 year

Interventionunits on a scale (Median)
norm-based physical functioningnorm-based role-physical scorenorm-based bodily pain scorenorm-based general health scorenorm-based vitality scorenorm-based social functioning scorenorm-based role-emotional scorenorm-based mental health scorestandardized physical component scorestandardized mental component score
Treatment (Ixazomib Citrate)44.437.346.136.24951.448.152.839.753.8

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Symptoms as Measured by Patient Self-report--Functional Assessment of Chronic Illness Therapy (FACT)

"FACT-BMT subscales have various min/max, see below; results given are actual 12mo scores, with higher scores indicating better functioning.~FACT physical well-being (0-28) FACT social/family well-being (0-28) FACT emotional well-being (0-24) FACT functional well-being (0-28) FACT Bone Marrow Transplant (BMT) subscale (0-40) FACT trial outcome index (0-96) FACT-General (G) (0-108) FACT-BMT total (0-148)" (NCT02513498)
Timeframe: 1 year

Interventionunits on a scale (Median)
physical well-beingsocial/family well-beingemotional well-beingfunctional well-beingBMT subscaleFACT-Gtrial outcome indexFACT-BMT total
Treatment (Ixazomib Citrate)2323.721183284.772114.1

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Symptoms as Measured by Patient Self-report--Human Activities Profile (HAP)

"HAP subscales have min=0 and max=94; results given are actual 12mo scores, with higher scores indicating better functioning.~Maximum Activity Score (MAS) is highest item number answered still doing. Represents highest oxygen demanding activity that respondent still performs.~Adjusted Activity Score (AAS) is MAS minus total number of stopped doing responses below MAS. A measure of usual daily activities.~Modified AAS is MAS minus total number of stopped doing responses below MAS but not penalized for not doing activities not permitted post transplant. The following items are not counted against the score:11,15,19,20,22,25,34,41,42,47,49,50,52,53,54,57,72,73,77,78." (NCT02513498)
Timeframe: 1 year

Interventionunits on a scale (Median)
maximum activity scoreadjusted activity scoremodified adjusted activity score
Treatment (Ixazomib Citrate)747070

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Extramedullary Response Rate

Extramedullary response, defined as a response by extramedullary plasmacytoma or plasma cell count parameters. The extramedullary response rate will be estimated by the number of responders(patients that achieved a partial or complete response) divided by the number of evaluable patients. Exact binomial confidence intervals will be calculated. (NCT02547662)
Timeframe: 4 years

Interventionproportion of participants (Number)
Treatment (Ixazomib Citrate, Pomalidomide, Dexamethasone)0.40

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Confirmed Response Rate

A confirmed response is defined as a patient who has achieved a stringent complete response (sCR), complete response (CR), very good partial response (PR), or PR on two consecutive evaluations. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. (NCT02547662)
Timeframe: 4 years

Interventionproportion of patients (Number)
Treatment (Ixazomib Citrate, Pomalidomide, Dexamethasone)0.06

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Incidence of Adverse Events Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0

Number of patients with adverse events is reported here, the full list of those adverse events and their frequency is reported in the adverse event section. (NCT02547662)
Timeframe: 4 years 1 month

InterventionParticipants (Count of Participants)
Treatment (Ixazomib Citrate, Pomalidomide, Dexamethasone)17

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Biochemical Response Rate

The biochemical response rate will be estimated by the number of responders(patients that achieved partial or complete response) divided by the number of evaluable patients who have measurable disease by serum M-protein, urine M-protein, or serum FLC assay at baseline. Exact binomial confidence intervals will be calculated. (NCT02547662)
Timeframe: 4 years

Interventionproportion of participants (Number)
Treatment (Ixazomib Citrate, Pomalidomide, Dexamethasone)0.25

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Progression-free Survival

The distribution of progression-free survival will be estimated using the method of Kaplan-Meier. (NCT02547662)
Timeframe: 4 years 8 months

InterventionMonths (Median)
Treatment (Ixazomib Citrate, Pomalidomide, Dexamethasone)4.5

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Number of Participants With Adverse Events, Graded According to CTCAE Version 4.0

Adverse events Toxicity during the 24 months plus one month of post autologous transplant maintenance therapy (NCT02619682)
Timeframe: 2 years plus one month

InterventionParticipants (Count of Participants)
Post Autologous Transplant Maintenance30

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Overall Survival

all MM patients who got post autologous transplant study therapy (NCT02619682)
Timeframe: Median 4.6 years from start of therapy

InterventionParticipants (Count of Participants)
Post Autologous Transplant Maintenance21

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Disease Free Survival

(NCT02619682)
Timeframe: Median of 4.6 years from start of study therapy

InterventionParticipants (Count of Participants)
Post Autologous Transplant Maintenance11

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Number of Patients With Safety and Tolerability of Ixazomib

Safety was assessed with routine postoperative laboratory, vital sign, neurologic exam, and imaging studies through the day of surgery to staple or suture removal. This data was collected and any adverse events graded and their relationship to ixazomib administration determined. (NCT02630030)
Timeframe: At the time of surgery, approximately 3 hours

InterventionParticipants (Count of Participants)
Ixazomib3

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Number of Participants With Treatment-Emergent Adverse Events

The National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (NCI CTCAE) was used to stratify any adverse patient response to ixazomib. There were no clinically relevant adverse events as a result of ixazomib administration. (NCT02630030)
Timeframe: Up to 30 days

InterventionParticipants (Count of Participants)
Ixazomib3

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Concentration of Ixazomib in Tumor Tissue

The relationship between patient's demographic, tumor and drug concentration results will be assessed with Pearson's correlation coefficient and tested with Wald's test. In addition, the mean and standard error of the concentrations will be estimated using a random-effects model to account for the within-patient correlation of the tumor biopsy samples. Given the limited number of observations, a relatively simple covariance matrix (e.g. compound symmetry) will be assumed. (NCT02630030)
Timeframe: At time of surgery, approximately 3 hours

Interventionng/g (Number)ng/g (Number)
Participant 3 Sample 1Participant 3 Sample 2Participant 3 Sample 3Participant 1Participant 2Participant 3
Ixazomib7.882.034.172.703.2521.818.036.2

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Incidence of Adverse Events Graded According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 (Phase II)

The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. (NCT02633059)
Timeframe: Up to 6 months

InterventionParticipants (Count of Participants)
Grade 3+ Adverse Events, Regardless of AttributionGrade 3+ Adverse Events, At Least Possibly RelatedGrade 4+ Adverse Events, Regardless of AttributionGrade 4+ Adverse Events, At Least Possibly RelatedGrade 5 Adverse Events, Regardless of AttributionGrade 5 Adverse Events, At Least Possibly RelatedGrade 3+ Heme Adverse Events, Regardless of AttributionGrade 3+ Heme Adverse Events, At Least Possibly RelatedGrade 4+ Heme Adverse Events, Regardless of AttributionGrade 4+ Heme Adverse Events, At Least Possibly RelatedGrade 5 Heme Adverse Events, Regardless of AttributionGrade 5 Heme Adverse Events, At Least Possibly RelatedGrade 3+ Non-heme Adverse Events, Regardless of AttributionGrade 3+ Non-heme Adverse Events, At Least Possibly RelatedGrade 4+ Non-heme Adverse Events, Regardless of AttributionGrade 4+ Non-heme Adverse Events, At Least Possibly RelatedGrade 5 Non-heme Adverse Events, Regardless of AttributionGrade 5 Non-heme Adverse Events, At Least Possibly Related
Phase 2: Dose Level 114131092013139900534220

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Overall Survival (Phase II)

The distribution of overall survival will be estimated using the method of Kaplan-Meier. (NCT02633059)
Timeframe: Up to 3 years

Interventionmonths (Median)
Phase II and MTD21.0

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Progression Free Survival (Phase II)

The distribution of progression-free survival will be estimated using the method of Kaplan-Meier. (NCT02633059)
Timeframe: Up to 3 years

Interventionmonths (Median)
Phase II and MTD3.8

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Rate of Complete Response (CR) (Phase II)

The rate of CR will be estimated by the number of patients with a sCR or CR or divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportions will be calculated. (NCT02633059)
Timeframe: Up to 6 months

InterventionParticipants (Count of Participants)
Phase II and MTD0

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Rate of Partial Response (PR) (Phase II)

The rate of PR will be estimated by the number of patients with a VGPR or PR divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportions will be calculated. (NCT02633059)
Timeframe: Up to 6 months

InterventionParticipants (Count of Participants)
Phase II and MTD2

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Rate of Confirmed Response, Defined as a Patient Who Has Achieved a Stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR), or Partial Response (PR) on Two Consecutive Evaluations (Phase II)

Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportion will be calculated. (NCT02633059)
Timeframe: Up to 6 months

InterventionParticipants (Count of Participants)
PRSDNACRVGPRsCR
Phase II and MTD2614000

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The Number of Participants Who Experienced Dose Limiting Toxicities. Maximum Tolerated Dose (MTD) of Ixazomib Citrate and Idasanutlin in Combination With Dexamethasone (Phase I)

Defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients (at least 2 of a maximum of 6 new patients). DLT is graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. (NCT02633059)
Timeframe: 28 days

InterventionParticipants (Count of Participants)
Phase 1: Dose Level 00
Phase 1: Dose Level 10
Phase 1: Dose Level 22
Phase 2: Dose Level 11

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Incidence of Adverse Events Graded According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 (Phase I)

Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses. (NCT02633059)
Timeframe: 30 days after the last dose of study treatment, up to 3 years

,,
InterventionParticipants (Count of Participants)
Grade 3+ Adverse Events, Regardless of AttributionGrade 3+ Adverse Events, At Least Possibly RelatedGrade 4+ Adverse Events, Regardless of AttributionGrade 4+ Adverse Events, At Least Possibly RelatedGrade 5 Adverse Events, Regardless of AttributionGrade 5 Adverse Events, At Least Possibly RelatedGrade 3+ Heme Adverse Events, Regardless of AttributionGrade 3+ Heme Adverse Events, At Least Possibly RelatedGrade 4+ Heme Adverse Events, Regardless of AttributionGrade 4+ Heme Adverse Events, At Least Possibly RelatedGrade 5 Heme Adverse Events, Regardless of AttributionGrade 5 Heme Adverse Events, At Least Possibly RelatedGrade 3+ Non-heme Adverse Events, Regardless of AttributionGrade 3+ Non-heme Adverse Events, At Least Possibly RelatedGrade 4+ Non-heme Adverse Events, Regardless of AttributionGrade 4+ Non-heme Adverse Events, At Least Possibly RelatedGrade 5 Non-heme Adverse Events, Regardless of AttributionGrade 5 Non-heme Adverse Events, At Least Possibly Related
Phase 1: Dose Level 0320000320000110000
Phase 1: Dose Level 1441100441100210000
Phase 1: Dose Level 2333200333200000000

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Duration of Response

"Duration of overall response: The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).~The duration of overall CR is measured from the time measurement criteria are first met for CR until the first date that progressive disease is objectively documented." (NCT02898259)
Timeframe: Up to 15 months after beginning treatment

Interventionmonths (Median)
DL1 (Ixazomib 2.0 mg + Lenalidomide 20 mg + Rituximab 375mg/m2)2.7
DL2 (Ixazomib 3.0 mg + Lenalidomide 20 mg + Rituximab 375mg/m2)8.9
DL3/MTD (Ixazomib 4.0 mg + Lenalidomide 20 mg + Rituximab 375mg/m2)5.5
Expansion Cohort I: Follicular Lymphoma at MTD8.7

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Maximum Tolerated Dose (MTD) of Oral Ixazomib

"To determine the MTD of the combination of oral ixazomib and lenalidomide plus rituximab in patients with previously untreated low-grade B cell lymphoma having high tumor burden by GELF criteria or FLIPI 3-5.~MTD will be determined using the first 12 participants 15 months after beginning treatment" (NCT02898259)
Timeframe: 15 months after beginning treatment

Interventionmg (Number)
Lenalidomide + Ixazomib + Rituximab4

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Overall Response Rate

These criteria are based on the Revised Response Criteria for Malignant Lymphoma and include the following categories: Complete Response (CR)(Complete disappearance of all detectable clinical evidence of disease, and disease-related symptoms if present prior to therapy), Partial Response (PR) (A ≥ 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or extranodal masses), Stable Disease (SD) (Failing to attain the criteria needed for a PR or CR, but not fulfilling those for progressive disease), Relapse and Progression (PD) (For determination of relapsed and progressive disease, lymph nodes should be considered abnormal if the long axis is more than 1.5 cm, regardless of the short axis). (NCT02898259)
Timeframe: Up to 15 months after beginning treatment

,,,,
InterventionParticipants (Count of Participants)
Complete responseStable DiseasePartial ResponseRelapse and Progression
DL1 (Ixazomib 2.0 mg + Lenalidomide 20 mg + Rituximab 375mg/m2)1200
DL2 (Ixazomib 3.0 mg + Lenalidomide 20 mg + Rituximab 375mg/m2)2001
DL3/MTD (Ixazomib 4.0 mg + Lenalidomide 20 mg + Rituximab 375mg/m2)2311
Expansion Cohort 2: Non-Follicular Lymphoma at MTD0000
Expansion Cohort I: Follicular Lymphoma at MTD5000

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Time to Treatment Failure

Time to treatment failure (event-free survival) is defined as the time from study entry to first event of disease progression, discontinuation of treatment for any reason, initiation of new treatment, or death. (NCT02898259)
Timeframe: Up to 15 months after beginning treatment

Interventionmonths (Median)
DL1 (Ixazomib 2.0 mg + Lenalidomide 20 mg + Rituximab 375mg/m2)10
DL2 (Ixazomib 3.0 mg + Lenalidomide 20 mg + Rituximab 375mg/m2)0
DL3/MTD (Ixazomib 4.0 mg + Lenalidomide 20 mg + Rituximab 375mg/m2)6.1
Expansion Cohort I: Follicular Lymphoma at MTD5.8

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Time to Progression

Duration of time from start of treatment to time of progression. (NCT02898259)
Timeframe: Up to 15 months after beginning treatment

Interventionmonths (Median)
DL1 (Ixazomib 2.0 mg + Lenalidomide 20 mg + Rituximab 375mg/m2)0
DL2 (Ixazomib 3.0 mg + Lenalidomide 20 mg + Rituximab 375mg/m2)2.5
DL3/MTD (Ixazomib 4.0 mg + Lenalidomide 20 mg + Rituximab 375mg/m2)9.0
Expansion Cohort I: Follicular Lymphoma at MTD4.6

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Progression Free Survival

"A number of participants who survived without disease progression~PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.~Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions." (NCT02898259)
Timeframe: Up to 15 months after beginning treatment

InterventionParticipants (Count of Participants)
DL1 (Ixazomib 2.0 mg + Lenalidomide 20 mg + Rituximab 375mg/m2)3
DL2 (Ixazomib 3.0 mg + Lenalidomide 20 mg + Rituximab 375mg/m2)2
DL3/MTD (Ixazomib 4.0 mg + Lenalidomide 20 mg + Rituximab 375mg/m2)5
Expansion Cohort I: Follicular Lymphoma at MTD5
Expansion Cohort 2: Non-Follicular Lymphoma at MTD0

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Overall Survival

Overall survival is defined as the date of study entry to the date of death. (NCT02898259)
Timeframe: Up to 15 months after beginning treatment

InterventionParticipants (Count of Participants)
DL1 (Ixazomib 2.0 mg + Lenalidomide 20 mg + Rituximab 375mg/m2)3
DL2 (Ixazomib 3.0 mg + Lenalidomide 20 mg + Rituximab 375mg/m2)3
DL3/MTD (Ixazomib 4.0 mg + Lenalidomide 20 mg + Rituximab 375mg/m2)6
Expansion Cohort I: Follicular Lymphoma at MTD5
Expansion Cohort 2: Non-Follicular Lymphoma at MTD0

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Time to Progression (TTP)

TTP was measured as the time in months from the first dose of study treatment to the date of the first documented PD as assessed using IMWG criteria. PD required one of the following: increase of ≥ 25% from nadir in: serum M-component (absolute increase ≥ 0.5 g/dL); urine M-component (absolute increase ≥ 200 mg/24 hours); in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels (absolute increase > 10 mg/dL); development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia (corrected serum calcium > 11.5 mg/dL) attributed solely to plasma cell proliferative disease. (NCT02917941)
Timeframe: Up to approximately 33 months

Interventionmonths (Median)
Ixazomib 4 mg + Lenalidomide 25 mg + Dexamethasone 40 mg22.57

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Progression-free Survival (PFS)

PFS was defined as the time in months from the date of first study drug administration to the date of first documentation of PD or death from any cause, whichever occurred first. PD required one of the following: increase of ≥ 25% from nadir in: serum M-component (absolute increase ≥ 0.5 g/dl); urine M-component (absolute increase ≥ 200 mg/24 hours); in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved free light chain (FLC) levels (absolute increase > 10 mg/dl); development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia (corrected serum calcium > 11.5 mg/dl) attributed solely to plasma cell proliferative disease. (NCT02917941)
Timeframe: Up to approximately 33 months

Interventionmonths (Median)
Ixazomib 4 mg + Lenalidomide 25 mg + Dexamethasone 40 mg22.05

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Percentage of Participants With Very Good Partial Response (VGPR) or Better Response (Complete Response (CR) + VGPR)

Response was assessed using International Myeloma Working Group (IMWG) Criteria. CR was defined as negative immunofixation in serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. VGPR was defined as serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hours. (NCT02917941)
Timeframe: Up to approximately 33 months

Interventionpercentage of participants (Number)
Ixazomib 4 mg + Lenalidomide 25 mg + Dexamethasone 40 mg50.0

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Overall Survival (OS)

OS was defined as the time from the date of first study drug administration to the date of death. (NCT02917941)
Timeframe: Up to approximately 33 months

Interventionmonths (Median)
Ixazomib 4 mg + Lenalidomide 25 mg + Dexamethasone 40 mgNA

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Overall Response Rate (ORR)

ORR:percentage of participants with CR including stringent complete response(sCR),VGPR,partial response(PR) per independent review committee(IRC)by IMWG criteria.CR: serum,urine -ve immunofixation; disappearance of soft tissue plasmacytomas,<5%plasma cells in bone marrow(CR in those with only measurable disease by serum FLC levels=normal FLC ratio 0.26 to 1.65+CR criteria).sCR:CR+normal FLC ratio,absence of clonal plasma cells(immunohistochemistry)or 2-to 4-color flow cytometry.VGPR:serum,urine M-protein detectable by immunofixation,not by electrophoresis or ≥90%reduction,<100mg/24hrs(VGPR in those with only measurable disease by serum FLC levels,requires>90%decrease in involved-uninvolved FLC level difference).PR: ≥50%reduction of serum M protein+reduction in 24-hr urinary M protein by≥90%/ to<200mg/24-hr or ≥50%decrease in difference between involved-uninvolved FLC levels/≥50%reduction in bone marrow plasma cells,if≥30%at baseline/≥50%soft tissue plasmacytoma size reduction. (NCT02917941)
Timeframe: Up to approximately 33 months

Interventionpercentage of participants (Number)
Ixazomib 4 mg + Lenalidomide 25 mg + Dexamethasone 40 mg84.4

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Number of Participants With One or More Treatment-emergent Adverse Events (TEAEs)

An adverse event (AE) is any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it was related to the medicinal product. A TEAE is defined as any AE that occurred after administration of the first dose of any study drug through 30 days after the last dose of any study drug. (NCT02917941)
Timeframe: Up to approximately 33 months

InterventionParticipants (Count of Participants)
Ixazomib 4 mg + Lenalidomide 25 mg + Dexamethasone 40 mg34

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Duration of Response (DOR)

DOR was measured as time in months from date of first documentation of response, VGPR or better, and ORR (CR+PR (including sCR and VGPR) or better, to date of first documented PD among participants who responded to treatment. Response was assessed by investigator using IMWG Criteria. CR:negative immunofixation in serum and urine and; disappearance of any soft tissue plasmacytomas and;<5% plasma cells in bone marrow. sCR:CR plus normal FLC ratio, absence of clonal plasma cells by immunohistochemistry or 2- to 4-color flow cytometry. VGPR:serum and urine M-protein detectable by immunofixation but not on electrophoresis/≥90% reduction in serum M-protein plus urine M-protein level <100 mg/24 hours. PR:≥50% reduction of serum M protein+reduction in 24-hour urinary M protein by ≥90%/ to <200 mg/24-hour or ≥50% decrease in difference between involved and uninvolved FLC levels/≥50% reduction in bone marrow plasma cells, if ≥30% at baseline/≥50% reduction in size of soft tissue plasmacytomas. (NCT02917941)
Timeframe: Up to approximately 33 months

Interventionmonths (Median)
VGPR or betterORR
Ixazomib 4 mg + Lenalidomide 25 mg + Dexamethasone 40 mgNA21.65

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Culturable HIV by Quantitative Viral Outgrowth Assay

Infectious units per million CD4 T cells (NCT02946047)
Timeframe: 24 weeks

,,,
Interventionunits per million (Median)
Baseline24 weeks
Ixazomib 1 mg0.490.30
Ixazomib 2 mg0.300.48
Ixazomib 3 mg0.620.82
Ixazomib 4 mg1.541.31

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Cell Associated HIV DNA in CD4 T Cell Subsets

HIV copies per million CD4 T cells (NCT02946047)
Timeframe: 24 weeks

,,,
Interventioncopies per million (Median)
Baseline24 weeks
Ixazomib 1 mg378394
Ixazomib 2 mg626425
Ixazomib 3 mg664.8624
Ixazomib 4 mg416481

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CD4/CD8 Ratio

CD4/CD8 T cell count ratio (NCT02946047)
Timeframe: 24 weeks

,,,
Interventionratio (Median)
Baseline24 weeks
Ixazomib 1 mg1.451.84
Ixazomib 2 mg1.140.92
Ixazomib 3 mg1.281.17
Ixazomib 4 mg1.581.75

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Absolute CD8 T Cell Count

Cells per microliter (NCT02946047)
Timeframe: 24 weeks

,,,
Interventioncells/mmˆ(3) (Median)
Baseline24 weeks
Ixazomib 1 mg508387
Ixazomib 2 mg803885
Ixazomib 3 mg1014689
Ixazomib 4 mg573416

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Absolute CD4 T Cell Count

Cells per microliter (NCT02946047)
Timeframe: 24 weeks

,,,
Interventioncells/mmˆ(3) (Median)
Baseline24 weeks
Ixazomib 1 mg724714
Ixazomib 2 mg914809
Ixazomib 3 mg1130765
Ixazomib 4 mg735632

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Incidence of Treatment-Emergent Adverse Events

Number of treatment-emergent adverse events experienced by subjects as defined by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (NCT02946047)
Timeframe: 7 months

InterventionParticipants (Count of Participants)
Ixazomib 1 mg0
Ixazomib 2 mg0
Ixazomib 3 mg0
Ixazomib 4 mg0

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Number of Participants Reporting One or More Adverse Events (AEs)

An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. (NCT03169361)
Timeframe: Up to 24 Week (From start of administration to the end of 6 cycles)

InterventionParticipants (Count of Participants)
Ixazomib 4 mg642

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Number of Participants Who Had One or More Adverse Drug Reactions (ADRs)

An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. Adverse drug reaction (ADR) refers to AE related to administered drug. (NCT03169361)
Timeframe: Up to 24 Week (From start of administration to the end of 6 cycles)

InterventionParticipants (Count of Participants)
Ixazomib 4 mg573

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Overall Survival (OS)

OS was defined as the time from randomization to death from any cause, up to 3 years are reported. (NCT03170882)
Timeframe: From date of randomization to death due to any cause (Up to approximately 3 years)

Interventionmonths (Median)
Pomalidomide 4 mg + Dexamethasone 40 mgNA
Ixazomib 4 mg + Dexamethasone 20 mg18.8

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Health Care Utilization (HU): Number of Participants With at Least One Medical Encounter

Healthcare resources used during medical encounters included hospitalizations, emergency room stays, or outpatient visits. A hospitalization was defined as at least 1 overnight stay in an Intensive Care Unit and/or non-Intensive Care Unit (acute care unit, palliative care unit, and hospice). (NCT03170882)
Timeframe: Up to approximately 3 years

,
InterventionParticipants (Count of Participants)
HospitalizationsEmergency Room StaysOutpatient Visits
Ixazomib 4 mg + Dexamethasone 20 mg231132
Pomalidomide 4 mg + Dexamethasone 40 mg16929

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Duration of Response (DOR)

DOR: Time from first documentation of CR/PR/VGPR to first documentation of PD. Per IMWG criteria, PR:>=50% reduction of serum M protein+reduction in 24-hour urinary M protein by >=90% to <200 mg/24-hour or >=50% decrease in difference between involved and uninvolved FLC levels/ >=50% reduction in bone marrow plasma cells, if >=30% at Baseline/ >=50% reduction in size of soft tissue plasmacytomas. VGPR: serum+urine M-protein detectable by immunofixation but not on electrophoresis/ >=90% reduction in serum M-protein + urine M-protein level <100 mg/24-hour. CR:negative immunofixation on serum + urine+disappearance of soft tissue plasmacytomas+<5% plasma cells in bone marrow. PD:serum M-component increase >=0.5 g/dl or urine M-component increase >=200 mg/24-hour/ difference between involved and uninvolved FLC levels increase >10 mg/dl or bone marrow plasma cell >=10%/development of new/ increase in size of existing bone lesions or soft tissue plasmacytoma or development of hypercalcemia. (NCT03170882)
Timeframe: From date of first documentation of CR, VGPR or PR until first occurrence of confirmed disease progression or death due to any cause, whichever occurs first (Up to approximately 3 years)

Interventionmonths (Median)
Pomalidomide 4 mg + Dexamethasone 40 mg14.3
Ixazomib 4 mg + Dexamethasone 20 mg14.8

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Percentage of Participants With Overall Response

Overall Response Rate (ORR) was defined as the percentage of participants who achieved partial response (PR), very good partial response (VGPR), or complete response (CR) based on laboratory results and IRC assessment using modified IMWG criteria. PR: >=50% reduction of serum M protein + reduction in 24-hour urinary M protein by >=90% or to <200 mg/24-hour; if M protein is not measurable, >=50% decrease in difference between involved and uninvolved FLC levels is required; if not measurable by FLC, >=50% reduction in bone marrow plasma cells, when baseline value >=30% and; if present at baseline, >=50% reduction in size of soft tissue plasmacytomas is required. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein + urine M-protein level <100 mg/24-hour. CR: negative immunofixation on serum + urine; disappearance of soft tissue plasmacytomas; <5 % plasma cells in bone marrow. (NCT03170882)
Timeframe: From date of randomization until first documentation of CR, VGPR or PR (Up to approximately 3 years)

Interventionpercentage of participants (Number)
Pomalidomide 4 mg + Dexamethasone 40 mg41
Ixazomib 4 mg + Dexamethasone 20 mg38

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Time to Progression (TTP)

TTP was defined as the time from the date of randomization to first documentation of PD. Per IMWG criteria, PD required 1 of the following: Increase of >=25% from nadir in: Serum M-component (increase must be >=0.5 g/dl; Urine M-component (increase must be >=200 mg/24-hour); In participants without measurable serum and urine M-protein levels difference between involved and uninvolved FLC levels increase of >10 mg/dl; In participants without measurable serum and urine M protein levels and without measurable disease by FLC level: Bone marrow plasma cell percentage must be >=10%; Development of new or increase in size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (>11.5 mg/dL corrected serum calcium) attributed solely to plasma cell proliferative disease. (NCT03170882)
Timeframe: From date of randomization until first occurrence of confirmed disease progression or death due to any cause, whichever occurs first (Up to approximately 3 years)

Interventionmonths (Median)
Pomalidomide 4 mg + Dexamethasone 40 mg5.1
Ixazomib 4 mg + Dexamethasone 20 mg8.4

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HU: Duration of Medical Encounters

Duration of healthcare resources used during medical encounters including hospitalizations, emergency room stays, or outpatient visits was reported in days. A hospitalization was defined as at least 1 overnight stay in an Intensive Care Unit and/or non-Intensive Care Unit (acute care unit, palliative care unit, and hospice). (NCT03170882)
Timeframe: Up to approximately 3 years

,
Interventiondays (Median)
HospitalizationsEmergency Room StaysOutpatient Visits
Ixazomib 4 mg + Dexamethasone 20 mg1.01.03.0
Pomalidomide 4 mg + Dexamethasone 40 mg2.01.04.0

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HRQOL Based on EORTC Multiple Myeloma Module 20 (EORTC QLQ-MY20) Score

The EORTC QLQ-MY20 has 20 items across 4 independent subscales, 2 symptoms scales (disease symptoms, side effects of treatment), and 2 functional subscales (body image, future perspective). Scores were averaged and transformed to 0-100 scale. Higher scores for the future perspective scale indicate better perspective of the future, for the body image scale indicate better body image and for the disease symptoms scale indicate higher level of symptomatology. (NCT03170882)
Timeframe: Baseline and End of Treatment (Up to 28 cycles, each cycle was of 28 days)

,
Interventionscore on a scale (Mean)
Disease Symptoms: BaselineDisease Symptoms: End of TreatmentSide Effects of Treatment: BaselineSide Effects of Treatment: End of TreatmentBody Image: BaselineBody Image: End of TreatmentFuture Perspective: BaselineFuture Perspective: End of Treatment
Ixazomib 4 mg + Dexamethasone 20 mg72.468.981.477.882.983.767.564.0
Pomalidomide 4 mg + Dexamethasone 40 mg73.273.581.074.481.575.058.857.9

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Health-Related Quality of Life (HRQOL) Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire- Core 30 (EORTC QLQ-C30) Physical Domain Score

The EORTC QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status/quality of life (QOL) scale. The physical domain consisted of 5 items covering participant's daily physical activities on a scale from 1 (not at all) to 4 (very much). Raw scores were linearly transformed to a total score between 0-100, with a high score indicating better physical functioning. (NCT03170882)
Timeframe: Baseline and End of Treatment (Up to 28 cycles, each cycle was of 28 days)

,
Interventionscore on a scale (Mean)
BaselineEnd of Treatment
Ixazomib 4 mg + Dexamethasone 20 mg67.956.5
Pomalidomide 4 mg + Dexamethasone 40 mg67.052.4

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HRQOL Based on EORTC QLQ-C30 SubScale Score

The EORTC QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a QOL scale. Most of the 30 items had 4 response levels (not at all, a little, quite a bit, and very much), with 2 questions relying on a 7-point numeric rating scale. Each subscale raw score were linearly transformed to a total score between 0 to 100. For the functional scales and the global health status/QOL scale, higher scores represent better QOL; for the symptom scales, lower scores represent better QOL. The Physical domain of the functional subscale is reported in the secondary outcome measure 7. (NCT03170882)
Timeframe: Baseline and End of Treatment (Up to 28 cycles, each cycle was of 28 days)

,
Interventionscore on a scale (Mean)
Global Health Status/QoL: BaselineGlobal Health Status/QoL: End of TreatmentRole (Functional Scale): BaselineRole (Functional Scale): End of TreatmentEmotional (Functional Scale): BaselineEmotional (Functional Scale): End of TreatmentCognitive(Functional Scale): BaselineCognitive (Functional Scale): End of TreatmentSocial (Functional Scale): BaselineSocial (Functional Scale): End of TreatmentFatigue (Symptom Scale): BaselineFatigue (Symptom Scale): End of TreatmentNausea/Vomiting (Symptom Scale): BaselineNausea/Vomiting (Symptom Scale): End of TreatmentPain (Symptom Scale): BaselinePain (Symptom Scale): End of TreatmentDyspnea (Symptom Scale): BaselineDyspnea (Symptom Scale): End of TreatmentInsomnia (Symptom Scale): BaselineInsomnia (Symptom Scale): End of TreatmentAppetite Loss (Symptom Scale): BaselineAppetite Loss (Symptom Scale): End of TreatmentConstipation (Symptom Scale): BaselineConstipation (Symptom Scale): End of TreatmentDiarrhea (Symptom Scale): BaselineDiarrhea (Symptom Scale): End of TreatmentFinancial Difficulties (Symptom Scale): BaselineFinancial Difficulties (Symptom Scale): End of Treatment
Ixazomib 4 mg + Dexamethasone 20 mg60.848.267.949.283.172.884.077.475.769.861.050.394.892.965.253.219.024.629.529.414.323.011.419.816.716.317.112.7
Pomalidomide 4 mg + Dexamethasone 40 mg57.047.867.447.674.967.679.669.672.263.160.050.896.788.761.151.225.240.532.636.922.234.513.325.017.819.022.216.7

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Progression Free Survival (PFS)

PFS: Time from randomization to first occurrence of confirmed progressive disease (PD) as assessed by investigator by International Myeloma Working Group(IMWG) response criteria/death from any cause, whichever occurs first. PD requires following: Increase of >=25 % from nadir in: Serum M component (increase must be >=0.5 gram per deciliter [g/dl]); Urine M-component (increase must be >=200 milligram [mg]/24-hour); In participants without measurable serum and urine M-protein levels difference between involved and uninvolved free light chain (FLC) increase of >10 mg/dl; In participants without measurable serum and urine M protein levels and without measurable disease by FLC level: bone marrow plasma cell percentage must be >=10%; Development of new/increase in size of existing bone lesions/soft tissue plasmacytomas; development of hypercalcemia (>11.5mg/dL corrected serum calcium) attributed solely to plasma cell proliferative disease. (NCT03170882)
Timeframe: From date of randomization until first occurrence of confirmed disease progression or death due to any cause, whichever occurs first (Up to approximately 3 years)

Interventionmonths (Median)
Pomalidomide 4 mg + Dexamethasone 40 mg4.8
Ixazomib 4 mg + Dexamethasone 20 mg7.1

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Time to Response

Time to response was defined as the time from randomization to the first documentation of PR/VGPR/CR. Per IMWG criteria, PR: >=50% reduction of serum M protein + reduction in 24-hour urinary M protein by >=90% or to <200 mg/24-hour; if M-protein is not measurable, >=50% decrease in difference between involved and uninvolved FLC levels is required; if not measurable by FLC, >=50% reduction in bone marrow plasma cells, when Baseline value >=30% and; if present at Baseline, >=50% reduction in size of soft tissue plasmacytomas is required. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein + urine M-protein level <100 mg/24-hour. CR: negative immunofixation on serum + urine; disappearance of soft tissue plasmacytomas; <5% plasma cells in bone marrow. (NCT03170882)
Timeframe: From date of randomization until first documentation of CR, VGPR or PR (Up to approximately 3 years)

Interventionmonths (Median)
Pomalidomide 4 mg + Dexamethasone 40 mg1.1
Ixazomib 4 mg + Dexamethasone 20 mg2.0

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HRQOL Based on EuroQol Visual Analogue Scale (EQ VAS) Score

The EQ VAS records the respondent's self-rated health on a 20 centimeter (cm), vertical, visual analogue scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). The scores from all dimensions were combined into a single index score that was reported, where higher score was better quality of life. (NCT03170882)
Timeframe: Baseline and End of Treatment (Up to 28 cycles, each cycle was of 28 days)

,
Interventionscore on a scale (Mean)
BaselineEnd of Treatment
Ixazomib 4 mg + Dexamethasone 20 mg64.455.9
Pomalidomide 4 mg + Dexamethasone 40 mg59.246.9

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Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score

EQ-5D-5L comprises of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each rated on 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, 5= extremely severe problems. Higher scores indicated greater levels of problems across the five dimensions. (NCT03170882)
Timeframe: End of Treatment (Up to 28 cycles, each cycle was of 28 days)

,
InterventionParticipants (Count of Participants)
Mobility: 1 = I Have no Problems in Walking AboutMobility: 2 = I Have Slight Problems in Walking AboutMobility: 3 = I Have Moderate Problems in Walking AboutMobility: 4 = I Have Severe Problems in Walking AboutMobility: 5 = I am Unable to Walk AboutSelf-Care: 1 = I Have no Problems Washing or Dressing MyselfSelf-Care: 2 = I Have Slight Problems Washing or Dressing MyselfSelf-Care: 3 = I Have Moderate Problems Washing or Dressing MyselfSelf-Care: 4 = I Have Severe Problems Washing or Dressing MyselfSelf-Care: 5 = I am Unable to Wash or Dress MyselfUsual Activities: 1 = I Have no Problems Doing my Usual ActivitiesUsual Activities: 2 = I Have Slight Problems Doing my Usual ActivitiesUsual Activities: 3 = I Have Moderate Problems Doing my Usual ActivitiesUsual Activities: 4 = I Have Severe Problems Doing my Usual ActivitiesUsual Activities: 5 = I am Unable to do my Usual ActivitiesPain/Discomfort: 1 = I Have no Pain or DiscomfortPain/Discomfort: 2 = I Have Slight Pain or DiscomfortPain/Discomfort: 3 = I Have Moderate Pain or DiscomfortPain/Discomfort: 4 = I Have Severe Pain or DiscomfortPain/Discomfort: 5 = I Have Extreme Pain or DiscomfortAnxiety/Depression: 1 = I Have no Pain or DiscomfortAnxiety/Depression: 2 = I Have no Pain or DiscomfortAnxiety/Depression: 3 = I Have no Pain or DiscomfortAnxiety/Depression: 4 = I Have no Pain or DiscomfortAnxiety/Depression: 5 = I Have no Pain or Discomfort
Ixazomib 4 mg + Dexamethasone 20 mg91211812110442109127381015621913612
Pomalidomide 4 mg + Dexamethasone 40 mg5688013653047871351360681120

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Number of Patients Experiencing Adverse Events Graded According to the Medical Dictionary for Regulatory Activities (MedDRA) Version (v) 12.1

The number of patients experiencing a grade 3 or greater adverse event will be reported. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. (NCT03202628)
Timeframe: 36 months

InterventionParticipants (Count of Participants)
Treatment (Ixazomib, Pomalidomide, Dexamethasone, ASCT)7

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Percent of Patients Alive at 30 Months

The distribution of overall survival will be estimated using the method of Kaplan-Meier. (NCT03202628)
Timeframe: 30 months

Interventionpercentage of patients (Number)
Treatment (Ixazomib, Pomalidomide, Dexamethasone, ASCT)75

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Percentage of Participants With Greater Than or Equal to (>=) Very Good Partial Response (VGPR) Rate

Will be estimated by the number of patients who achieve a stringent complete response (sCR), complete response CR, or VGPR divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true overall >= VGPR will be calculated. (NCT03202628)
Timeframe: 30 months

Interventionpercentage of patients (Number)
Treatment (Ixazomib, Pomalidomide, Dexamethasone, ASCT)25

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Overall Response Rate

Will be estimated by the number of patients who achieve a stringent complete response (sCR), complete response CR, very good partial response (VGPR), or partial response (PR) divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true overall response rate will be calculated. (NCT03202628)
Timeframe: 30 months

Interventionpercentage of patients (Number)
Treatment (Ixazomib, Pomalidomide, Dexamethasone, ASCT)50

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Progression-free Survival at 18 Months (PFS18) Defined as the Proportion of Patients Alive and Free From Disease Progression at 18 Months From Study Entry

The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportion will be calculated. If patients are censored prior to 18 months post registration, a Kaplan Meier (Kaplan, E. and Meier, P., 1958) estimate for PFS18 along with the 95% confidence intervals will be reported. (NCT03202628)
Timeframe: 18 months

Interventionproportion of participants (Number)
Treatment (Ixazomib, Pomalidomide, Dexamethasone, ASCT)0.3750

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Change in Circulating APRIL Levels as Assessed by APRIL ELISA Assay

B cell activating factor belonging to a proliferation-inducing ligand (APRIL) are members of the TNF ligand superfamily. Plasma APRIL ELISA assay can be performed in 2-3 hours. It can be used as a marker of disease activity in sensitized patients. (NCT03213158)
Timeframe: Baseline, 3 months

Interventionpg/ml (Median)
Baseline3 months
Highly Sensitized Kidney Transplant Candidates163172

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Safety of Ixazomib as Assesses by Percentage of Participants With Malignancies Within 12 Months

(NCT03213158)
Timeframe: up to 12 months

InterventionParticipants (Count of Participants)
Highly Sensitized Kidney Transplant Candidates0

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Safety of Ixazomib: as Assesses by Percentage of Participants With Distal Neuropathy Within 12 Months

(NCT03213158)
Timeframe: up to 12 months

InterventionParticipants (Count of Participants)
Highly Sensitized Kidney Transplant Candidates1

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Change in Circulating BAFF Levels as Assessed by BAFF ELISA Assay

B cell activating factor belonging to the TNF family (BAFF) are members of the TNF ligand superfamily. Plasma BAFF ELISA assays can be performed in 2-3 hours. It can be used as a marker of disease activity in sensitized patients. (NCT03213158)
Timeframe: Baseline, 3 months

Interventionpg/ml (Mean)
Baseline3 months
Highly Sensitized Kidney Transplant Candidates126160

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Safety of Ixazomib as Assesses by Percentage of Participants With Thrombocytopenia Within 12 Months

(NCT03213158)
Timeframe: up to 12 months

InterventionParticipants (Count of Participants)
Highly Sensitized Kidney Transplant Candidates0

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Safety of Ixazomib as Assesses by Percentage of Participants With Hematological Complications Within 12 Months

Hematological complications include leucopenia, anemia, and thrombocytopenia (NCT03213158)
Timeframe: up to 12 months

InterventionParticipants (Count of Participants)
Highly Sensitized Kidney Transplant Candidates2

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Safety of Ixazomib as Assesses by Percentage of Participants With Gastrointestinal Symptoms Within 12 Months

(NCT03213158)
Timeframe: up to 12 months

InterventionParticipants (Count of Participants)
Highly Sensitized Kidney Transplant Candidates5

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Safety of Ixazomib as Assesses by Percentage of Participants With Cardiovascular Complications Within 12 Months

(NCT03213158)
Timeframe: up to 12 months

InterventionParticipants (Count of Participants)
Highly Sensitized Kidney Transplant Candidates2

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Safety of Ixazomib as Assesses by Percentage of Participants Caught Infection Within 12 Months

(NCT03213158)
Timeframe: up to 12 months

InterventionParticipants (Count of Participants)
Highly Sensitized Kidney Transplant Candidates5

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Efficacy of Ixazomib: Percentage of Participants With > 20 Percent Decline in Calculated Panel Reactive Antibody (cPRA)

(NCT03213158)
Timeframe: up to 12 months

InterventionParticipants (Count of Participants)
Highly Sensitized Kidney Transplant Candidates0

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Efficacy of Ixazomib: Percentage of Participants Received Successful Kidney Transplantation Within 12 Months

(NCT03213158)
Timeframe: up to 12 months

InterventionParticipants (Count of Participants)
Highly Sensitized Kidney Transplant Candidates2

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Number of Participants With Minimal Residual Disease (MRD) Positive or Negative in Bone Marrow in Participants Who Achieved CR

MRD was measured by the flow cytometry method using bone marrow aspiration. Reported data were numbers of participants with MRD positive and negative in bone marrow in participants who achieved CR. MRD positive was categorized into three sensitivity levels with the numbers of cells counted (10^-4 to - Max; 10^-5 to 10^-4; 10^-6 to 10^-5). MRD negativity is defined as absence of MRD and MRD positivity is defined as presence of MRD. If a participant is MRD-positive at their first evaluation and MRD-negative after re-examination, the participant will be considered to be MRD-negative. CR will be assessed by IMWG Criteria. (NCT03416374)
Timeframe: Up to 39 months as a maximum

,,
InterventionParticipants (Count of Participants)
Sensitivity Level; 10^-4=< - MaxSensitivity Level; 10^-5=< - <10^-4Sensitivity Level; 10^-6=< - <10^-5Negative
[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy1215
[Overall]; Combination Therapy + Ixazomib Therapy1325
[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy0110

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Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score

EORTC QLQ-MY20 has 20 items across 4 independent subscales, 2 functional subscales (body image, future perspective), and 2 symptoms scales (disease symptoms, and side effects of treatment). Scores are averaged, and transformed to 0-100 scale. For the functional scales, high scores represent improvement. For the symptom scales, higher scores represent worsening. (NCT03416374)
Timeframe: Baseline and End of Treatment (Up to 23 cycles for VRd Group, Up to 32 cycles for KRd and Overall Group, each cycle was of 28 days)

,
InterventionScore on a Scale (Mean)
Disease Symptoms: BaselineDisease Symptoms: Cycle 23Disease Symptoms: Cycle 32Side-Effects of Treatment: BaselineSide-Effects of Treatment: Cycle 23Side-Effects of Treatment: Cycle 32Body Image: BaselineBody Image: Cycle 23Body Image: Cycle 32Future Perspective: BaselineFuture Perspective: Cycle 23Future Perspective: Cycle 32
[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy19.234.632.7816.6016.0518.5223.0816.6716.6744.1635.1927.78
[Overall]; Combination Therapy + Ixazomib Therapy19.883.972.7816.6114.2918.5225.9314.2916.6747.1631.7527.78

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Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score

EORTC QLQ-MY20 has 20 items across 4 independent subscales, 2 functional subscales (body image, future perspective), and 2 symptoms scales (disease symptoms, and side effects of treatment). Scores are averaged, and transformed to 0-100 scale. For the functional scales, high scores represent improvement. For the symptom scales, higher scores represent worsening. (NCT03416374)
Timeframe: Baseline and End of Treatment (Up to 23 cycles for VRd Group, Up to 32 cycles for KRd and Overall Group, each cycle was of 28 days)

InterventionScore on a Scale (Mean)
Disease Symptoms: BaselineDisease Symptoms: Cycle 23Side-Effects of Treatment: BaselineSide-Effects of Treatment: Cycle 23Body Image: BaselineBody Image: Cycle 23Future Perspective: BaselineFuture Perspective: Cycle 23
[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy24.07016.673.7044.44066.6711.11

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Percentage of Participants Who Achieve or Maintain Any Best Response

Best response is defined as the cumulative numbers of participants who achieve each level of best response including PR, VGPR and CR assessed with IMWG Criteria, after each cycle of treatment. Per IMWG criteria, PR (partial response): ≥50% reduction of serum M protein+reduction in 24-hour urinary M protein by ≥90%/ to <200 mg/24-hour or ≥50% decrease in difference between involved and uninvolved free light chain (FLC) levels/ ≥50% reduction in bone marrow plasma cells, if ≥30% at baseline/ ≥50% reduction in size of soft tissue plasmacytomas. VGPR (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine Mprotein level <100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+<5% plasma cells in bone marrow. (NCT03416374)
Timeframe: Up to 39 months as a maximum

,,
InterventionPercentage of Participants (Number)
CRVGPRPR
[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy23.120.528.2
[Overall]; Combination Therapy + Ixazomib Therapy24.417.831.1
[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy33.3050.0

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Relative Dose Intensity (RDI)

RDI for each study drug is defined as 100*(Total amount of dose taken)/(Total prescribed dose of treated cycles), where total prescribed dose equals [dose prescribed at enrollment* number of prescribed doses per cycle* the number of treated cycles]. (NCT03416374)
Timeframe: Up to 39 months as a maximum

InterventionPercent (Median)
Bortezomib, IxazomibCarfilzomib, IxazomibBortezomib/Carfilzomib, IxazomibLenalidomideDexamethasone
[Overall]; Combination Therapy + Ixazomib Therapy71.9387.7083.2447.1848.61

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Overall Survival (OS) From the Start of Study Treatment

OS was defined as the period from the first dose of treatment in Treatment Period I to the time when death (regardless of the cause of death) was confirmed. Participants who were still alive were censored at the last confirmed date of survival or the date of data cut-off, whichever was earlier. (NCT03416374)
Timeframe: Up to 39 months as a maximum

InterventionMonths (Median)
[VRd]; Bortezomib + Lenalidomide + Dexamethasone TherapyNA
[KRd]; Carfilzomib + Lenalidomide + Dexamethasone TherapyNA
[Overall]; Combination Therapy + Ixazomib TherapyNA

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Healthcare Resource Utilization (HCRU): Duration of Hospital Stay Per Participants

HCRU was calculated from Exposure-adjusted rate of hospitalization events (per participants-months) and the duration of hospitalization among participants in Treatment Period I and Treatment Period II. Duration of hospital stay per participants in Treatment Period I and Treatment Period II was reported. (NCT03416374)
Timeframe: Up to 39 months as a maximum

InterventionDays (Mean)
[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy14.8
[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy19.4
[Overall]; Combination Therapy + Ixazomib Therapy18.8

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Duration of Response (DOR)

DOR is defined as the time from the date of first documentation of response ≥PR to the date of first documentation of PD or death due to any cause. PR and PD will be assessed with IMWG Criteria. Per IMWG criteria, PR (partial response): ≥50% reduction of serum M protein+reduction in 24-hour urinary M protein by ≥90%/ to <200 mg/24-hour or ≥50% decrease in difference between involved and uninvolved free light chain (FLC) levels/ ≥50% reduction in bone marrow plasma cells, if ≥30% at baseline/ ≥50% reduction in size of soft tissue plasmacytomas. VGPR (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine Mprotein level <100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+<5% plasma cells in bone marrow. (NCT03416374)
Timeframe: Up to 39 months as a maximum

InterventionMonths (Median)
[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy15.31
[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy28.03
[Overall]; Combination Therapy + Ixazomib Therapy28.03

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Duration of Therapy (DOT)

DOT is defined as the treatment duration of study drug at study treatment Period I. (NCT03416374)
Timeframe: Up to 39 months as a maximum

InterventionMonths (Median)
[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy14.69
[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy12.43
[Overall]; Combination Therapy + Ixazomib Therapy12.43

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Evaluation of Modified Quality-Adjusted Life-Years (QALYs)

Modified QALYs was calculated from the score of EORTC QLQ-C30. The health-related quality of life scale score of EORTC QLQ-C30 was converted into a utility value ranging from 0 (dead) to 1 (perfect health), and used to adjust the value of survival years; this value was assessed as the modified QALY. (NCT03416374)
Timeframe: Up to 39 months as a maximum

InterventionQuality-Adjusted Life-Years (Median)
[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy0.467
[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy0.534
[Overall]; Combination Therapy + Ixazomib Therapy0.518

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Healthcare Resource Utilization (HCRU): Number of Events With Hospitalization Per Participants-Month

HCRU was calculated from Exposure-adjusted rate of hospitalization events (per participants-months) and the duration of hospitalization among participants in Treatment Period I and Treatment Period II. Number of events with hospitalization per participants-month in Treatment Period I and Treatment Period II was reported. (NCT03416374)
Timeframe: Up to 39 months as a maximum

InterventionNumber of Events per Participants-Month (Number)
[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy1.9
[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy2.9
[Overall]; Combination Therapy + Ixazomib Therapy2.7

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Percentage of Participants Continuing Treatment With Ixazomib at 12 Months From the Start of Study Treatment

(NCT03416374)
Timeframe: 12 months

InterventionPercentage of Participants (Number)
[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy50.0
[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy35.9
[Overall]; Combination Therapy + Ixazomib Therapy37.8

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Percentage of Participants Who Achieved VGPR or Better (CR + VGPR)

VGPR or better (CR + VGPR) were assessed by IMWG Criteria. Per IMWG criteria, PR (partial response): ≥50% reduction of serum M protein+reduction in 24-hour urinary M protein by ≥90%/ to <200 mg/24-hour or ≥50% decrease in difference between involved and uninvolved free light chain (FLC) levels/ ≥50% reduction in bone marrow plasma cells, if ≥30% at baseline/ ≥50% reduction in size of soft tissue plasmacytomas. VGPR (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine Mprotein level <100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+<5% plasma cells in bone marrow. (NCT03416374)
Timeframe: Up to 39 months as a maximum

InterventionPercentage of Participants (Number)
[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy33.3
[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy43.6
[Overall]; Combination Therapy + Ixazomib Therapy42.2

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Percentage of Participants With Bone Lesions (Bone Evaluation)

(NCT03416374)
Timeframe: Up to 39 months as a maximum

InterventionPercentage of Participants (Number)
[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy100.0
[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy59.1
[Overall]; Combination Therapy + Ixazomib Therapy64.0

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PFS From the Start of Study Treatment

PFS was defined as the period from the first dose of treatment in Treatment Period I to the time of confirmed PD or confirmed death (regardless of the cause of death), whichever is earlier. PFS was assessed by IMWG Criteria. (NCT03416374)
Timeframe: Up to 39 months as a maximum

InterventionMonths (Median)
[VRd]; Bortezomib + Lenalidomide + Dexamethasone TherapyNA
[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy28.96
[Overall]; Combination Therapy + Ixazomib Therapy28.96

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Progression-Free Survival (PFS) Rate at 12 Months From the Start of Study Treatment

PFS rate was defined as the percentage of participants who were alive and have not had disease progression at 12 months after the date of first dose of treatment in Treatment Period I. PFS was assessed by International Myeloma Working Group (IMWG) Criteria (2014 version). Per IMWG criteria, progressive disease (PD): serum M-component increase ≥0.5 g/dl or urine M-component increase ≥200 mg/24-hour/ difference between involved and uninvolved free light chain (FLC) levels increase >10 mg/dl or bone marrow plasma cell ≥10%/ development of new/ increase in size of existing bone lesions or soft tissue plasmacytoma or development of hypercalcemia. (NCT03416374)
Timeframe: Up to 12 months

InterventionPercentage of Participants (Number)
[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy50.0
[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy48.7
[Overall]; Combination Therapy + Ixazomib Therapy48.9

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Number of Participants Reporting One or More Treatment-Emergent AEs (TEAEs)

An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. (NCT03416374)
Timeframe: Up to 39 months as a maximum

InterventionParticipants (Count of Participants)
[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy6
[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy35
[Overall]; Combination Therapy + Ixazomib Therapy41

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Overall Response Rate (ORR)

ORR is defined as the percentage of participants who achieve a best response of PR or better including stringent complete response (sCR), VGPR and PR assessed with IMWG Criteria, after the start of the study treatment. Per IMWG criteria, PR (partial response): ≥50% reduction of serum M protein+reduction in 24-hour urinary M protein by ≥90%/ to <200 mg/24-hour or ≥50% decrease in difference between involved and uninvolved free light chain (FLC) levels/ ≥50% reduction in bone marrow plasma cells, if ≥30% at baseline/ ≥50% reduction in size of soft tissue plasmacytomas. VGPR (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine Mprotein level <100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+<5% plasma cells in bone marrow. (NCT03416374)
Timeframe: Up to 39 months as a maximum

InterventionPercentage of Participants (Number)
[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy83.3
[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy71.8
[Overall]; Combination Therapy + Ixazomib Therapy73.3

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Percentage of Participants Who Achieve or Maintain Any Best Response

Best response is defined as the cumulative numbers of participants who achieve each level of best response including partial response (PR), very good PR (VGPR) and complete response (CR) assessed with IMWG Criteria after each cycle of treatment. Per IMWG criteria, PR: ≥50% reduction of serum M protein+reduction in 24-hour urinary M protein by ≥90%/ to <200 mg/24-hour or ≥50% decrease in difference between involved and uninvolved free light chain (FLC) levels/ ≥50% reduction in bone marrow plasma cells, if ≥30% at baseline/ ≥50% reduction in size of soft tissue plasmacytomas. VGPR: serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine M-protein level <100 mg/24-hour. CR: negative immunofixation on serum+urine +disappearance of soft tissue plasmacytomas+<5% plasma cells in bone marrow. (NCT03433001)
Timeframe: Up to 36 months as a maximum

InterventionPercentage of Participants (Number)
CRVGPRPR
Ixazomib + Lenalidomide + Dexamethasone20.08.522.0

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Relative Dose Intensity (RDI)

RDI is defined as 100*(Total amount of dose taken)/(Total prescribed dose of treated cycles), where total prescribed dose equals [dose prescribed at enrollment* number of prescribed doses per cycle* the number of treated cycles]. (NCT03433001)
Timeframe: Up to 36 months as a maximum

InterventionPercent (Mean)
IxazomibLenalidomideDexamethasone
Ixazomib + Lenalidomide + Dexamethasone66.4944.7241.07

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Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score

EORTC QLQ-MY20 has 20 items across 4 independent subscales, 2 functional subscales (body image, future perspective), and 2 symptoms scales (disease symptoms, and side effects of treatment). Scores are averaged, and transformed to 0-100 scale. For the future perspective scale, higher score = better perspective of the future. For the body image scale, higher scores = better body image. Higher score for the disease symptoms scale = higher level of symptomatology. (NCT03433001)
Timeframe: Baseline and End of Treatment (Up to 37 cycles, each cycle was of 28 days)

InterventionScore on a Scale (Mean)
Disease Symptoms: BaselineDisease Symptoms: End of TreatmentSide-Effects of Treatment: BaselineSide-Effects of Treatment: End of TreatmentBody Image: BaselineBody Image: End of TreatmentFuture Perspective: BaselineFuture Perspective: End of Treatment
Ixazomib + Lenalidomide + Dexamethasone19.3311.1117.8016.6728.1816.6742.4933.33

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Percentage of Participants Who Achieve VGPR or Better (CR+VGPR)

The percentage of participants of CR + VGPR is defined as the rate of participants who achieve a best response of VGPR or better (sCR, CR, or VGPR) according to the IMWG Criteria after the start of the IRd therapy. (NCT03433001)
Timeframe: Up to 36 months as a maximum

InterventionPercentage of Participants (Number)
Ixazomib + Lenalidomide + Dexamethasone31.5

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Percentage of Participants With Bone Lesions (Bone Evaluation)

(NCT03433001)
Timeframe: Up to 36 months as a maximum

InterventionPercentage of Participants (Number)
Ixazomib + Lenalidomide + Dexamethasone21.5

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Progression-Free Survival (PFS)

PFS was defined as the period from the start of ixazomib, lenalidomide, dexamethasone (IRd) therapy in standard medical care to the time of confirmed progressive disease (PD) or confirmed death (regardless of the cause of death), whichever was earlier. PFS was assessed by International Myeloma Working Group (IMWG) Criteria (2014 version). Per IMWG criteria, PD: serum M-component increase ≥ 0.5 g/dl or urine M-component increase ≥ 200 mg/24-hour/ difference between involved and uninvolved free light chain (FLC) levels increase >10 mg/dl or bone marrow plasma cell ≥ 10%/ development of new/ increase in size of existing bone lesions or soft tissue plasmacytoma or development of hypercalcemia. (NCT03433001)
Timeframe: Up to 36 Months as a maximum

InterventionMonths (Median)
Ixazomib + Lenalidomide + Dexamethasone4.79

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Rate of Minimal Residual Disease (MRD) Negativity in Bone Marrow in Participants Who Achieved CR

Rate of MRD will be calculated by the percentage of participants who are MRD-negative. (NCT03433001)
Timeframe: Up to 36 months as a maximum

InterventionPercentage of Participants (Number)
10^-4=< - Max10^-5=< - <10^-410^-6=< - <10^-5Negative
Ixazomib + Lenalidomide + Dexamethasone26.716.76.750.0

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PFS Rate at 12 Months and 24 Months After the Start of Treatment

PFS rate was defined as the percentage of participants who were alive and have not had disease progression at 12 months and 24 months after the date of start of study treatment. PFS was assessed by IMWG Criteria (2014 version). Per IMWG criteria, PD: serum M-component increase ≥ 0.5 g/dl or urine M-component increase ≥ 200 mg/24-hour/ difference between involved and uninvolved FLC levels increase >10 mg/dl or bone marrow plasma cell ≥ 10%/ development of new/ increase in size of existing bone lesions or soft tissue plasmacytoma or development of hypercalcemia. (NCT03433001)
Timeframe: 12 months and 24 months

InterventionPercentage of Participants (Number)
Month 12Month 24
Ixazomib + Lenalidomide + Dexamethasone5741

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Percentage of Participants Who Continue to Receive Treatment at 12 Months and 24 Months After Start of Treatment

(NCT03433001)
Timeframe: 12 months and 24 months

InterventionPercentage of Participants (Number)
Month 12Month 24
Ixazomib + Lenalidomide + Dexamethasone40.021.7

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Overall Survival (OS)

OS is defined as the period from the start of IRd therapy in standard medical care to the time when death (regardless of the cause of death) is confirmed. (NCT03433001)
Timeframe: Up to 36 months as a maximum

InterventionMonths (Median)
Ixazomib + Lenalidomide + Dexamethasone20.23

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Overall Response Rate (ORR)

ORR is defined as the percentage of participants who achieve a best response of PR or better including stringent complete response (sCR), VGPR and PR assessed with IMWG Criteria, after the start of the study treatment. (NCT03433001)
Timeframe: Up to 36 months as a maximum

InterventionPercentage of Participants (Number)
Ixazomib + Lenalidomide + Dexamethasone53.9

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Number of Participants Reporting One or More Treatment-Emergent AEs (TEAEs)

An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. (NCT03433001)
Timeframe: Up to 36 months as a maximum

InterventionParticipants (Count of Participants)
Ixazomib + Lenalidomide + Dexamethasone249

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Duration of Therapy (DOT)

DOT is defined as the treatment duration of IRd therapy. (NCT03433001)
Timeframe: Up to 36 months as a maximum

InterventionDays (Mean)
Ixazomib + Lenalidomide + Dexamethasone353.3

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Time to Progression (TTP)

TTP is defined as the time from the first dose of any study drug treatment to the date of the first documented PD. PD is defined as increase of 25% of lowest response value in one or more of following criteria: serum M-component (absolute increase ≥0.5 g/dl); or urine M-component (absolute increase ≥200 mg/24-hour); difference between involved and uninvolved FLC levels (absolute increase >10 mg/dl); or bone marrow plasma cell percentage (absolute plasma cell percentage ≥10%); development of new/ increase in size of existing bone lesions or soft tissue plasmacytoma; or development of hypercalcemia that can be attributed solely to plasma cell proliferative disorder. (NCT03439293)
Timeframe: Up to data cut-off: 1 January 2022 (Approximately 4 years)

Interventionmonths (Median)
Ixazomib 4 mg + Daratumumab 16 mg/kg + Dexamethasone 20 mg21.1

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Progression-free Survival (PFS)

PFS is defined as time from date of first dose of drug to date of first documentation of progressive disease (PD) or death from any cause, whichever occurs first. Participant without documentation of PD or death were censored at the date of last response assessment that is stable disease (SD) or better. PD is defined as increase of 25% of lowest response value in one or more of following criteria: serum M-component (absolute increase ≥0.5 g/dl); or urine M-component (absolute increase ≥200 mg/24-hour); difference between involved and uninvolved FLC levels (absolute increase >10 mg/dl); or bone marrow plasma cell percentage (absolute plasma cell percentage ≥10%); development of new/ increase in size of existing bone lesions or soft tissue plasmacytoma; or development of hypercalcemia that can be attributed solely to plasma cell proliferative disorder. SD is defined as not meeting criteria for other responses. (NCT03439293)
Timeframe: Up to data cut-off: 1 January 2022 (Approximately 4 years)

Interventionmonths (Median)
Ixazomib 4 mg + Daratumumab 16 mg/kg + Dexamethasone 20 mg16.8

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Percentage of Participants With Very Good Partial Response (VGPR) or Better (Complete Response + VGPR)

Response was assessed using International Myeloma Working Group (IMWG) Criteria. VGPR is defined as serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level< 100 milligram (mg) per 24 hours. The percentage of participants were rounded off to the single decimal point. (NCT03439293)
Timeframe: Up to data cut-off: 1 January 2022 (Approximately 4 years)

Interventionpercentage of participants (Number)
Ixazomib 4 mg + Daratumumab 16 mg/kg + Dexamethasone 20 mg32.2

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Overall Survival (OS)

OS is defined as the time from the date of first dose of any study drug treatment to the date of death. Participant without documentation of death at the time of analysis will be censored at the last visit at which s/he was known to be alive. (NCT03439293)
Timeframe: Up to data cut-off: 1 January 2022 (Approximately 4 years)

Interventionmonths (Median)
Ixazomib 4 mg + Daratumumab 16 mg/kg + Dexamethasone 20 mgNA

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Overall Response Rate (ORR)

ORR is defined as percentage of participants with complete response (CR), VGPR and partial response (PR). CR: Negative immunofixation of serum and urine, disappearance of any soft tissue plasmacytomas, and <5% plasma cells in bone marrow; normal free light chain (FLC) ratio of 0.26-1.65; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein + urine M-protein level <100 mg/24 hours; and PR: >=50% reduction of serum M protein and reduction in 24-hour urinary M protein by >=90%/to <200 mg/24 hours; In addition, if present at baseline, >=50% reduction in size of soft tissue plasmacytomas; no known evidence of progressive/new bone lesions. The percentage of participants were rounded off to the single decimal point. (NCT03439293)
Timeframe: Up to data cut-off: 1 January 2022 (Approximately 4 years)

Interventionpercentage of participants (Number)
Ixazomib 4 mg + Daratumumab 16 mg/kg + Dexamethasone 20 mg66.1

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Duration of Response (DOR)

DOR is defined as the time from the date of first documentation of PR or better to the date of the first documented PD among participants who responded to the treatment. (NCT03439293)
Timeframe: Up to data cut-off: 1 January 2022 (Up to approximately 4 years)

Interventionmonths (Median)
Ixazomib 4 mg + Daratumumab 16 mg/kg + Dexamethasone 20 mg24.0

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Time To Response (TTR)

TTR is defined as the time from first dose of any study drug treatment to the date of first documentation of PR or better. PR is defined as >=50% reduction of serum M protein and reduction in 24-hour urinary M protein by >=90%/to <200 mg/24 hours; In addition, if present at baseline, >=50% reduction in size of soft tissue plasmacytomas; no known evidence of progressive/new bone lesions. (NCT03439293)
Timeframe: Up to data cut-off: 1 January 2022 (Approximately 4 years)

Interventionmonths (Median)
Ixazomib 4 mg + Daratumumab 16 mg/kg + Dexamethasone 20 mgNA

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>= Very Good Partial Response (VGPR) Response Percentage With Pembrolizumab Added to Ixazomib Citrate and Dexamethasone

Will be estimated by the number of patients who achieve a VGPR, complete response (CR), or stringent complete response (sCR) at any time divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success rate will be calculated. (NCT03506360)
Timeframe: Up to 9 months

Interventionpercentage of responders (Number)
Treatment (Ixazomib Citrate, Pembrolizumab, and Dexamethasone)0

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Complete Response Percentage With Pembrolizumab Added to Ixazomib Citrate and Dexamethasone

Will be estimated by the number of patients who achieve a CR or sCR at any time divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success rate will be calculated. (NCT03506360)
Timeframe: Up to 2 years

Interventionpercentage of responders (Number)
Treatment (Ixazomib Citrate, Pembrolizumab, and Dexamethasone)0

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Incidence of Adverse Events

Graded according National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. (NCT03506360)
Timeframe: Up to 9 months

InterventionParticipants (Count of Participants)
Treatment (Ixazomib Citrate, Pembrolizumab, and Dexamethasone)13

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Overall Response Percentage

Defined as a partial response or better noted as the objective status on two consecutive evaluations. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner. (NCT03506360)
Timeframe: Up to 9 months

Interventionpercentage of responders (Number)
Treatment (Ixazomib Citrate, Pembrolizumab, and Dexamethasone)0.077

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Survival Time

The distribution of survival time will be estimated using the method of Kaplan-Meier. (NCT03506360)
Timeframe: Up to 2 years

InterventionMonths (Median)
Treatment (Ixazomib Citrate, Pembrolizumab, and Dexamethasone)9

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Progression-free Survival

The distribution of progression-free survival will be estimated using the method of Kaplan-Meier. (NCT03506360)
Timeframe: Up to 2 years

InterventionMonths (Median)
Treatment (Ixazomib Citrate, Pembrolizumab, and Dexamethasone)1.6

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Number of Participants Experiencing a Dose Limiting Toxicity (Dose Escalation)

Number of participants experiencing a dose limiting toxicity to determine the maximum tolerated dose (MTD) (NCT03770260)
Timeframe: At Day 28

,,
InterventionParticipants (Count of Participants)
Experienced a Dose Limiting ToxicityDid Not Experience a Dose Limiting ToxicityWithdrew from Treatment
Dose Level 1030
Dose Level 2031
Dose Level 3010

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Objective Response Rate (ORR)

"ORR is defined as percentage of participants with complete response (CR) and partial response (PR) per International Myeloma Working Group (IMWG) criteria below.~CR = Negative immunofixation on serum and urine; disappearance of soft tissue plasmacytomas, and <5% plasma cells in bone marrow~Stringent CR = Above definition plus normal FLC ration and absence of clonal cells in bone marrow by IHC or 2-4 color flow cytometry~PR = At least 50% reduction of serum M-protein and reduction in 24 urinary M-protein by at least 90% or to <200 mg/24 h. If serum and urine M-protein unmeasurable, require at least 50% decrease in difference between involved and uninvolved FLC levels. If serum free light assay also unmeasurable, require at least 50% reduction in plasma cells, provided baseline was at least 30%~Very Good PR (VGPR) = Serum and urine M-protein detectable by immunofixation but not on electrophoresis, or >90% reduction in serum M-protein plus urine M-protein level <100 mg/24 h" (NCT04119336)
Timeframe: up to 8 months

Interventionpercentage of participants (Number)
Nivolumab and Ixazomib0

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Progression Free Survival

"Progression-free survival (PFS) is defined as the time from starting study treatment to disease progression or death from any cause. The International Myeloma Working Group (IMWG) criteria defines progressive disease (PD) as at least 25% increase from lowest response value of any of the following:~Serum M-component (absolute increase must be at least 0.5 g/dL)~Urine M-component (absolute increase must be at least 200 mg/24 h)~If serum and urine M-protein unmeasurable, absolute increase in free light chain (FLC) must be >10 mg/dL. If FLC levels also unmeasurable, absolute increase in bone marrow plasma cell percentage must be at least 10%.~Definite development of new bone lesions or soft tissue plasmacytomas, or definite increase in size of existing bone lesions or soft tissue plasmacytomas~Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to the plasma cell proliferative disorder" (NCT04119336)
Timeframe: Up to 2 years

Interventionmonths (Median)
Nivolumab and Ixazomib3.96

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Number of Participants With Grade 3 or Higher Laboratory Tests Abnormalities

Laboratory tests abnormalities were graded using the CTCAE version 4.03. as: Grade 1 (Mild, asymptomatic or mild symptoms); Grade 2 (Moderate, minimal, local or noninvasive intervention indicated); Grade 3 (Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated); Grade 4 (Life-threatening consequences, urgent intervention indicated); Grade 5 (Death related to AE). (NCT04272775)
Timeframe: Baseline up to 29 days after last dose of study drug (up to Cycle 87 Day 44) (Each Cycle length=28 days)

,
InterventionParticipants (Count of Participants)
Grade 4: Neutrophils lowGrade 4: Leukocytes lowGrade 4: Lymphocytes lowGrade 4: Platelets lowGrade 4: Sodium lowGrade 4: Potassium lowGrade 3: Neutrophils lowGrade 3: Hemoglobin lowGrade 3: Leukocytes lowGrade 3: Lymphocytes lowGrade 3: Platelets lowGrade 3: Albumin lowGrade 3: Corrected calcium highGrade 3: Sodium lowGrade 3: Potassium lowGrade 3: Phosphate low
Cohort 1: Ixazomib 4.0 mg0033004233010111
Cohort 2: Ixazomib 4.0 mg + Lenalidomide and Dexamethasone2102112223211001

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Number of Participants Who Achieved Complete Response (CR), Very Good Partial Response (VGPR), and Partial Response (PR)

Number of participants who achieved CR, PR, VGPR were assessed in accordance to International Myeloma Working Group Uniform Response Criteria for Multiple Myeloma. CR: No immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and <5% plasma cells in bone marrow. Normal serum free light chain (SFLC) ratio if disease measurable only by SFLC. VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or greater than or equal to (>=) 90% decrease in serum M-protein with urine M-protein <100 milligram per 24 hours (mg/24 hrs). If disease measurable only by SFLC, >= 90% decrease in the difference between involved and uninvolved FLC levels (dFLC). PR: >= 50% reduction of serum M-protein and >= 90% reduction in urine M-protein or to <200 mg/24 hrs, or a >= 50% decrease in dFLC. A >=50% decrease in the size of soft tissue plasmacytomas present at baseline (NCT04272775)
Timeframe: Baseline up to 29 days after last dose of study drug (up to Cycle 87 Day 44) (Each Cycle length=28 days)

InterventionParticipants (Count of Participants)
Cohort 1: Ixazomib 4.0 mg0
Cohort 2: Ixazomib 4.0 mg + Lenalidomide and Dexamethasone2

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Number of Participants Who Experienced at Least One Treatment-emergent Adverse Event (TEAE)

(NCT04272775)
Timeframe: Baseline up to 29 days after last dose of study drug (up to Cycle 87 Day 44) (Each Cycle length=28 days)

InterventionParticipants (Count of Participants)
Cohort 1: Ixazomib 4.0 mg7
Cohort 2: Ixazomib 4.0 mg + Lenalidomide and Dexamethasone7

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Number of Participants With Grade 3 or Higher TEAE Related to Body Weight

Body weight abnormalities were graded using the CTCAE version 4.03. as: Grade 1 (Mild, asymptomatic or mild symptoms); Grade 2 (Moderate, minimal, local or noninvasive intervention indicated); Grade 3 (Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated); Grade 4 (Life-threatening consequences, urgent intervention indicated); Grade 5 (Death related to AE). (NCT04272775)
Timeframe: Baseline up to 29 days after last dose of study drug (up to Cycle 87 Day 44) (Each Cycle length=28 days)

InterventionParticipants (Count of Participants)
Cohort 1: Ixazomib 4.0 mg0
Cohort 2: Ixazomib 4.0 mg + Lenalidomide and Dexamethasone0

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Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)

DLT:Any following adverse events (AEs) possibly related to ixazomib assessed by Common Terminology Criteria for AEs (CTCAE) version 4.03; Grade 4 neutropenia/thrombocytopenia lasting >7 consecutive days; Grade 3/greater neutropenia with fever/infections; Grade 3/greater thrombocytopenia with clinically significant bleeding; platelet count less than (<)10,000 per cubic meter(/mm^3); Grade 2 peripheral neuropathy with pain/Grade 3 or greater peripheral neuropathy; Grade 3/greater nonhematologic toxicities with exceptions of arthralgia/myalgia, fatigue lasting <7 days manageable nausea/emesis with antiemetic prophylaxis, diarrhea that is controlled with supportive care; treatment delay of >14 days at start of Cycle 2 due to failure of hematologic/nonhematologic recovery; Other Grade 2/greater ixazomib related nonhematologic toxicities required permanent discontinuation of ixazomib;Inability to receive at least 80% of planned lenalidomide doses due to the AEs related to ixazomib. (NCT04272775)
Timeframe: From Cycle 1 Day 1 until Cycle 2 Day 1 (Cycle length is equal to [=] 28 days)

InterventionParticipants (Count of Participants)
Cohort 1: Ixazomib 4.0 mg1
Cohort 2: Ixazomib 4.0 mg + Lenalidomide and Dexamethasone1

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Cmax: Maximum Observed Plasma Concentration for Ixazomib

(NCT04272775)
Timeframe: Days 1 and 15 of Cycle 1: pre-dose and at multiple time points (15, 30, 60, and 90 minutes and 2, 4, 8, 24, 48, 96, and 168 hours) post-dose (Cycle length=28 days)

,
Interventionnanogram per milliliter (ng/mL) (Geometric Mean)
Day 1Day 15
Cohort 1: Ixazomib 4.0 mg65.368.8
Cohort 2: Ixazomib 4.0 mg + Lenalidomide and Dexamethasone32.934.5

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SubstanceRelationship StrengthStudiesTrialsClassesRoles
3-phenylpropionic acid
3-phenylpropionic acid: RN given refers to parent cpd. 3-phenylpropionic acid : A monocarboxylic acid that is propionic acid substituted at position 3 by a phenyl group.		2.2510benzenes;
monocarboxylic acid		antifungal agent;
human metabolite;
plant metabolite
aminolevulinic acid
Aminolevulinic Acid: A compound produced from succinyl-CoA and GLYCINE as an intermediate in heme synthesis. It is used as a PHOTOCHEMOTHERAPY for actinic KERATOSIS.. 5-aminolevulinic acid : The simplest delta-amino acid in which the hydrogens at the gamma position are replaced by an oxo group. It is metabolised to protoporphyrin IX, a photoactive compound which accumulates in the skin. Used (in the form of the hydrochloride salt)in combination with blue light illumination for the treatment of minimally to moderately thick actinic keratosis of the face or scalp.		2.6104-oxo monocarboxylic acid;
amino acid zwitterion;
delta-amino acid		antineoplastic agent;
dermatologic drug;
Escherichia coli metabolite;
human metabolite;
mouse metabolite;
photosensitizing agent;
plant metabolite;
prodrug;
Saccharomyces cerevisiae metabolite
chlorine
chloride : A halide anion formed when chlorine picks up an electron to form an an anion.		2.110halide anion;
monoatomic chlorine		cofactor;
Escherichia coli metabolite;
human metabolite
coumarin
2H-chromen-2-one: coumarin derivative		2.610coumarinsfluorescent dye;
human metabolite;
plant metabolite
salicylic acid
Scalp: The outer covering of the calvaria. It is composed of several layers: SKIN; subcutaneous connective tissue; the occipitofrontal muscle which includes the tendinous galea aponeurotica; loose connective tissue; and the pericranium (the PERIOSTEUM of the SKULL).		2.610monohydroxybenzoic acidalgal metabolite;
antifungal agent;
antiinfective agent;
EC 1.11.1.11 (L-ascorbate peroxidase) inhibitor;
keratolytic drug;
plant hormone;
plant metabolite
glycine
[no description available]		21.225276alpha-amino acid;
amino acid zwitterion;
proteinogenic amino acid;
serine family amino acid		EC 2.1.2.1 (glycine hydroxymethyltransferase) inhibitor;
fundamental metabolite;
hepatoprotective agent;
micronutrient;
neurotransmitter;
NMDA receptor agonist;
nutraceutical
indoleacetic acid
indoleacetic acid: RN given refers to unlabeled parent cpd; structure in Merck Index, 9th ed, #4841. auxin : Any of a group of compounds, both naturally occurring and synthetic, that induce cell elongation in plant stems (from Greek alphaupsilonxialphanuomega, "to grow").. indole-3-acetic acid : A monocarboxylic acid that is acetic acid in which one of the methyl hydrogens has been replaced by a 1H-indol-3-yl group.		2.2510indole-3-acetic acids;
monocarboxylic acid		auxin;
human metabolite;
mouse metabolite;
plant hormone;
plant metabolite
thioctic acid
Thioctic Acid: An octanoic acid bridged with two sulfurs so that it is sometimes also called a pentanoic acid in some naming schemes. It is biosynthesized by cleavage of LINOLEIC ACID and is a coenzyme of oxoglutarate dehydrogenase (KETOGLUTARATE DEHYDROGENASE COMPLEX). It is used in DIETARY SUPPLEMENTS.		2.610dithiolanes;
heterocyclic fatty acid;
thia fatty acid		fundamental metabolite;
geroprotector
niacin
Niacin: A water-soluble vitamin of the B complex occurring in various animal and plant tissues. It is required by the body for the formation of coenzymes NAD and NADP. It has PELLAGRA-curative, vasodilating, and antilipemic properties.. vitamin B3 : Any member of a group of vitamers that belong to the chemical structural class called pyridines that exhibit biological activity against vitamin B3 deficiency. Vitamin B3 deficiency causes a condition known as pellagra whose symptoms include depression, dermatitis and diarrhea. The vitamers include nicotinic acid and nicotinamide (and their ionized and salt forms).. nicotinic acid : A pyridinemonocarboxylic acid that is pyridine in which the hydrogen at position 3 is replaced by a carboxy group.		2.2510pyridine alkaloid;
pyridinemonocarboxylic acid;
vitamin B3		antidote;
antilipemic drug;
EC 3.5.1.19 (nicotinamidase) inhibitor;
Escherichia coli metabolite;
human urinary metabolite;
metabolite;
mouse metabolite;
plant metabolite;
vasodilator agent
phosphorylcholine
Phosphorylcholine: Calcium and magnesium salts used therapeutically in hepatobiliary dysfunction.. phosphocholine : The phosphate of choline; and the parent compound of the phosphocholine family.		3.1910phosphocholinesallergen;
epitope;
hapten;
human metabolite;
mouse metabolite
picolinic acid
picolinic acid: iron-chelating agent that inhibits DNA synthesis; may interfere with iron-dependent production of stable free organic radical which is essential for ribonucleotide reductase formation of deoxyribonucleotides; RN given refers to parent cpd; structure in Merck Index, 9th ed, #7206. picolinic acid : A pyridinemonocarboxylic acid in which the carboxy group is located at position 2. It is an intermediate in the metabolism of tryptophan.		2.7620pyridinemonocarboxylic acidhuman metabolite;
MALDI matrix material
pyrazinoic acid
pyrazinoic acid: active metabolite of pyrazinamide; structure. pyrazine-2-carboxylic acid : The parent compound of the class of pyrazinecarboxylic acids, that is pyrazine bearing a single carboxy substituent. The active metabolite of the antitubercular drug pyrazinamide.		2.2510pyrazinecarboxylic acidantitubercular agent;
drug metabolite
thiamine
thiamine(1+) : A primary alcohol that is 1,3-thiazol-3-ium substituted by (4-amino-2-methylpyrimidin-5-yl)methyl, methyl and 2-hydroxyethyl groups at positions 3, 4 and 5, respectively.		2.610primary alcohol;
vitamin B1		Escherichia coli metabolite;
human metabolite;
mouse metabolite;
Saccharomyces cerevisiae metabolite
pk 11195
PK-11195 : A monocarboxylic acid amide obtained by formal condensation of the carboxy group of 1-(2-chlorophenyl)isoquinoline-3-carboxylic acid with the amino group of sec-butylmethylamine		2.0810aromatic amide;
isoquinolines;
monocarboxylic acid amide;
monochlorobenzenes		antineoplastic agent
pd 173074
[no description available]		2.0810aromatic amine;
biaryl;
dimethoxybenzene;
pyridopyrimidine;
tertiary amino compound;
ureas		antineoplastic agent;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor;
fibroblast growth factor receptor antagonist
3-aminobenzamide
[no description available]		2.610benzamides;
substituted aniline		EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor
pleconaril
WIN 63843: structure given in first source		2.610
4-(2-aminoethyl)benzenesulfonylfluoride
[no description available]		2.610
phenytoin
[no description available]		2.610imidazolidine-2,4-dioneanticonvulsant;
drug allergen;
sodium channel blocker;
teratogenic agent
abt 702
[no description available]		2.0810bipyridines
acetazolamide
Acetazolamide: One of the CARBONIC ANHYDRASE INHIBITORS that is sometimes effective against absence seizures. It is sometimes useful also as an adjunct in the treatment of tonic-clonic, myoclonic, and atonic seizures, particularly in women whose seizures occur or are exacerbated at specific times in the menstrual cycle. However, its usefulness is transient often because of rapid development of tolerance. Its antiepileptic effect may be due to its inhibitory effect on brain carbonic anhydrase, which leads to an increased transneuronal chloride gradient, increased chloride current, and increased inhibition. (From Smith and Reynard, Textbook of Pharmacology, 1991, p337)		2.6620monocarboxylic acid amide;
sulfonamide;
thiadiazoles		anticonvulsant;
diuretic;
EC 4.2.1.1 (carbonic anhydrase) inhibitor
alprenolol
Alprenolol: One of the ADRENERGIC BETA-ANTAGONISTS used as an antihypertensive, anti-anginal, and anti-arrhythmic agent.. alprenolol : A secondary alcohol that is propan-2-ol substituted by a 2-allylphenoxy group at position 1 and an isopropylamino group at position 3. It is a beta-adrenergic antagonist used as a antihypertensive, anti-arrhythmia and a sympatholytic agent.		2.610secondary alcohol;
secondary amino compound		anti-arrhythmia drug;
antihypertensive agent;
beta-adrenergic antagonist;
sympatholytic agent
amantadine
amant: an antiviral compound consisting of an adamantane derivative chemically linked to a water-solube polyanioic matrix; structure in first source		2.610adamantanes;
primary aliphatic amine		analgesic;
antiparkinson drug;
antiviral drug;
dopaminergic agent;
NMDA receptor antagonist;
non-narcotic analgesic
2-aminothiazole
2-aminothiazole: RN given refers to parent cpd; structure. 1,3-thiazol-2-amine : A primary amino compound that is 1,3-thiazole substituted by an amino group at position 2.		2.6101,3-thiazoles;
primary amino compound
amodiaquine
Amodiaquine: A 4-aminoquinoline compound with anti-inflammatory properties.. amodiaquine : A quinoline having a chloro group at the 7-position and an aryl amino group at the 4-position.		2.610aminoquinoline;
organochlorine compound;
phenols;
secondary amino compound;
tertiary amino compound		anticoronaviral agent;
antimalarial;
drug allergen;
EC 2.1.1.8 (histamine N-methyltransferase) inhibitor;
non-steroidal anti-inflammatory drug;
prodrug
aspirin
Aspirin: The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5). acetylsalicylate : A benzoate that is the conjugate base of acetylsalicylic acid, arising from deprotonation of the carboxy group.. acetylsalicylic acid : A member of the class of benzoic acids that is salicylic acid in which the hydrogen that is attached to the phenolic hydroxy group has been replaced by an acetoxy group. A non-steroidal anti-inflammatory drug with cyclooxygenase inhibitor activity.		2.610benzoic acids;
phenyl acetates;
salicylates		anticoagulant;
antipyretic;
cyclooxygenase 1 inhibitor;
cyclooxygenase 2 inhibitor;
drug allergen;
EC 1.1.1.188 (prostaglandin-F synthase) inhibitor;
geroprotector;
non-narcotic analgesic;
non-steroidal anti-inflammatory drug;
plant activator;
platelet aggregation inhibitor;
prostaglandin antagonist;
teratogenic agent
baclofen
[no description available]		2.610amino acid zwitterion;
gamma-amino acid;
monocarboxylic acid;
monochlorobenzenes;
primary amino compound		central nervous system depressant;
GABA agonist;
muscle relaxant
benzamide
benzamide : An aromatic amide that consists of benzene bearing a single carboxamido substituent. The parent of the class of benzamides.		2.610benzamides
bicalutamide
bicalutamide: approved for treatment of advanced prostate cancer. N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide : A member of the class of (trifluoromethyl)benzenes that is 4-amino-2-(trifluoromethyl)benzonitrile in which one of the amino hydrogens is substituted by a 3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanoyl group.. bicalutamide : A racemate comprising of equal amounts of (R)-bicalutamide and (S)-bicalutamide. It is an oral non-steroidal antiandrogen used in the treatment of prostate cancer and hirsutism.		2.0810(trifluoromethyl)benzenes;
monocarboxylic acid amide;
monofluorobenzenes;
nitrile;
sulfone;
tertiary alcohol
verapamil
Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent.. verapamil : A racemate comprising equimolar amounts of dexverapamil and (S)-verapamil. An L-type calcium channel blocker of the phenylalkylamine class, it is used (particularly as the hydrochloride salt) in the treatment of hypertension, angina pectoris and cardiac arrhythmia, and as a preventive medication for migraine.. 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile : A tertiary amino compound that is 3,4-dimethoxyphenylethylamine in which the hydrogens attached to the nitrogen are replaced by a methyl group and a 4-cyano-4-(3,4-dimethoxyphenyl)-5-methylhexyl group.		2.0810aromatic ether;
nitrile;
polyether;
tertiary amino compound
camostat
camostat : A benzoate ester resulting from the formal condensation of the carboxy group of 4-guanidinobenzoic acid with the hydroxy group of 2-(dimethylamino)-2-oxoethyl (4-hydroxyphenyl)acetate. It is a potent inhibitor of the human transmembrane protease serine 2 (TMPRSS2) and its mesylate salt is currently under investigation for its effectiveness in COVID-19 patients.		2.610benzoate ester;
carboxylic ester;
diester;
guanidines;
tertiary carboxamide		anti-inflammatory agent;
anticoronaviral agent;
antifibrinolytic drug;
antihypertensive agent;
antineoplastic agent;
antiviral agent;
serine protease inhibitor
camphor, (+-)-isomer
[no description available]		2.610bornane monoterpenoid;
cyclic monoterpene ketone		plant metabolite
candesartan
candesartan: a nonpeptide angiotensin II receptor antagonist. candesartan : A benzimidazolecarboxylic acid that is 1H-benzimidazole-7-carboxylic acid substituted by an ethoxy group at position 2 and a ({2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl}methyl) group at position 1. It is a angiotensin receptor antagonist used for the treatment of hypertension.		2.610benzimidazolecarboxylic acid;
biphenylyltetrazole		angiotensin receptor antagonist;
antihypertensive agent;
environmental contaminant;
xenobiotic
celecoxib
[no description available]		2.0810organofluorine compound;
pyrazoles;
sulfonamide;
toluenes		cyclooxygenase 2 inhibitor;
geroprotector;
non-narcotic analgesic;
non-steroidal anti-inflammatory drug
cetylpyridinium
Cetylpyridinium: Cationic bactericidal surfactant used as a topical antiseptic for skin, wounds, mucous membranes, instruments, etc.; and also as a component in mouthwash and lozenges.		2.610pyridinium ion
chelerythrine
chelerythrine : A benzophenanthridine alkaloid isolated from the root of Zanthoxylum simulans, Chelidonium majus L., and other Papaveraceae.		2.0810benzophenanthridine alkaloid;
organic cation		antibacterial agent;
antineoplastic agent;
EC 2.7.11.13 (protein kinase C) inhibitor
chloroxylenol
chloroxylenol: topical antiseptic; RN given refers to parent cpd; structure. 4-chloro-3,5-dimethylphenol : A member of the class of phenols that is 3,5-xylenol which is substituted at position 4 by chlorine. It is bactericidal against most Gram-positive bacteria but less effective against Staphylococci and Gram-negative bacteria, and often inactive against Pseudomonas species. It is ineffective against bacterial spores.		2.610monochlorobenzenes;
phenols		antiseptic drug;
disinfectant;
molluscicide
chlorpromazine
Chlorpromazine: The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class chlorpromazine's antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking DOPAMINE RECEPTORS. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup.. chlorpromazine : A substituted phenothiazine in which the ring nitrogen at position 10 is attached to C-3 of an N,N-dimethylpropanamine moiety.		2.610organochlorine compound;
phenothiazines;
tertiary amine		anticoronaviral agent;
antiemetic;
dopaminergic antagonist;
EC 3.4.21.26 (prolyl oligopeptidase) inhibitor;
phenothiazine antipsychotic drug
ciprofibrate
[no description available]		2.610cyclopropanes;
monocarboxylic acid;
organochlorine compound		antilipemic drug
clomipramine
Clomipramine: A tricyclic antidepressant similar to IMIPRAMINE that selectively inhibits the uptake of serotonin in the brain. It is readily absorbed from the gastrointestinal tract and demethylated in the liver to form its primary active metabolite, desmethylclomipramine.. clomipramine : A dibenzoazepine that is 10,11-dihydro-5H-dibenzo[b,f]azepine which is substituted by chlorine at position 3 and in which the hydrogen attached to the nitrogen is replaced by a 3-(dimethylamino)propyl group. One of the more sedating tricyclic antidepressants, it is used as the hydrochloride salt for the treatment of depression as well as obsessive-compulsive disorder and phobias.		2.610dibenzoazepineanticoronaviral agent;
antidepressant;
EC 1.8.1.12 (trypanothione-disulfide reductase) inhibitor;
serotonergic antagonist;
serotonergic drug;
serotonin uptake inhibitor
danthron
danthron: structure. chrysazin : A dihydroxyanthraquinone that is anthracene-9,10-dione substituted by hydroxy groups at positions 1 and 8.		2.610dihydroxyanthraquinoneapoptosis inducer;
plant metabolite
deferiprone
Deferiprone: A pyridone derivative and iron chelator that is used in the treatment of IRON OVERLOAD in patients with THALASSEMIA.. deferiprone : A member of the class of 4-pyridones that is pyridin-4(1H)-one substituted at positions 1 and 2 by methyl groups and at position 3 by a hydroxy group. A lipid-soluble iron-chelator used for treatment of thalassaemia.		2.6104-pyridonesiron chelator;
protective agent
dipyridamole
Dipyridamole: A phosphodiesterase inhibitor that blocks uptake and metabolism of adenosine by erythrocytes and vascular endothelial cells. Dipyridamole also potentiates the antiaggregating action of prostacyclin. (From AMA Drug Evaluations Annual, 1994, p752). dipyridamole : A pyrimidopyrimidine that is 2,2',2'',2'''-(pyrimido[5,4-d]pyrimidine-2,6-diyldinitrilo)tetraethanol substituted by piperidin-1-yl groups at positions 4 and 8 respectively. A vasodilator agent, it inhibits the formation of blood clots.		2.610piperidines;
pyrimidopyrimidine;
tertiary amino compound;
tetrol		adenosine phosphodiesterase inhibitor;
EC 3.5.4.4 (adenosine deaminase) inhibitor;
platelet aggregation inhibitor;
vasodilator agent
disulfiram
[no description available]		2.610organic disulfide;
organosulfur acaricide		angiogenesis inhibitor;
antineoplastic agent;
apoptosis inducer;
EC 1.2.1.3 [aldehyde dehydrogenase (NAD(+))] inhibitor;
EC 3.1.1.1 (carboxylesterase) inhibitor;
EC 3.1.1.8 (cholinesterase) inhibitor;
EC 5.99.1.2 (DNA topoisomerase) inhibitor;
ferroptosis inducer;
fungicide;
NF-kappaB inhibitor
valproic acid
Valproic Acid: A fatty acid with anticonvulsant and anti-manic properties that is used in the treatment of EPILEPSY and BIPOLAR DISORDER. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of VOLTAGE-GATED SODIUM CHANNELS.. valproic acid : A branched-chain saturated fatty acid that comprises of a propyl substituent on a pentanoic acid stem.		3.9220branched-chain fatty acid;
branched-chain saturated fatty acid		anticonvulsant;
antimanic drug;
EC 3.5.1.98 (histone deacetylase) inhibitor;
GABA agent;
neuroprotective agent;
psychotropic drug;
teratogenic agent
doxazosin
Doxazosin: A prazosin-related compound that is a selective alpha-1-adrenergic blocker.. doxazosin : A member of the class of quinazolines that is quinazoline substituted by an amino group at position 4, methoxy groups at positions 6 and 7 and a piperazin-1-yl group at position 2 which in turn is substituted by a 2,3-dihydro-1,4-benzodioxin-2-ylcarbonyl group at position 4. An antihypertensive agent, it is used in the treatment of high blood pressure.		2.610aromatic amine;
benzodioxine;
monocarboxylic acid amide;
N-acylpiperazine;
N-arylpiperazine;
quinazolines		alpha-adrenergic antagonist;
antihyperplasia drug;
antihypertensive agent;
antineoplastic agent;
vasodilator agent
ebselen
ebselen : A benzoselenazole that is 1,2-benzoselenazol-3-one carrying an additional phenyl substituent at position 2. Acts as a mimic of glutathione peroxidase.		2.610benzoselenazoleanti-inflammatory drug;
antibacterial agent;
anticoronaviral agent;
antifungal agent;
antineoplastic agent;
antioxidant;
apoptosis inducer;
EC 1.13.11.33 (arachidonate 15-lipoxygenase) inhibitor;
EC 1.13.11.34 (arachidonate 5-lipoxygenase) inhibitor;
EC 1.3.1.8 [acyl-CoA dehydrogenase (NADP(+))] inhibitor;
EC 1.8.1.12 (trypanothione-disulfide reductase) inhibitor;
EC 2.5.1.7 (UDP-N-acetylglucosamine 1-carboxyvinyltransferase) inhibitor;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor;
EC 3.1.3.25 (inositol-phosphate phosphatase) inhibitor;
EC 3.4.22.69 (SARS coronavirus main proteinase) inhibitor;
EC 3.5.4.1 (cytosine deaminase) inhibitor;
EC 5.1.3.2 (UDP-glucose 4-epimerase) inhibitor;
enzyme mimic;
ferroptosis inhibitor;
genotoxin;
hepatoprotective agent;
neuroprotective agent;
radical scavenger
etidronate
Etidronic Acid: A diphosphonate which affects calcium metabolism. It inhibits ectopic calcification and slows down bone resorption and bone turnover.. etidronic acid : A 1,1-bis(phosphonic acid) that is (ethane-1,1-diyl)bis(phosphonic acid) having a hydroxy substituent at the 1-position. It inhibits the formation, growth, and dissolution of hydroxyapatite crystals by chemisorption to calcium phosphate surfaces.		2.6101,1-bis(phosphonic acid)antineoplastic agent;
bone density conservation agent;
chelator
2-hexyloxybenzamide
2-hexyloxybenzamide: structure		2.610aromatic ether;
benzamides		antifungal agent
brl 42810
[no description available]		2.6102-aminopurines;
acetate ester		antiviral drug;
prodrug
fluphenazine
[no description available]		2.610N-alkylpiperazine;
organofluorine compound;
phenothiazines		anticoronaviral agent;
dopaminergic antagonist;
phenothiazine antipsychotic drug
fluorouracil
Fluorouracil: A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid.. 5-fluorouracil : A nucleobase analogue that is uracil in which the hydrogen at position 5 is replaced by fluorine. It is an antineoplastic agent which acts as an antimetabolite - following conversion to the active deoxynucleotide, it inhibits DNA synthesis (by blocking the conversion of deoxyuridylic acid to thymidylic acid by the cellular enzyme thymidylate synthetase) and so slows tumour growth.		2.610nucleobase analogue;
organofluorine compound		antimetabolite;
antineoplastic agent;
environmental contaminant;
immunosuppressive agent;
radiosensitizing agent;
xenobiotic
furosemide
Furosemide: A benzoic-sulfonamide-furan. It is a diuretic with fast onset and short duration that is used for EDEMA and chronic RENAL INSUFFICIENCY.. furosemide : A chlorobenzoic acid that is 4-chlorobenzoic acid substituted by a (furan-2-ylmethyl)amino and a sulfamoyl group at position 2 and 5 respectively. It is a diuretic used in the treatment of congestive heart failure.		2.0810chlorobenzoic acid;
furans;
sulfonamide		environmental contaminant;
loop diuretic;
xenobiotic
gabexate
Gabexate: A serine proteinase inhibitor used therapeutically in the treatment of pancreatitis, disseminated intravascular coagulation (DIC), and as a regional anticoagulant for hemodialysis. The drug inhibits the hydrolytic effects of thrombin, plasmin, and kallikrein, but not of chymotrypsin and aprotinin.		2.7620benzoate ester
glutaral
Glutaral: One of the protein CROSS-LINKING REAGENTS that is used as a disinfectant for sterilization of heat-sensitive equipment and as a laboratory reagent, especially as a fixative.. glutaraldehyde : A dialdehyde comprised of pentane with aldehyde functions at C-1 and C-5.		2.610dialdehydecross-linking reagent;
disinfectant;
fixative
gossypol
Gossypol: A dimeric sesquiterpene found in cottonseed (GOSSYPIUM). The (-) isomer is active as a male contraceptive (CONTRACEPTIVE AGENTS, MALE) whereas toxic symptoms are associated with the (+) isomer.		2.4920
fasudil
fasudil: intracellular calcium antagonist; structure in first source. fasudil : An isoquinoline substituted by a (1,4-diazepan-1-yl)sulfonyl group at position 5. It is a Rho-kinase inhibitor and its hydrochloride hydrate form is approved for the treatment of cerebral vasospasm and cerebral ischemia.		2.5820isoquinolines;
N-sulfonyldiazepane		antihypertensive agent;
calcium channel blocker;
EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor;
geroprotector;
neuroprotective agent;
nootropic agent;
vasodilator agent
haloperidol
Haloperidol: A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279). haloperidol : A compound composed of a central piperidine structure with hydroxy and p-chlorophenyl substituents at position 4 and an N-linked p-fluorobutyrophenone moiety.		2.610aromatic ketone;
hydroxypiperidine;
monochlorobenzenes;
organofluorine compound;
tertiary alcohol		antidyskinesia agent;
antiemetic;
dopaminergic antagonist;
first generation antipsychotic;
serotonergic antagonist
hexachlorophene
Hexachlorophene: A chlorinated bisphenol antiseptic with a bacteriostatic action against Gram-positive organisms, but much less effective against Gram-negative organisms. It is mainly used in soaps and creams and is an ingredient of various preparations used for skin disorders. (From Martindale, The Extra Pharmacopoeia, 30th ed, p797). hexachlorophene : An organochlorine compound that is diphenylmethane in which each of the phenyl groups is substituted by chlorines at positions 2, 3, and 5, and by a hydroxy group at position 6. An antiseptic that is effective against Gram-positive organisms, it is used in soaps and creams for the treatment of various skin disorders. It is also used in agriculture as an acaricide and fungicide, but is not approved for such use within the European Union.		2.2510bridged diphenyl fungicide;
polyphenol;
trichlorobenzene		acaricide;
antibacterial agent;
antifungal agrochemical;
antiseptic drug
miltefosine
miltefosine: hexadecyl phosphocholine derivative of cisplatin; did not substantially activate HIV long terminal repeat; less toxic than cisplatin. miltefosine : A phospholipid that is the hexadecyl monoester of phosphocholine.		2.610phosphocholines;
phospholipid		anti-inflammatory agent;
anticoronaviral agent;
antifungal agent;
antineoplastic agent;
antiprotozoal drug;
apoptosis inducer;
immunomodulator;
protein kinase inhibitor
hexylresorcinol
[no description available]		2.610resorcinols
beta-thujaplicin
beta-thujaplicin: structure. beta-thujaplicin : A monoterpenoid that is cyclohepta-2,4,6-trien-1-one substituted by a hydroxy group at position 2 and an isopropyl group at position 4. Isolated from Thuja plicata and Chamaecyparis obtusa, it exhibits antimicrobial activities.		2.610cyclic ketone;
enol;
monoterpenoid		antibacterial agent;
antifungal agent;
antineoplastic agent;
antiplasmodial drug;
plant metabolite
hycanthone
Hycanthone: Potentially toxic, but effective antischistosomal agent, it is a metabolite of LUCANTHONE.. hycanthone : A thioxanthen-9-one compound having a hydroxymethyl substituent at the 1-position and a 2-[(diethylamino)ethyl]amino substituent at the 4-position. It was formerly used (particularly as the monomethanesulfonic acid salt) as a schistosomicide for individual or mass treatement of infection with Schistosoma haematobium and S. mansoni, but due to its toxicity and concern about possible carcinogenicity, it has been replaced by other drugs such as praziquantel.		2.610thioxanthenesmutagen;
schistosomicide drug
hydrochlorothiazide
Hydrochlorothiazide: A thiazide diuretic often considered the prototypical member of this class. It reduces the reabsorption of electrolytes from the renal tubules. This results in increased excretion of water and electrolytes, including sodium, potassium, chloride, and magnesium. It is used in the treatment of several disorders including edema, hypertension, diabetes insipidus, and hypoparathyroidism.. hydrochlorothiazide : A benzothiadiazine that is 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide substituted by a chloro group at position 6 and a sulfonamide at 7. It is diuretic used for the treatment of hypertension and congestive heart failure.		2.610benzothiadiazine;
organochlorine compound;
sulfonamide		antihypertensive agent;
diuretic;
environmental contaminant;
xenobiotic
hydroxyurea
[no description available]		2.610one-carbon compound;
ureas		antimetabolite;
antimitotic;
antineoplastic agent;
DNA synthesis inhibitor;
EC 1.17.4.1 (ribonucleoside-diphosphate reductase) inhibitor;
genotoxin;
immunomodulator;
radical scavenger;
teratogenic agent
ibuprofen
Midol: combination of cinnamedrine, phenacetin, aspirin & caffeine		2.7620monocarboxylic acidantipyretic;
cyclooxygenase 1 inhibitor;
cyclooxygenase 2 inhibitor;
drug allergen;
environmental contaminant;
geroprotector;
non-narcotic analgesic;
non-steroidal anti-inflammatory drug;
radical scavenger;
xenobiotic
indirubin-3'-monoxime
indirubin-3'-monoxime: has antiangiogenic activity. indirubin-3'-monoxime : A member of the class of biindoles that is indirubin in which the keto group at position 3' has undergone condensation with hydroxylamine to form the corresponding oxime.		2.0810
indomethacin
Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits CYCLOOXYGENASE, which is necessary for the formation of PROSTAGLANDINS and other AUTACOIDS. It also inhibits the motility of POLYMORPHONUCLEAR LEUKOCYTES.. indometacin : A member of the class of indole-3-acetic acids that is indole-3-acetic acid in which the indole ring is substituted at positions 1, 2 and 5 by p-chlorobenzoyl, methyl, and methoxy groups, respectively. A non-steroidal anti-inflammatory drug, it is used in the treatment of musculoskeletal and joint disorders including osteoarthritis, rheumatoid arthritis, gout, bursitis and tendinitis.		2.610aromatic ether;
indole-3-acetic acids;
monochlorobenzenes;
N-acylindole		analgesic;
drug metabolite;
EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor;
environmental contaminant;
gout suppressant;
non-steroidal anti-inflammatory drug;
xenobiotic metabolite;
xenobiotic
avapro
Irbesartan: A spiro compound, biphenyl and tetrazole derivative that acts as an angiotensin II type 1 receptor antagonist. It is used in the management of HYPERTENSION, and in the treatment of kidney disease.. irbesartan : A biphenylyltetrazole that is an angiotensin II receptor antagonist used mainly for the treatment of hypertension.		2.610azaspiro compound;
biphenylyltetrazole		angiotensin receptor antagonist;
antihypertensive agent;
environmental contaminant;
xenobiotic
itraconazole
[no description available]		2.610piperazines
ketoconazole
1-acetyl-4-(4-{[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazine : A dioxolane that is 1,3-dioxolane which is substituted at positions 2, 2, and 4 by imidazol-1-ylmethyl, 2,4-dichlorophenyl, and [para-(4-acetylpiperazin-1-yl)phenoxy]methyl groups, respectively.		4.4811dichlorobenzene;
dioxolane;
ether;
imidazoles;
N-acylpiperazine;
N-arylpiperazine
kojic acid
[no description available]		2.6104-pyranones;
enol;
primary alcohol		Aspergillus metabolite;
EC 1.10.3.1 (catechol oxidase) inhibitor;
EC 1.10.3.2 (laccase) inhibitor;
EC 1.13.11.24 (quercetin 2,3-dioxygenase) inhibitor;
EC 1.14.18.1 (tyrosinase) inhibitor;
EC 1.4.3.3 (D-amino-acid oxidase) inhibitor;
NF-kappaB inhibitor;
skin lightening agent
lansoprazole
Lansoprazole: A 2,2,2-trifluoroethoxypyridyl derivative of timoprazole that is used in the therapy of STOMACH ULCERS and ZOLLINGER-ELLISON SYNDROME. The drug inhibits H(+)-K(+)-EXCHANGING ATPASE which is found in GASTRIC PARIETAL CELLS. Lansoprazole is a racemic mixture of (R)- and (S)-isomers.		2.1510benzimidazoles;
pyridines;
sulfoxide		anti-ulcer drug;
EC 3.6.3.10 (H(+)/K(+)-exchanging ATPase) inhibitor
lapachol
lapachol : A hydroxy-1,4-naphthoquinone that is 1,4-naphthoquinone substituted by hydroxy and 3-methylbut-2-en-1-yl groups at positions 2 and 3, respectively. It is a natural compound that exhibits antibacterial and anticancer properties, first isolated in 1882 from the bark of Tabebuia avellanedae.		2.610
leflunomide
Leflunomide: An isoxazole derivative that inhibits dihydroorotate dehydrogenase, the fourth enzyme in the pyrimidine biosynthetic pathway. It is used an immunosuppressive agent in the treatment of RHEUMATOID ARTHRITIS and PSORIATIC ARTHRITIS.. leflunomide : A monocarboxylic acid amide obtained by formal condensation of the carboxy group of 5-methyl-1,2-oxazole-4-carboxylic acid with the anilino group of 4-(trifluoromethyl)aniline. The prodrug of teriflunomide.		3.620(trifluoromethyl)benzenes;
isoxazoles;
monocarboxylic acid amide		antineoplastic agent;
antiparasitic agent;
EC 1.3.98.1 [dihydroorotate oxidase (fumarate)] inhibitor;
EC 3.1.3.16 (phosphoprotein phosphatase) inhibitor;
hepatotoxic agent;
immunosuppressive agent;
non-steroidal anti-inflammatory drug;
prodrug;
pyrimidine synthesis inhibitor;
tyrosine kinase inhibitor
letrozole
[no description available]		2.0810nitrile;
triazoles		antineoplastic agent;
EC 1.14.14.14 (aromatase) inhibitor
lg 100268
LG 100268: a retinoid X receptor (RXR) selective compound; structure given in first source		2.0810
loperamide
Loperamide: One of the long-acting synthetic ANTIDIARRHEALS; it is not significantly absorbed from the gut, and has no effect on the adrenergic system or central nervous system, but may antagonize histamine and interfere with acetylcholine release locally.. loperamide : A synthetic piperidine derivative, effective against diarrhoea resulting from gastroenteritis or inflammatory bowel disease.		2.610monocarboxylic acid amide;
monochlorobenzenes;
piperidines;
tertiary alcohol		anticoronaviral agent;
antidiarrhoeal drug;
mu-opioid receptor agonist
loratadine
Loratadine: A second-generation histamine H1 receptor antagonist used in the treatment of allergic rhinitis and urticaria. Unlike most classical antihistamines (HISTAMINE H1 ANTAGONISTS) it lacks central nervous system depressing effects such as drowsiness.. loratadine : A benzocycloheptapyridine that is 6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine substituted by a chloro group at position 8 and a 1-(ethoxycarbonyl)piperidin-4-ylidene group at position 11. It is a H1-receptor antagonist commonly employed in the treatment of allergic disorders.		2.610benzocycloheptapyridine;
ethyl ester;
N-acylpiperidine;
organochlorine compound;
tertiary carboxamide		anti-allergic agent;
cholinergic antagonist;
geroprotector;
H1-receptor antagonist
losartan
Losartan: An antagonist of ANGIOTENSIN TYPE 1 RECEPTOR with antihypertensive activity due to the reduced pressor effect of ANGIOTENSIN II.. losartan : A biphenylyltetrazole where a 1,1'-biphenyl group is attached at the 5-position and has an additional trisubstituted imidazol-1-ylmethyl group at the 4'-position		2.610biphenylyltetrazole;
imidazoles		angiotensin receptor antagonist;
anti-arrhythmia drug;
antihypertensive agent;
endothelin receptor antagonist
4-(dimethylamino)-n-(7-(hydroxyamino)-7-oxoheptyl)benzamide
4-(dimethylamino)-N-(7-(hydroxyamino)-7-oxoheptyl)benzamide: structure in first source. 4-(dimethylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]benzamide : A benzamide resulting from the formal condensation of the carboxy group of 4-(dimethylamino)benzoic acid with the amino group of 7-amino-N-hydroxyheptanamide. It is a potent inhibitor of histone deacetylases and induces cell cycle arrest and apoptosis in several human cancer cell lines.		2.610benzamides;
hydroxamic acid;
secondary carboxamide;
tertiary amino compound		antineoplastic agent;
apoptosis inducer;
EC 3.5.1.98 (histone deacetylase) inhibitor
mafenide
Mafenide: A sulfonamide that inhibits the enzyme CARBONIC ANHYDRASE and is used as a topical anti-bacterial agent, especially in burn therapy.		2.610aromatic amine
metformin
Metformin: A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. (From Martindale, The Extra Pharmacopoeia, 30th ed, p289). metformin : A member of the class of guanidines that is biguanide the carrying two methyl substituents at position 1.		2.0810guanidinesenvironmental contaminant;
geroprotector;
hypoglycemic agent;
xenobiotic
methazolamide
Methazolamide: A carbonic anhydrase inhibitor that is used as a diuretic and in the treatment of glaucoma.		2.610sulfonamide;
thiadiazoles
methocarbamol
Methocarbamol: A centrally acting muscle relaxant whose mode of action has not been established. It is used as an adjunct in the symptomatic treatment of musculoskeletal conditions associated with painful muscle spasm. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1206). methocarbamol : A racemate comprising equimolar amounts of (R)- and (S)-methocarbamol. A centrally acting skeletal muscle relaxant, it is used as an adjunct in the short-term symptomatic treatment of painful muscle spasm. The (R)-enantiomer is more active than the (S)-enantiomer.. 2-hydroxy-3-(2-methoxyphenoxy)propyl carbamate : A carbamate ester that is glycerol in which one of the primary alcohol groups has been converted to its 2-methoxyphenyl ether while the other has been converted to the corresponding carbamate ester.		2.610aromatic ether;
carbamate ester;
secondary alcohol
mitoxantrone
Mitoxantrone: An anthracenedione-derived antineoplastic agent.. mitoxantrone : A dihydroxyanthraquinone that is 1,4-dihydroxy-9,10-anthraquinone which is substituted by 6-hydroxy-1,4-diazahexyl groups at positions 5 and 8.		9.2631dihydroxyanthraquinoneanalgesic;
antineoplastic agent
entinostat
[no description available]		2.5820benzamides;
carbamate ester;
primary amino compound;
pyridines;
substituted aniline		antineoplastic agent;
apoptosis inducer;
EC 3.5.1.98 (histone deacetylase) inhibitor
ethylmaleimide
Ethylmaleimide: A sulfhydryl reagent that is widely used in experimental biochemical studies.		2.610maleimidesanticoronaviral agent;
EC 1.3.1.8 [acyl-CoA dehydrogenase (NADP(+))] inhibitor;
EC 2.1.1.122 [(S)-tetrahydroprotoberberine N-methyltransferase] inhibitor;
EC 2.7.1.1 (hexokinase) inhibitor
nabumetone
Nabumetone: A butanone non-steroidal anti-inflammatory drug and cyclooxygenase-2 (COX2) inhibitor that is used in the management of pain associated with OSTEOARTHRITIS and RHEUMATOID ARTHRITIS.. nabumetone : A methyl ketone that is 2-butanone in which one of the methyl hydrogens at position 4 is replaced by a 6-methoxy-2-naphthyl group. A prodrug that is converted to the active metabolite, 6-methoxy-2-naphthylacetic acid, following oral administration. It is shown to have a slightly lower risk of gastrointestinal side effects than most other non-steroidal anti-inflammatory drugs.		2.610methoxynaphthalene;
methyl ketone		cyclooxygenase 2 inhibitor;
non-narcotic analgesic;
non-steroidal anti-inflammatory drug;
prodrug
nafamostat
nafamostat: inhibitor of trypsin, plasmin, pancreatic kallikrein, plasma kallikrein & thrombin; strongly inhibits esterolytic activities of C1r & C1 esterase complement-mediated hemolysis; antineoplastic		2.610benzoic acids;
guanidines
nevirapine
Nevirapine: A potent, non-nucleoside reverse transcriptase inhibitor used in combination with nucleoside analogues for treatment of HIV INFECTIONS and AIDS.. nevirapine : A dipyridodiazepine that is 5,11-dihydro-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepine which is substituted by methyl, oxo, and cyclopropyl groups at positions 4, 6, and 11, respectively. A non-nucleoside reverse transcriptase inhibitor with activity against HIV-1, it is used in combination with other antiretrovirals for the treatment of HIV infection.		2.610cyclopropanes;
dipyridodiazepine		antiviral drug;
HIV-1 reverse transcriptase inhibitor
olprinone
olprinone: RN refers to HCl; structure given in first source		2.0810bipyridines
omeprazole
Omeprazole: A 4-methoxy-3,5-dimethylpyridyl, 5-methoxybenzimidazole derivative of timoprazole that is used in the therapy of STOMACH ULCERS and ZOLLINGER-ELLISON SYNDROME. The drug inhibits an H(+)-K(+)-EXCHANGING ATPASE which is found in GASTRIC PARIETAL CELLS.. omeprazole : A racemate comprising equimolar amounts of (R)- and (S)-omeprazole.. 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole : A member of the class of benzimidazoles that is 1H-benzimidazole which is substituted by a [4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl group at position 2 and a methoxy group at position 5.		2.8630aromatic ether;
benzimidazoles;
pyridines;
sulfoxide
osalmide
osalmide: structure		2.610organic molecular entity
oxethazaine
[no description available]		2.610amino acid amide
palmidrol
palmidrol: a cannabinoid receptor-inactive eCB-related molecule used as prophylactic in helping to prevent respiratory viral infection. palmitoyl ethanolamide : An N-(long-chain-acyl)ethanolamine that is the ethanolamide of palmitic (hexadecanoic) acid.		2.610endocannabinoid;
N-(long-chain-acyl)ethanolamine;
N-(saturated fatty acyl)ethanolamine		anti-inflammatory drug;
anticonvulsant;
antihypertensive agent;
neuroprotective agent
papaverine
Papaverine: An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used in the treatment of impotence and as a vasodilator, especially for cerebral vasodilation. The mechanism of its pharmacological actions is not clear, but it apparently can inhibit phosphodiesterases and it may have direct actions on calcium channels.. papaverine : A benzylisoquinoline alkaloid that is isoquinoline substituted by methoxy groups at positions 6 and 7 and a 3,4-dimethoxybenzyl group at position 1. It has been isolated from Papaver somniferum.		2.610benzylisoquinoline alkaloid;
dimethoxybenzene;
isoquinolines		antispasmodic drug;
vasodilator agent
pentoxifylline
[no description available]		2.610oxopurine
perhexiline
Perhexiline: 2-(2,2-Dicyclohexylethyl)piperidine. Coronary vasodilator used especially for angina of effort. It may cause neuropathy and hepatitis.		2.610piperidinescardiovascular drug
phenazopyridine
Phenazopyridine: A local anesthetic that has been used in urinary tract disorders. Its use is limited by problems with toxicity (primarily blood disorders) and potential carcinogenicity.. phenazopyridine : A diaminopyridine that is 2,6-diaminopyridine substituted at position 3 by a phenylazo group. A local anesthetic that has topical analgesic effect on mucosa lining of the urinary tract. Its use is limited by problems with toxicity (primarily blood disorders) and potential carcinogenicity.		2.610diaminopyridine;
monoazo compound		anticoronaviral agent;
carcinogenic agent;
local anaesthetic;
non-narcotic analgesic
4-phenylbutyric acid
4-phenylbutyric acid: RN refers to the parent cpd. 4-phenylbutyric acid : A monocarboxylic acid the structure of which is that of butyric acid substituted with a phenyl group at C-4. It is a histone deacetylase inhibitor that displays anticancer activity. It inhibits cell proliferation, invasion and migration and induces apoptosis in glioma cells. It also inhibits protein isoprenylation, depletes plasma glutamine, increases production of foetal haemoglobin through transcriptional activation of the gamma-globin gene and affects hPPARgamma activation.		2.610monocarboxylic acidantineoplastic agent;
apoptosis inducer;
EC 3.5.1.98 (histone deacetylase) inhibitor;
prodrug
phenylmethylsulfonyl fluoride
Phenylmethylsulfonyl Fluoride: An enzyme inhibitor that inactivates IRC-50 arvin, subtilisin, and the fatty acid synthetase complex.. phenylmethanesulfonyl fluoride : An acyl fluoride with phenylmethanesulfonyl as the acyl group.		2.610acyl fluorideserine proteinase inhibitor
pimobendan
pimobendan: produces arterial & venous dilatation in dogs; structure given in first source		2.610benzimidazoles;
pyridazinone		cardiotonic drug;
EC 3.1.4.* (phosphoric diester hydrolase) inhibitor;
vasodilator agent
pioglitazone
Pioglitazone: A thiazolidinedione and PPAR GAMMA agonist that is used in the treatment of TYPE 2 DIABETES MELLITUS.. pioglitazone : A member of the class of thiazolidenediones that is 1,3-thiazolidine-2,4-dione substituted by a benzyl group at position 5 which in turn is substituted by a 2-(5-ethylpyridin-2-yl)ethoxy group at position 4 of the phenyl ring. It exhibits hypoglycemic activity.		2.0810aromatic ether;
pyridines;
thiazolidinediones		antidepressant;
cardioprotective agent;
EC 2.7.1.33 (pantothenate kinase) inhibitor;
EC 6.2.1.3 (long-chain-fatty-acid--CoA ligase) inhibitor;
ferroptosis inhibitor;
geroprotector;
hypoglycemic agent;
insulin-sensitizing drug;
PPARgamma agonist;
xenobiotic
pj-34
PJ34 : A member of the class of phenanthridines that is 5,6-dihydrophenanthridine substituted at positions 2 and 6 by (N,N-dimethylglycyl)amino and oxo groups, respectively. It is a potent inhibitor of poly(ADP-ribose) polymerases PARP1 and PARP2 (IC50 of 110 nM and 86 nM, respectively) and exhibits anti-cancer, cardioprotective and neuroprotective properties.		2.610phenanthridines;
secondary carboxamide;
tertiary amino compound		angiogenesis inhibitor;
anti-inflammatory agent;
antiatherosclerotic agent;
antineoplastic agent;
apoptosis inducer;
cardioprotective agent;
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor;
neuroprotective agent
praziquantel
azinox: Russian drug		2.610isoquinolines
probenecid
Probenecid: The prototypical uricosuric agent. It inhibits the renal excretion of organic anions and reduces tubular reabsorption of urate. Probenecid has also been used to treat patients with renal impairment, and, because it reduces the renal tubular excretion of other drugs, has been used as an adjunct to antibacterial therapy.. probenecid : A sulfonamide in which the nitrogen of 4-sulfamoylbenzoic acid is substituted with two propyl groups.		2.610benzoic acids;
sulfonamide		uricosuric drug
probucol
Probucol: A drug used to lower LDL and HDL cholesterol yet has little effect on serum-triglyceride or VLDL cholesterol. (From Martindale, The Extra Pharmacopoeia, 30th ed, p993).. probucol : A dithioketal that is propane-2,2-dithiol in which the hydrogens attached to both sulfur atoms are replaced by 3,5-di-tert-butyl-4-hydroxyphenyl groups. An anticholesteremic drug with antioxidant and anti-inflammatory properties, it is used to treat high levels of cholesterol in blood.		2.610dithioketal;
polyphenol		anti-inflammatory drug;
anticholesteremic drug;
antilipemic drug;
antioxidant;
cardiovascular drug
promazine
Promazine: A phenothiazine with actions similar to CHLORPROMAZINE but with less antipsychotic activity. It is primarily used in short-term treatment of disturbed behavior and as an antiemetic.. promazine : A phenothiazine deriative in which the phenothiazine tricycle has a 3-(dimethylaminopropyl) group at the N-10 position.		2.610phenothiazines;
tertiary amine		antiemetic;
dopaminergic antagonist;
EC 3.4.21.26 (prolyl oligopeptidase) inhibitor;
H1-receptor antagonist;
muscarinic antagonist;
phenothiazine antipsychotic drug;
serotonergic antagonist
promethazine
Promethazine: A phenothiazine derivative with histamine H1-blocking, antimuscarinic, and sedative properties. It is used as an antiallergic, in pruritus, for motion sickness and sedation, and also in animals.. promethazine : A tertiary amine that is a substituted phenothiazine in which the ring nitrogen at position 10 is attached to C-3 of an N,N-dimethylpropan-2-amine moiety.		2.610phenothiazines;
tertiary amine		anti-allergic agent;
anticoronaviral agent;
antiemetic;
antipruritic drug;
H1-receptor antagonist;
local anaesthetic;
sedative
propranolol
Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs.. propranolol : A propanolamine that is propan-2-ol substituted by a propan-2-ylamino group at position 1 and a naphthalen-1-yloxy group at position 3.		2.610naphthalenes;
propanolamine;
secondary amine		anti-arrhythmia drug;
antihypertensive agent;
anxiolytic drug;
beta-adrenergic antagonist;
environmental contaminant;
human blood serum metabolite;
vasodilator agent;
xenobiotic
rabeprazole
Rabeprazole: A 4-(3-methoxypropoxy)-3-methylpyridinyl derivative of timoprazole that is used in the therapy of STOMACH ULCERS and ZOLLINGER-ELLISON SYNDROME. The drug inhibits H(+)-K(+)-EXCHANGING ATPASE which is found in GASTRIC PARIETAL CELLS.		2.1510benzimidazoles;
pyridines;
sulfoxide		anti-ulcer drug;
EC 3.6.3.10 (H(+)/K(+)-exchanging ATPase) inhibitor
3-[(3,5-dibromo-4-hydroxyphenyl)methylidene]-5-iodo-1H-indol-2-one
[no description available]		2.0810indoles
riluzole
Riluzole: A glutamate antagonist (RECEPTORS, GLUTAMATE) used as an anticonvulsant (ANTICONVULSANTS) and to prolong the survival of patients with AMYOTROPHIC LATERAL SCLEROSIS.		2.0810benzothiazoles
rimantadine
Rimantadine: An RNA synthesis inhibitor that is used as an antiviral agent in the prophylaxis and treatment of influenza.		2.610alkylamine
rolipram
[no description available]		2.610pyrrolidin-2-onesantidepressant;
EC 3.1.4.* (phosphoric diester hydrolase) inhibitor
sb 206553
SB 206553: a high-affinity 5-HT(2C/2B) antagonist; structure given in first source		2.0810pyrroloindole
sb 220025
SB 220025: inhibits p38 mitogen-activated protein kinase; structure in first source. SB220025 : Am member of the class of imidazoles carrying piperidin-4-yl, 4-fluophenyl and 2-aminopyrimidin-4-yl substituents at posiitons 1, 4 and 5 respectively.		2.0810aminopyrimidine;
imidazoles;
organofluorine compound;
piperidines		angiogenesis inhibitor;
anti-inflammatory agent;
EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor
sb 202190
4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole: structure given in first source; inhibits p38 MAP kinase		2.0810imidazoles;
organofluorine compound;
phenols;
pyridines		apoptosis inducer;
EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor
scriptaid
scriptide: provokes translocation of GLUT4 to increase glucose uptake; structure in first source		2.610isoquinolines
sebacic acid
sebacic acid : An alpha,omega-dicarboxylic acid that is the 1,8-dicarboxy derivative of octane.		2.610alpha,omega-dicarboxylic acid;
dicarboxylic fatty acid		human metabolite;
plant metabolite
sk&f 86002
6-(4-fluorophenyl)-2,3-dihydro-5-(4-pyridinyl)imidazo(2,1-b)thiazole: inhibits p38 MAP kinase		2.0810imidazoles
fenofibrate
[no description available]		2.610benzochromenone;
delta-lactone;
naphtho-alpha-pyrone		platelet aggregation inhibitor;
Sir2 inhibitor
imatinib
[no description available]		2.5820aromatic amine;
benzamides;
N-methylpiperazine;
pyridines;
pyrimidines		antineoplastic agent;
apoptosis inducer;
tyrosine kinase inhibitor
vorinostat
Vorinostat: A hydroxamic acid and anilide derivative that acts as a HISTONE DEACETYLASE inhibitor. It is used in the treatment of CUTANEOUS T-CELL LYMPHOMA and SEZARY SYNDROME.. vorinostat : A dicarboxylic acid diamide comprising suberic (octanedioic) acid coupled to aniline and hydroxylamine. A histone deacetylase inhibitor, it is marketed under the name Zolinza for the treatment of cutaneous T cell lymphoma (CTCL).		9.2231dicarboxylic acid diamide;
hydroxamic acid		antineoplastic agent;
apoptosis inducer;
EC 3.5.1.98 (histone deacetylase) inhibitor
sulfasalazine
Sulfasalazine: A drug that is used in the management of inflammatory bowel diseases. Its activity is generally considered to lie in its metabolic breakdown product, 5-aminosalicylic acid (see MESALAMINE) released in the colon. (From Martindale, The Extra Pharmacopoeia, 30th ed, p907). sulfasalazine : An azobenzene consisting of diphenyldiazene having a carboxy substituent at the 4-position, a hydroxy substituent at the 3-position and a 2-pyridylaminosulphonyl substituent at the 4'-position.		2.0810
suprofen
Suprofen: An IBUPROFEN-type anti-inflammatory analgesic and antipyretic. It inhibits prostaglandin synthesis and has been proposed as an anti-arthritic.. suprofen : An aromatic ketone that is thiophene substituted at C-2 by a 4-(1-carboxyethyl)benzoyl group.		2.610aromatic ketone;
monocarboxylic acid;
thiophenes		antirheumatic drug;
drug allergen;
EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor;
non-narcotic analgesic;
non-steroidal anti-inflammatory drug;
peripheral nervous system drug
suramin
Suramin: A polyanionic compound with an unknown mechanism of action. It is used parenterally in the treatment of African trypanosomiasis and it has been used clinically with diethylcarbamazine to kill the adult Onchocerca. (From AMA Drug Evaluations Annual, 1992, p1643) It has also been shown to have potent antineoplastic properties.. suramin : A member of the class of phenylureas that is urea in which each of the amino groups has been substituted by a 3-({2-methyl-5-[(4,6,8-trisulfo-1-naphthyl)carbamoyl]phenyl}carbamoyl)phenyl group. An activator of both the rabbit skeletal muscle RyR1 and sheep cardiac RyR2 isoform ryanodine receptor channels, it has been used for the treatment of human African trypanosomiasis for over 100 years.		2.2510naphthalenesulfonic acid;
phenylureas;
secondary carboxamide		angiogenesis inhibitor;
antinematodal drug;
antineoplastic agent;
apoptosis inhibitor;
EC 2.7.11.13 (protein kinase C) inhibitor;
GABA antagonist;
GABA-gated chloride channel antagonist;
purinergic receptor P2 antagonist;
ryanodine receptor agonist;
trypanocidal drug
2-[4-(1,2-diphenylbut-1-enyl)phenoxy]-N,N-dimethylethanamine
[no description available]		2.0810stilbenoid
thalidomide
Thalidomide: A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppressive and anti-angiogenic activity. It inhibits release of TUMOR NECROSIS FACTOR-ALPHA from monocytes, and modulates other cytokine action.. thalidomide : A racemate comprising equimolar amounts of R- and S-thalidomide.. 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione : A dicarboximide that is isoindole-1,3(2H)-dione in which the hydrogen attached to the nitrogen is substituted by a 2,6-dioxopiperidin-3-yl group.		15.163918phthalimides;
piperidones
ticlopidine
Ticlopidine: An effective inhibitor of platelet aggregation commonly used in the placement of STENTS in CORONARY ARTERIES.. ticlopidine : A thienopyridine that is 4,5,6,7-tetrahydrothieno[3,2-c]pyridine in which the hydrogen attached to the nitrogen is replaced by an o-chlorobenzyl group.		2.610monochlorobenzenes;
thienopyridine		anticoagulant;
fibrin modulating drug;
hematologic agent;
P2Y12 receptor antagonist;
platelet aggregation inhibitor
triamterene
Triamterene: A pteridinetriamine compound that inhibits SODIUM reabsorption through SODIUM CHANNELS in renal EPITHELIAL CELLS.. triamterene : Pteridine substituted at positions 2, 4 and 7 with amino groups and at position 6 with a phenyl group. A sodium channel blocker, it is used as a diuretic in the treatment of hypertension and oedema.		2.610pteridinesdiuretic;
sodium channel blocker
trifluoperazine
[no description available]		2.610N-alkylpiperazine;
N-methylpiperazine;
organofluorine compound;
phenothiazines		antiemetic;
calmodulin antagonist;
dopaminergic antagonist;
EC 1.8.1.12 (trypanothione-disulfide reductase) inhibitor;
EC 5.3.3.5 (cholestenol Delta-isomerase) inhibitor;
phenothiazine antipsychotic drug
triflupromazine
Triflupromazine: A phenothiazine used as an antipsychotic agent and as an antiemetic.. triflupromazine : A member of the class of phenothiazines that is 10H-phenothiazine having a trifluoromethyl subsitituent at the 2-position and a 3-(dimethylamino)propyl group at the N-10 position.		2.610organofluorine compound;
phenothiazines;
tertiary amine		anticoronaviral agent;
antiemetic;
dopaminergic antagonist;
first generation antipsychotic
trigonelline
trigonelline: in hydra among other organisms; RN given refers to hydroxide inner salt; structure. N-methylnicotinic acid : A pyridinium ion consisting of nicotinic acid having a methyl substituent on the pyridine nitrogen.. N-methylnicotinate : An iminium betaine that is the conjugate base of N-methylnicotinic acid, arising from deprotonation of the carboxy group.		2.610alkaloid;
iminium betaine		food component;
human urinary metabolite;
plant metabolite
trimethobenzamide
trimethobenzamide: major descriptor (64-84); on-line search BENZAMIDES (64-84); Index Medicus search TRIMETHOBENZAMIDE (64-84); RN given refers to parent cpd. trimethobenzamide : The amide obtained by formal condensation of 3,4,5-trihydroxybenzoic acid with 4-[2-(N,N-dimethylamino)ethoxy]benzylamine. It is used to prevent nausea and vomitting in humans.		2.610benzamides;
tertiary amino compound		antiemetic
trimethoprim
Trimethoprim: A pyrimidine inhibitor of dihydrofolate reductase, it is an antibacterial related to PYRIMETHAMINE. It is potentiated by SULFONAMIDES and the TRIMETHOPRIM, SULFAMETHOXAZOLE DRUG COMBINATION is the form most often used. It is sometimes used alone as an antimalarial. TRIMETHOPRIM RESISTANCE has been reported.. trimethoprim : An aminopyrimidine antibiotic whose structure consists of pyrimidine 2,4-diamine and 1,2,3-trimethoxybenzene moieties linked by a methylene bridge.		2.610aminopyrimidine;
methoxybenzenes		antibacterial drug;
diuretic;
drug allergen;
EC 1.5.1.3 (dihydrofolate reductase) inhibitor;
environmental contaminant;
xenobiotic
troglitazone
Troglitazone: A chroman and thiazolidinedione derivative that acts as a PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS (PPAR) agonist. It was formerly used in the treatment of TYPE 2 DIABETES MELLITUS, but has been withdrawn due to hepatotoxicity.		2.0810chromanes;
thiazolidinone		anticoagulant;
anticonvulsant;
antineoplastic agent;
antioxidant;
EC 6.2.1.3 (long-chain-fatty-acid--CoA ligase) inhibitor;
ferroptosis inhibitor;
hypoglycemic agent;
platelet aggregation inhibitor;
vasodilator agent
tyrphostin a9
[no description available]		2.610alkylbenzenegeroprotector
delavirdine
Delavirdine: A potent, non-nucleoside reverse transcriptase inhibitor with activity specific for HIV-1.. delavirdine : The amide resulting from the formal condensation of 5-[(methylsulfonyl)amino]-1H-indole-2-carboxylic acid and 4-amino group of 1-[3-(isopropylamino)pyridin-2-yl]piperazine, delavirdine is a non-nucleoside reverse transcriptase inhibitor with activity specific for HIV-1. Viral resistance emerges rapidly when delavirdine is used alone, so it is therefore used (as the methanesulfonic acid salt) with other antiretrovirals for combination therapy of HIV infection.		2.610aminopyridine;
indolecarboxamide;
N-acylpiperazine;
sulfonamide		antiviral drug;
HIV-1 reverse transcriptase inhibitor
vesnarinone
[no description available]		2.610organic molecular entity
2,5-dichlorobenzoic acid
2,5-dichlorobenzoic acid : A chlorobenzoic acid that is benzoic acid in which the ring hydrogens at positions 2 and 5 are substituted by chloro groups.		2.5520chlorobenzoic acid;
dichlorobenzene
prednisone
Prednisone: A synthetic anti-inflammatory glucocorticoid derived from CORTISONE. It is biologically inert and converted to PREDNISOLONE in the liver.. prednisone : A synthetic glucocorticoid drug that is particularly effective as an immunosuppressant, and affects virtually all of the immune system. Prednisone is a prodrug that is converted by the liver into prednisolone (a beta-hydroxy group instead of the oxo group at position 11), which is the active drug and also a steroid.		3.782011-oxo steroid;
17alpha-hydroxy steroid;
20-oxo steroid;
21-hydroxy steroid;
3-oxo-Delta(1),Delta(4)-steroid;
C21-steroid;
glucocorticoid;
primary alpha-hydroxy ketone;
tertiary alpha-hydroxy ketone		adrenergic agent;
anti-inflammatory drug;
antineoplastic agent;
immunosuppressive agent;
prodrug
idoxuridine
[no description available]		2.610organoiodine compound;
pyrimidine 2'-deoxyribonucleoside		antiviral drug;
DNA synthesis inhibitor
chloramphenicol
Amphenicol: Chloramphenicol and its derivatives.		2.610C-nitro compound;
carboxamide;
diol;
organochlorine compound		antibacterial drug;
antimicrobial agent;
Escherichia coli metabolite;
geroprotector;
Mycoplasma genitalium metabolite;
protein synthesis inhibitor
glutamine
Glutamine: A non-essential amino acid present abundantly throughout the body and is involved in many metabolic processes. It is synthesized from GLUTAMIC ACID and AMMONIA. It is the principal carrier of NITROGEN in the body and is an important energy source for many cells.. L-glutamine : An optically active form of glutamine having L-configuration.. glutamine : An alpha-amino acid that consists of butyric acid bearing an amino substituent at position 2 and a carbamoyl substituent at position 4.		2.1710amino acid zwitterion;
glutamine family amino acid;
glutamine;
L-alpha-amino acid;
polar amino acid zwitterion;
proteinogenic amino acid		EC 1.14.13.39 (nitric oxide synthase) inhibitor;
Escherichia coli metabolite;
human metabolite;
metabolite;
micronutrient;
mouse metabolite;
nutraceutical;
Saccharomyces cerevisiae metabolite
lysine
Lysine: An essential amino acid. It is often added to animal feed.. lysine : A diamino acid that is caproic (hexanoic) acid bearing two amino substituents at positions 2 and 6.. L-lysine : An L-alpha-amino acid; the L-isomer of lysine.		2.610aspartate family amino acid;
L-alpha-amino acid zwitterion;
L-alpha-amino acid;
lysine;
organic molecular entity;
proteinogenic amino acid		algal metabolite;
anticonvulsant;
Escherichia coli metabolite;
human metabolite;
micronutrient;
mouse metabolite;
nutraceutical;
plant metabolite;
Saccharomyces cerevisiae metabolite
carbostyril
Quinolones: A group of derivatives of naphthyridine carboxylic acid, quinoline carboxylic acid, or NALIDIXIC ACID.. quinolin-2(1H)-one : A quinolone that is 1,2-dihydroquinoline substituted by an oxo group at position 2.		3.2110monohydroxyquinoline;
quinolone		bacterial xenobiotic metabolite
phenylethyl alcohol
Phenylethyl Alcohol: An antimicrobial, antiseptic, and disinfectant that is used also as an aromatic essence and preservative in pharmaceutics and perfumery.. 2-phenylethanol : A primary alcohol that is ethanol substituted by a phenyl group at position 2.		2.610benzenes;
primary alcohol		Aspergillus metabolite;
fragrance;
plant growth retardant;
plant metabolite;
Saccharomyces cerevisiae metabolite
zoxazolamine
Zoxazolamine: A uricosuric and muscle relaxant. Zoxazolamine acts centrally as a muscle relaxant, but the mechanism of its action is not understood.		2.610benzoxazole
4-nitrobenzoic acid
4-nitrobenzoic acid: RN given refers to parent cpd. 4-nitrobenzoic acid : A nitrobenzoic acid having the nitro group at the 4-position.		2.2510nitrobenzoic acid
cycloheximide
Cycloheximide: Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.. cycloheximide : A dicarboximide that is 4-(2-hydroxyethyl)piperidine-2,6-dione in which one of the hydrogens attached to the carbon bearing the hydroxy group is replaced by a 3,5-dimethyl-2-oxocyclohexyl group. It is an antibiotic produced by the bacterium Streptomyces griseus.		2.610antibiotic fungicide;
cyclic ketone;
dicarboximide;
piperidine antibiotic;
piperidones;
secondary alcohol		anticoronaviral agent;
bacterial metabolite;
ferroptosis inhibitor;
neuroprotective agent;
protein synthesis inhibitor
ficusin
Ficusin: A naturally occurring furocoumarin, found in PSORALEA. After photoactivation with UV radiation, it binds DNA via single and double-stranded cross-linking.. psoralen : The simplest member of the class of psoralens that is 7H-furo[3,2-g]chromene having a keto group at position 7. It has been found in plants like Psoralea corylifolia and Ficus salicifolia.		2.610psoralensplant metabolite
tubercidin
Tubercidin: An antibiotic purine ribonucleoside that readily substitutes for adenosine in the biological system, but its incorporation into DNA and RNA has an inhibitory effect on the metabolism of these nucleic acids.. tubercidin : An N-glycosylpyrrolopyrimidine that is adenosine in which the in the 5-membered ring that is not attached to the ribose moiety is replaced by a carbon. Tubercidin is produced in the culture broth of Streptomyces tubericidus.		2.610antibiotic antifungal agent;
N-glycosylpyrrolopyrimidine;
ribonucleoside		antimetabolite;
antineoplastic agent;
bacterial metabolite
cytarabine
[no description available]		8.5911beta-D-arabinoside;
monosaccharide derivative;
pyrimidine nucleoside		antimetabolite;
antineoplastic agent;
antiviral agent;
immunosuppressive agent
trifluridine
Trifluridine: An antiviral derivative of THYMIDINE used mainly in the treatment of primary keratoconjunctivitis and recurrent epithelial keratitis due to HERPES SIMPLEX virus. (From Martindale, The Extra Pharmacopoeia, 30th ed, p557). trifluridine : A pyrimidine 2'-deoxyribonucleoside compound having 5-trifluoromethyluracil as the nucleobase. An antiviral drug used mainly in the treatment of primary keratoconjunctivitis and recurrent epithelial keratitis.		2.610nucleoside analogue;
organofluorine compound;
pyrimidine 2'-deoxyribonucleoside		antimetabolite;
antineoplastic agent;
antiviral drug;
EC 2.1.1.45 (thymidylate synthase) inhibitor
threonine
Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins.. threonine : An alpha-amino acid in which one of the hydrogens attached to the alpha-carbon of glycine is substituted by a 1-hydroxyethyl group.		4.4860amino acid zwitterion;
aspartate family amino acid;
L-alpha-amino acid;
proteinogenic amino acid;
threonine		algal metabolite;
Escherichia coli metabolite;
human metabolite;
micronutrient;
mouse metabolite;
nutraceutical;
plant metabolite;
Saccharomyces cerevisiae metabolite
4-chlorobenzoic acid
4-chlorobenzoic acid: RN given refers to parent cpd. 4-chlorobenzoic acid : A monochlorobenzoic acid carrying a chloro substituent at position 4.		2.2510monochlorobenzoic acidbacterial xenobiotic metabolite
9,10-anthraquinone
9,10-anthraquinone : An anthraquinone that is anthracene in which positions 9 and 10 have been oxidised to carbonyls.		2.610anthraquinone
salicylanilide
salicylanilide: RN given refers to parent cpd. salicylanilide : An amide of salicylic acid and of aniline; it is therefore both a salicylamide and an anilide.		2.610benzanilide fungicide;
salicylamides;
salicylanilides
gramine
gramine : An aminoalkylindole that is indole carrying a dimethylaminomethyl substituent at postion 3.		2.610aminoalkylindole;
indole alkaloid;
tertiary amino compound		antibacterial agent;
antiviral agent;
plant metabolite;
serotonergic antagonist
aminacrine
Aminacrine: A highly fluorescent anti-infective dye used clinically as a topical antiseptic and experimentally as a mutagen, due to its interaction with DNA. It is also used as an intracellular pH indicator.. 9-aminoacridine : An aminoacridine that is acridine in which the hydrogen at position 9 is replaced by an amino group. A fluorescent dyd and topical antiseptic agent, it is used (usually as the hydrochloride salt) in eye drops for the treatment of superficial eye infections.		2.610aminoacridines;
primary amino compound		acid-base indicator;
antiinfective agent;
antiseptic drug;
fluorescent dye;
MALDI matrix material;
mutagen
quinaldic acid
[no description available]		2.2510quinolinemonocarboxylic acidhuman metabolite;
Saccharomyces cerevisiae metabolite
4-tert-butylbenzoic acid
4-tert-butylbenzoic acid: RN given refers to parent cpd		2.2510alkylbenzene
3-toluic acid
3-toluic acid: RN given refers to parent cpd; structure		2.2510methylbenzoic acidhuman xenobiotic metabolite
methyl gallate
methyl gallate: has both immunosuppressive and phytogenic antineoplastic activities; isolated from Acer saccharinum. methyl 3,4,5-trihydroxybenzoate : A gallate ester obtained by the formal condensation of gallic acid with methanol. It exhibits anti-oxidant, anti-tumor, anti-microbial and anti-inflammatory properties.		2.610gallate esteranti-inflammatory agent;
antioxidant;
plant metabolite
3,5-dinitrobenzoic acid
3,5-dinitrobenzoic acid : A member of the class of benzoic acids that is benzoic acid in which the hydrogens at positions 3 and 5 are replaced by nitro groups.		2.2510benzoic acids;
C-nitro compound
4-anisic acid
4-methoxybenzoic acid: structure in first source. 4-methoxybenzoic acid : A methoxybenzoic acid substituted with a methoxy group at position C-4.		2.2510methoxybenzoic acidplant metabolite
monobenzone
monobenzone: structure. monobenzone : The monobenzyl ether of hydroquinone. It is used as a topical drug for medical depigmentation.		2.610benzyl etherallergen;
dermatologic drug;
melanin synthesis inhibitor
pyrroles
1H-pyrrole : A tautomer of pyrrole that has the double bonds at positions 2 and 4.. pyrrole : A five-membered monocyclic heteroarene comprising one NH and four CH units which forms the parent compound of the pyrrole group of compounds. Its five-membered ring structure has three tautomers. A 'closed class'.. azole : Any monocyclic heteroarene consisting of a five-membered ring containing nitrogen. Azoles can also contain one or more other non-carbon atoms, such as nitrogen, sulfur or oxygen.		5.3360pyrrole;
secondary amine
2-chlorobenzoic acid
2-chlorobenzoic acid: RN given refers to parent cpd. chlorobenzoic acid : Any member of the class of benzoic acids in which the benzene ring is substituted by at least one chloro group.. 2-chlorobenzoic acid : A monochlorobenzoic acid having the chloro group at the 2-position.		2.25102-halobenzoic acid;
monochlorobenzoic acid		plant hormone;
plant metabolite
ditiocarb
Ditiocarb: A chelating agent that has been used to mobilize toxic metals from the tissues of humans and experimental animals. It is the main metabolite of DISULFIRAM.. diethyldithiocarbamic acid : A member of the class of dithiocarbamic acids that is diethylcarbamic acid in which both of the oxygens are replaced by sulfur.		2.610dithiocarbamic acidschelator;
copper chelator
catechin
Catechin: An antioxidant flavonoid, occurring especially in woody plants as both (+)-catechin and (-)-epicatechin (cis) forms.. catechin : Members of the class of hydroxyflavan that have a flavan-3-ol skeleton and its substituted derivatives.. rac-catechin : A racemate comprising equimolar amounts of (+)- and (-)-catechin. (+)-catechin : The (+)-enantiomer of catechin and a polyphenolic antioxidant plant metabolite.		2.610catechinantioxidant;
plant metabolite
quinazolines
Quinazolines: A group of aromatic heterocyclic compounds that contain a bicyclic structure with two fused six-membered aromatic rings, a benzene ring and a pyrimidine ring.. quinazoline : A mancude organic heterobicyclic parent that is naphthalene in which the carbon atoms at positions 1 and 3 have been replaced by nitrogen atoms.. quinazolines : Any organic heterobicyclic compound based on a quinazoline skeleton and its substituted derivatives.		2.3110azaarene;
mancude organic heterobicyclic parent;
ortho-fused heteroarene;
quinazolines
indazoles
Indazoles: A group of heterocyclic aromatic organic compounds consisting of the fusion of BENZENE and PYRAZOLES.		3.6411indazole
isoxazoles
Isoxazoles: Azoles with an OXYGEN and a NITROGEN next to each other at the 1,2 positions, in contrast to OXAZOLES that have nitrogens at the 1,3 positions.. isoxazole : A monocyclic heteroarene with a structure consisting of a 5-membered ring containing three carbon atoms and an oxygen and nitrogen atom adjacent to each other. It is the parent of the class of isoxazoles.. isoxazoles : Oxazoles in which the N and O atoms are adjacent.		3.2110isoxazoles;
mancude organic heteromonocyclic parent;
monocyclic heteroarene
thiazoles
[no description available]		2.21101,3-thiazoles;
mancude organic heteromonocyclic parent;
monocyclic heteroarene
pyrazines
Pyrazines: A heterocyclic aromatic organic compound with the chemical formula C4H4N2.. pyrazine : A diazine that is benzene in which the carbon atoms at positions 1 and 4 have been replaced by nitrogen atoms.		6.5590diazine;
pyrazines		Daphnia magna metabolite
hydrazine
diamine : Any polyamine that contains two amino groups.		5.0821azane;
hydrazines		EC 4.3.1.10 (serine-sulfate ammonia-lyase) inhibitor
azacitidine
Azacitidine: A pyrimidine analogue that inhibits DNA methyltransferase, impairing DNA methylation. It is also an antimetabolite of cytidine, incorporated primarily into RNA. Azacytidine has been used as an antineoplastic agent.. 5-azacytidine : An N-glycosyl-1,3,5-triazine that is 4-amino-1,3,5-triazin-2(1H)-one substituted by a beta-D-ribofuranosyl residue via an N-glycosidic linkage. An antineoplastic agent, it is used in the treatment of myeloid leukaemia.		2.8730N-glycosyl-1,3,5-triazine;
nucleoside analogue		antineoplastic agent
4-fluorobenzoic acid
[no description available]		2.2510fluorobenzoic acidbacterial xenobiotic metabolite
lucanthone
Lucanthone: One of the SCHISTOSOMICIDES, it has been replaced largely by HYCANTHONE and more recently PRAZIQUANTEL. (From Martindale The Extrapharmacopoeia, 30th ed., p46). lucanthone : A thioxanthen-9-one compound having a methyl substituent at the 1-position and a 2-[(diethylamino)ethyl]amino substituent at the 4-position. Formerly used for the treatment of schistosomiasis. It is a prodrug, being metabolised to hycanthone.		2.610thioxanthenesadjuvant;
antineoplastic agent;
EC 5.99.1.2 (DNA topoisomerase) inhibitor;
EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor;
mutagen;
photosensitizing agent;
prodrug;
schistosomicide drug
cepharanthine
cepharanthine: isoquinoline alkaloid from tubers of STEPHANIA; stimulates recovery of immunologic function in lymphatic system after administration of antineoplastic agents or x-irradiation. cepharanthine : A bisbenzylisoquinoline alkaloid from tubers of Stephania; stimulates recovery of immunologic function in lymphatic system after administration of antineoplastic agents or x-irradiation.		2.610bisbenzylisoquinoline alkaloid;
isoquinolines
aloe emodin
aloe emodin: structure distinct from emodin; this does not mean emodin from aloe. Aloe emodin : A dihydroxyanthraquinone that is chrysazin carrying a hydroxymethyl group at position 3. It has been isolated from plant species of the genus Aloe.		2.610aromatic primary alcohol;
dihydroxyanthraquinone		antineoplastic agent;
plant metabolite
chrysophanic acid
chrysophanic acid: RN given refers to parent cpd; structure in Merck, 9th ed, #2260. chrysophanol : A trihydroxyanthraquinone that is chrysazin with a methyl substituent at C-3. It has been isolated from Aloe vera and exhibits antiviral and anti-inflammatory activity.		2.610dihydroxyanthraquinoneanti-inflammatory agent;
antiviral agent;
plant metabolite
emetine
Emetine: The principal alkaloid of ipecac, from the ground roots of Uragoga (or Cephaelis) ipecacuanha or U. acuminata, of the Rubiaceae. It is used as an amebicide in many different preparations and may cause serious cardiac, hepatic, or renal damage and violent diarrhea and vomiting. Emetine inhibits protein synthesis in EUKARYOTIC CELLS but not PROKARYOTIC CELLS.. emetine : A pyridoisoquinoline comprising emetam having methoxy substituents at the 6'-, 7'-, 10- and 11-positions. It is an antiprotozoal agent and emetic. It inhibits SARS-CoV2, Zika and Ebola virus replication and displays antimalarial, antineoplastic and antiamoebic properties.		2.610isoquinoline alkaloid;
pyridoisoquinoline		antiamoebic agent;
anticoronaviral agent;
antiinfective agent;
antimalarial;
antineoplastic agent;
antiprotozoal drug;
antiviral agent;
autophagy inhibitor;
emetic;
expectorant;
plant metabolite;
protein synthesis inhibitor
osthol
osthol: from Cnidium monnieri and Angelica pubescens (both Apiaceae); structure given in first source		2.610botanical anti-fungal agent;
coumarins		metabolite
flavanone
flavanone: RN given refers to cpd with unspecified isomeric designation; structure in first source. flavanone : The simplest member of the class of flavanones that consists of flavan bearing an oxo substituent at position 4.		2.610flavanones
phloretic acid
phloretic acid: structure. N-hydroxysuccinimide ester : An ester of N-hydroxysuccinimide.. phloretic acid : A hydroxy monocarboxylic acid consisting of propionic acid having a 4-hydroxyphenyl group at the 3-position.		2.610hydroxy monocarboxylic acidplant metabolite
oleanolic acid
[no description available]		2.610hydroxy monocarboxylic acid;
pentacyclic triterpenoid		plant metabolite
podophyllotoxin
Podophyllum: A genus of poisonous American herbs, family BERBERIDACEAE. The roots yield PODOPHYLLOTOXIN and other pharmacologically important agents. The plant was formerly used as a cholagogue and cathartic. It is different from the European mandrake, MANDRAGORA.		2.0810furonaphthodioxole;
lignan;
organic heterotetracyclic compound		antimitotic;
antineoplastic agent;
keratolytic drug;
microtubule-destabilising agent;
plant metabolite;
tubulin modulator
angelicin
angelicin: used as tranquillizer; sedative; or anticonvulsant; structure		2.610furanocoumarin
cumic acid
cumic acid : A member of the class of benzoic acids that is cumene substituted by at least one carboxy group.. p-cumic acid : A cumic acid that consists of benzoic acid substituted by an isopropyl group at position 4.		2.2510cumic acidplant metabolite
diperodon
diperodon: RN given refers to parent cpd; structure given in first source		2.610carbamate ester
formestane
[no description available]		2.081017-oxo steroid;
3-oxo-Delta(4) steroid;
enol;
hydroxy steroid		antineoplastic agent;
EC 1.14.14.14 (aromatase) inhibitor
4-acetylbenzoic acid
4-acetylbenzoic acid: structure in first source		2.2510
3-bromopropionic acid
[no description available]		2.2510
megestrol acetate
[no description available]		2.61020-oxo steroid;
3-oxo-Delta(4) steroid;
acetate ester;
steroid ester		antineoplastic agent;
appetite enhancer;
contraceptive drug;
progestin;
synthetic oral contraceptive
acetylcysteine
N-acetyl-L-cysteine : An N-acetyl-L-amino acid that is the N-acetylated derivative of the natural amino acid L-cysteine.		2.610acetylcysteine;
L-cysteine derivative;
N-acetyl-L-amino acid		antidote to paracetamol poisoning;
antiinfective agent;
antioxidant;
antiviral drug;
ferroptosis inhibitor;
geroprotector;
human metabolite;
mucolytic;
radical scavenger;
vulnerary
hydroxychloroquine sulfate
[no description available]		2.5820
ethambutol
Ethambutol: An antitubercular agent that inhibits the transfer of mycolic acids into the cell wall of the tubercle bacillus. It may also inhibit the synthesis of spermidine in mycobacteria. The action is usually bactericidal, and the drug can penetrate human cell membranes to exert its lethal effect. (From Smith and Reynard, Textbook of Pharmacology, 1992, p863). ethambutol : An ethylenediamine derivative that is ethane-1,2-diamine in which one hydrogen attached to each of the nitrogens is sutstituted by a 1-hydroxybutan-2-yl group (S,S-configuration). It is a bacteriostatic antimycobacterial drug, effective against Mycobacterium tuberculosis and some other mycobacteria. It is used (as the dihydrochloride salt) in combination with other antituberculous drugs in the treatment of pulmonary and extrapulmonary tuberculosis; resistant strains of M. tuberculosis are readily produced if ethambutol is used alone.		2.610ethanolamines;
ethylenediamine derivative		antitubercular agent;
environmental contaminant;
xenobiotic
metformin hydrochloride
metformin hydrochloride : A hydrochloride resulting from the reaction of metformin with one molar equivalent of hydrogen chloride.		2.610hydrochlorideenvironmental contaminant;
hypoglycemic agent;
xenobiotic
antimycin a
[no description available]		2.610benzamides;
formamides;
macrodiolide;
phenols		antifungal agent;
mitochondrial respiratory-chain inhibitor;
piscicide
vancomycin
Vancomycin: Antibacterial obtained from Streptomyces orientalis. It is a glycopeptide related to RISTOCETIN that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear.. vancomycin : A complex glycopeptide from Streptomyces orientalis. It inhibits a specific step in the synthesis of the peptidoglycan layer in the Gram-positive bacteria Staphylococcus aureus and Clostridium difficile.		2.2510glycopeptideantibacterial drug;
antimicrobial agent;
bacterial metabolite
5,5'-dimethyl-2,2'-bipyridyl
5,5'-dimethyl-2,2'-bipyridyl: structure in first source		2.610bipyridines
dichlorobenzyl alcohol
2,4-dichlorobenzyl alcohol : A member of the class of benzyl alcohols that is benzyl alcohol in which the hydrogens at positions 2 and 4 are replaced by chlorines.		2.610benzyl alcohols;
dichlorobenzene		antiseptic drug
amiloride hydrochloride, anhydrous
amiloride hydrochloride : A hydrochloride obtained by combining amiloride with one molar equivalent of hydrochloric acid.		2.0810hydrochloridediuretic;
sodium channel blocker
acadesine
[no description available]		2.08101-ribosylimidazolecarboxamide;
aminoimidazole;
nucleoside analogue		antineoplastic agent;
platelet aggregation inhibitor
stavudine
Stavudine: A dideoxynucleoside analog that inhibits reverse transcriptase and has in vitro activity against HIV.. stavudine : A nucleoside analogue obtained by formal dehydration across positions 2 and 3 of thymidine. An inhibitor of HIV-1 reverse transcriptase		2.610dihydrofuran;
nucleoside analogue;
organic molecular entity		antimetabolite;
antiviral agent;
EC 2.7.7.49 (RNA-directed DNA polymerase) inhibitor
nitroxoline
nitroxoline: structure in Merck Index, 9th ed, #6475; RN given refers to parent cpd. nitroxoline : A monohydroxyquinoline in which the hydroxy group is positioned at C-8 with a nitro group trans to it at C-5.		3.5110C-nitro compound;
monohydroxyquinoline		antifungal agent;
antiinfective agent;
antimicrobial agent;
renal agent
dideoxyadenosine
Dideoxyadenosine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is an inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase. Its principal side effect is nephrotoxicity. In vivo, dideoxyadenosine is rapidly metabolized to DIDANOSINE (ddI) by enzymatic deamination; ddI is then converted to dideoxyinosine monophosphate and ultimately to dideoxyadenosine triphosphate, the putative active metabolite.		2.610adenosines;
purine 2',3'-dideoxyribonucleoside		EC 3.5.4.4 (adenosine deaminase) inhibitor;
EC 4.6.1.1 (adenylate cyclase) inhibitor
clonidine hydrochloride
[no description available]		2.1510dichlorobenzene
cladribine
[no description available]		2.0810organochlorine compound;
purine 2'-deoxyribonucleoside		antineoplastic agent;
immunosuppressive agent
vidarabine
adenine arabinoside : A purine nucleoside in which adenine is attached to arabinofuranose via a beta-N(9)-glycosidic bond.		2.5920beta-D-arabinoside;
purine nucleoside		antineoplastic agent;
bacterial metabolite;
nucleoside antibiotic
3-deazaadenosine
3-deazaadenosine: RN given refers to parent cpd.		2.610
zalcitabine
Zalcitabine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication at low concentrations, acting as a chain-terminator of viral DNA by binding to reverse transcriptase. Its principal toxic side effect is axonal degeneration resulting in peripheral neuropathy.. zalcitabine : A pyrimidine 2',3'-dideoxyribonucleoside compound having cytosine as the nucleobase.		2.610pyrimidine 2',3'-dideoxyribonucleosideantimetabolite;
antiviral drug;
HIV-1 reverse transcriptase inhibitor
ancitabine
Ancitabine: Congener of CYTARABINE that is metabolized to cytarabine and thereby maintains a more constant antineoplastic action.. ancitabine : An organic heterotricyclic compound resulting from the formal condensation of the oxo group of cytidine to the 2' position with loss of water to give the corresponding cyclic ether. A prodrug, it is metabolised to the antineoplastic agent cytarabine, so is used to maintain a more constant antineoplastic action.		2.610diol;
organic heterotricyclic compound		antimetabolite;
antineoplastic agent;
prodrug
chloropyramine
chloropyramine: RN given refers to parent cpd; structure		2.610aminopyridine
levamisole
Levamisole: An antihelminthic drug that has been tried experimentally in rheumatic disorders where it apparently restores the immune response by increasing macrophage chemotaxis and T-lymphocyte function. Paradoxically, this immune enhancement appears to be beneficial in rheumatoid arthritis where dermatitis, leukopenia, and thrombocytopenia, and nausea and vomiting have been reported as side effects. (From Smith and Reynard, Textbook of Pharmacology, 1991, p435-6). levamisole : A 6-phenyl-2,3,5,6-tetrahydroimidazo[2,1-b][1,3]thiazole that has S configuration. It is used (generally as the monohydrochloride salt) to treat parasitic worm infections in pigs, sheep and cattle and was formerly used in humans as an adjuvant to chemotherapy for the treatment of various cancers. It is also widely used as an adulterant to coccaine.		2.6106-phenyl-2,3,5,6-tetrahydroimidazo[2,1-b][1,3]thiazoleantinematodal drug;
antirheumatic drug;
EC 3.1.3.1 (alkaline phosphatase) inhibitor;
immunological adjuvant;
immunomodulator
n'-nitrosonornicotine
N'-nitrosonornicotine: structure; a potent carcinogen in laboratory animals		2.610pyridines;
pyrrolidines
daunorubicin
Daunorubicin: A very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of LEUKEMIA and other NEOPLASMS.. anthracycline : Anthracyclines are polyketides that have a tetrahydronaphthacenedione ring structure attached by a glycosidic linkage to the amino sugar daunosamine.. daunorubicin : A natural product found in Actinomadura roseola.		2.610aminoglycoside antibiotic;
anthracycline;
p-quinones;
tetracenequinones		antineoplastic agent;
bacterial metabolite
zidovudine
Zidovudine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia.. zidovudine : A pyrimidine 2',3'-dideoxyribonucleoside compound having a 3'-azido substituent and thymine as the nucleobase.		2.5820azide;
pyrimidine 2',3'-dideoxyribonucleoside		antimetabolite;
antiviral drug;
HIV-1 reverse transcriptase inhibitor
buspirone hydrochloride
buspirone hydrochloride : A hydrochloride salt resulting from the reaction of equimolar amounts of buspirone and hydrogen chloride.		2.1510hydrochlorideanxiolytic drug;
EC 3.4.21.26 (prolyl oligopeptidase) inhibitor;
sedative;
serotonergic agonist
etoposide
[no description available]		8.5911beta-D-glucoside;
furonaphthodioxole;
organic heterotetracyclic compound		antineoplastic agent;
DNA synthesis inhibitor
ribavirin
Rebetron: Rebetron is tradename		2.6101-ribosyltriazole;
aromatic amide;
monocarboxylic acid amide;
primary carboxamide		anticoronaviral agent;
antiinfective agent;
antimetabolite;
antiviral agent;
EC 2.7.7.49 (RNA-directed DNA polymerase) inhibitor
pyridoxal phosphate
[no description available]		2.610pyridinecarbaldehyde
lonidamine
lonidamine: structure. lonidamine : A member of the class of indazoles that is 1H-indazole that is substituted at positions 1 and 3 by 2,4-dichlorobenzyl and carboxy groups, respectively.		2.0810dichlorobenzene;
indazoles;
monocarboxylic acid		antineoplastic agent;
antispermatogenic agent;
EC 2.7.1.1 (hexokinase) inhibitor;
geroprotector
nitazoxanide
nitazoxanide: a 5-nitrothiazolyl derivative used for a broad range of intestinal parasitic infections including CRYPTOSPORIDIUM and GIARDIA; it is a redox-active nitrothiazolyl-salicylamide prodrug		2.610benzamides;
carboxylic ester
captopril
Captopril: A potent and specific inhibitor of PEPTIDYL-DIPEPTIDASE A. It blocks the conversion of ANGIOTENSIN I to ANGIOTENSIN II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the RENIN-ANGIOTENSIN SYSTEM and inhibits pressure responses to exogenous angiotensin.. captopril : A L-proline derivative in which L-proline is substituted on nitrogen with a (2S)-2-methyl-3-sulfanylpropanoyl group. It is used as an anti-hypertensive ACE inhibitor drug.		2.610alkanethiol;
L-proline derivative;
N-acylpyrrolidine;
pyrrolidinemonocarboxylic acid		antihypertensive agent;
EC 3.4.15.1 (peptidyl-dipeptidase A) inhibitor
oltipraz
oltipraz : A 1,2-dithiole that is 3H-1,2-dithiole-3-thione substituted at positions 4 and 5 by methyl and pyrazin-2-yl groups respectively.		2.6101,2-dithiole;
pyrazines		angiogenesis modulating agent;
antimutagen;
antineoplastic agent;
antioxidant;
EC 3.1.3.48 (protein-tyrosine-phosphatase) inhibitor;
neurotoxin;
protective agent;
schistosomicide drug
fiacitabine
fiacitabine: anti-herpes virus agent which also inhibits growth of certain human tumor cell lines in vitro.		2.610
simvastatin
Simvastatin: A derivative of LOVASTATIN and potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL RECEPTORS, it increases breakdown of LDL CHOLESTEROL.. simvastatin : A member of the class of hexahydronaphthalenes that is lovastatin in which the 2-methylbutyrate ester moiety has been replaced by a 2,2-dimethylbutyrate ester group. It is used as a cholesterol-lowering and anti-cardiovascular disease drug.		2.0810delta-lactone;
fatty acid ester;
hexahydronaphthalenes;
statin (semi-synthetic)		EC 1.1.1.34/EC 1.1.1.88 (hydroxymethylglutaryl-CoA reductase) inhibitor;
EC 3.4.24.83 (anthrax lethal factor endopeptidase) inhibitor;
ferroptosis inducer;
geroprotector;
prodrug
atomoxetine hydrochloride
Atomoxetine Hydrochloride: A propylamine derivative and selective ADRENERGIC UPTAKE INHIBITOR that is used in the treatment of ATTENTION DEFICIT HYPERACTIVITY DISORDER.. atomoxetine hydrochloride : The hydrochloride salt of atomoxetine.		2.1510hydrochlorideadrenergic uptake inhibitor;
antidepressant
itraconazole
Itraconazole: A triazole antifungal agent that inhibits cytochrome P-450-dependent enzymes required for ERGOSTEROL synthesis.. itraconazole : An N-arylpiperazine that is cis-ketoconazole in which the imidazol-1-yl group is replaced by a 1,2,4-triazol-1-yl group and in which the actyl group attached to the piperazine moiety is replaced by a p-[(+-)1-sec-butyl-5-oxo-1,5-dihydro-4H-1,2,4-triazol-4-yl]phenyl group. A potent P-glycoprotein and CYP3A4 inhibitor, it is used as an antifungal drug for the treatment of various fungal infections, including aspergillosis, blastomycosis, candidiasis, chromoblastomycosis, coccidioidomycosis, cryptococcosis, histoplasmosis, and sporotrichosis.		2.0810aromatic ether;
conazole antifungal drug;
cyclic ketal;
dichlorobenzene;
dioxolane;
N-arylpiperazine;
triazole antifungal drug;
triazoles		EC 3.6.3.44 (xenobiotic-transporting ATPase) inhibitor;
Hedgehog signaling pathway inhibitor;
P450 inhibitor
pravadoline
[no description available]		2.0810
ranolazine
Ranolazine: An acetanilide and piperazine derivative that functions as a SODIUM CHANNEL BLOCKER and prevents the release of enzymes during MYOCARDIAL ISCHEMIA. It is used in the treatment of ANGINA PECTORIS.. N-(2,6-dimethylphenyl)-2-{4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]piperazin-1-yl}acetamide : An aromatic amide obtained by formal condensation of the carboxy group of 2-{4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]piperazin-1-yl}acetic acid with the amino group of 2,6-dimethylaniline.. ranolazine : A racemate comprising equal amounts of (R)- and (S)-ranolazine. Used for treatment of chronic angina.		2.610aromatic amide;
monocarboxylic acid amide;
monomethoxybenzene;
N-alkylpiperazine;
secondary alcohol
brequinar
brequinar : A quinolinemonocarboxylic acid that is quinoline substituted by 2'-fluoro[1,1'-biphenyl]-4-yl, methyl, carboxy and fluoro groups at positions 2, 3, 4, and 6, respectively. It is an inhibitor of dihydroorotate dehydrogenase, an enzyme that is required for de novo pyrimidine biosynthesis. The compound exhibits antineoplastic and antiviral properties.		2.610biphenyls;
monocarboxylic acid;
monofluorobenzenes;
quinolinemonocarboxylic acid		anticoronaviral agent;
antimetabolite;
antineoplastic agent;
antiviral agent;
EC 1.3.5.2 [dihydroorotate dehydrogenase (quinone)] inhibitor;
immunosuppressive agent;
pyrimidine synthesis inhibitor
imiquimod
Imiquimod: A topically-applied aminoquinoline immune modulator that induces interferon production. It is used in the treatment of external genital and perianal warts, superficial CARCINOMA, BASAL CELL; and ACTINIC KERATOSIS.. imiquimod : An imidazoquinoline fused [4,5-c] carrying isobutyl and amino substituents at N-1 and C-4 respectively. A prescription medication, it acts as an immune response modifier and is used to treat genital warts, superficial basal cell carcinoma, and actinic keratosis.		2.610imidazoquinolineantineoplastic agent;
interferon inducer
adefovir
adefovir: inhibitor of African swine fever virus. adefovir(1-) : A organophosphonate oxoanion obtained by removal of a proton from the phosphonate group of adefovir, a nucleoside reverse transcriptase inhibitor. It is the major microspecies at pH 7.3 (according to Marvin v 6.2.0.).. adefovir : A member of the class of phosphonic acids that is methylphosphonic acid in which one of the methyl hydrogens has been replaced by a 2-(6-amino-9H-purin-9-yl)ethoxy group. An inhibitor of HIV-1 reverse transcriptase, the bis(t-butoxycarbonyloxymethyl) ester (dipivoxil ester) prodrug is used to treat chronic hepatitis B viral infection.		2.6106-aminopurines;
ether;
phosphonic acids		antiviral drug;
DNA synthesis inhibitor;
drug metabolite;
HIV-1 reverse transcriptase inhibitor;
nephrotoxic agent
zileuton
[no description available]		2.08101-benzothiophenes;
ureas		anti-asthmatic drug;
EC 1.13.11.34 (arachidonate 5-lipoxygenase) inhibitor;
ferroptosis inhibitor;
leukotriene antagonist;
non-steroidal anti-inflammatory drug
niguldipine
[no description available]		2.0810diarylmethane
cidofovir anhydrous
Cidofovir: An acyclic nucleoside phosphonate that acts as a competitive inhibitor of viral DNA polymerases. It is used in the treatment of RETINITIS caused by CYTOMEGALOVIRUS INFECTIONS and may also be useful for treating HERPESVIRUS INFECTIONS.. cidofovir anhydrous : Cytosine substituted at the 1 position by a 3-hydroxy-2-(phosphonomethoxy)propyl group (S configuration). A nucleoside analogue, it is an injectable antiviral used for the treatment of cytomegalovirus (CMV) retinitis in AIDS patients.		2.610phosphonic acids;
pyrimidone		anti-HIV agent;
antineoplastic agent;
antiviral drug;
photosensitizing agent
topotecan
Topotecan: An antineoplastic agent used to treat ovarian cancer. It works by inhibiting DNA TOPOISOMERASES, TYPE I.. topotecan : A pyranoindolizinoquinoline used as an antineoplastic agent. It is a derivative of camptothecin and works by binding to the topoisomerase I-DNA complex and preventing religation of these 328 single strand breaks.		2.0810pyranoindolizinoquinolineantineoplastic agent;
EC 5.99.1.2 (DNA topoisomerase) inhibitor
eliprodil
1-(4-chlorophenyl)-2-[4-(4-fluorobenzyl)piperidin-1-yl]ethanol : A member of the class of piperidines that is piperidine substituted by a 2-(4-chlorophenyl)-2-hydroxyethyl group at position 1 and by a 4-fluorobenzyl group at position 4.		2.0810monochlorobenzenes;
monofluorobenzenes;
piperidines;
secondary alcohol;
tertiary amino compound
celgosivir
celgosivir: inhibits glycoprotein processing & the growth of HIVs		2.610
gemcitabine
gemcitabine : A 2'-deoxycytidine having geminal fluoro substituents in the 2'-position. An inhibitor of ribonucleotide reductase, gemcitabine is used in the treatment of various carcinomas, particularly non-small cell lung cancer, pancreatic cancer, bladder cancer and breast cancer.		2.5820organofluorine compound;
pyrimidine 2'-deoxyribonucleoside		antimetabolite;
antineoplastic agent;
antiviral drug;
DNA synthesis inhibitor;
EC 1.17.4.1 (ribonucleoside-diphosphate reductase) inhibitor;
environmental contaminant;
immunosuppressive agent;
photosensitizing agent;
prodrug;
radiosensitizing agent;
xenobiotic
lamivudine
[no description available]		2.610monothioacetal;
nucleoside analogue;
oxacycle;
primary alcohol		allergen;
anti-HBV agent;
antiviral drug;
EC 2.7.7.49 (RNA-directed DNA polymerase) inhibitor;
HIV-1 reverse transcriptase inhibitor;
prodrug
valsartan
Valsartan: A tetrazole derivative and ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKER that is used to treat HYPERTENSION.. valsartan : A monocarboxylic acid amide consisting of L-valine in which the amino hydrogens have been replaced by a pentanoyl and a [2'-(1H-tetrazol-5-yl)biphenyl]-4-yl]methyl group. It exhibits antihypertensive activity.		2.610biphenylyltetrazole;
monocarboxylic acid amide;
monocarboxylic acid		angiotensin receptor antagonist;
antihypertensive agent;
environmental contaminant;
xenobiotic
zanamivir
Zanamivir: A guanido-neuraminic acid that is used to inhibit NEURAMINIDASE.		2.610guanidinesantiviral agent;
EC 3.2.1.18 (exo-alpha-sialidase) inhibitor
adefovir dipivoxil
bis(pivaloyloxymethyl)-9-(2-phosphonylmethoxyethyl)adenine: structure given in first source. adefovir pivoxil : An organic phosphonate that is the dipivoxil ester of adefovir. A prodrug for adefovir, an HIV-1 reverse transcriptase inhibitor, adefovir pivoxil is used to treat chronic hepatitis B viral infection.		2.6106-aminopurines;
carbonate ester;
ether;
organic phosphonate		antiviral drug;
DNA synthesis inhibitor;
HIV-1 reverse transcriptase inhibitor;
nephrotoxic agent;
prodrug
emtricitabine
Emtricitabine: A deoxycytidine analog and REVERSE TRANSCRIPTASE INHIBITOR with antiviral activity against HIV-1 and HEPATITIS B viruses. It is used to treat HIV INFECTIONS.. emtricitabine : An organofluorine compound that is 5-fluorocytosine substituted at the 1 position by a 2-(hydroxymethyl)-1,3-oxathiolan-5-yl group (2R,5S configuration). It is used in combination therapy for the treatment of HIV-1 infection.		2.610monothioacetal;
nucleoside analogue;
organofluorine compound;
pyrimidone		antiviral drug;
HIV-1 reverse transcriptase inhibitor
octyl gallate
[no description available]		2.610gallate esterfood antioxidant;
hypoglycemic agent;
plant metabolite
verapamil hydrochloride
verapamil hydrochloride : A racemate comprising equimolar amounts of dexverapamil hydrochloride and (S)-verapamil hydrochloride.		2.0810
efavirenz
efavirenz: HIV-1 reverse transcriptase inhibitor. efavirenz : 1,4-Dihydro-2H-3,1-benzoxazin-2-one substituted at the 4 position by cyclopropylethynyl and trifluoromethyl groups (S configuration) and at the 6 position by chlorine. A non-nucleoside reverse transcriptase inhibitor with activity against HIV, it is used with other antiretrovirals for combination therapy of HIV infection.		2.5820acetylenic compound;
benzoxazine;
cyclopropanes;
organochlorine compound;
organofluorine compound		antiviral drug;
HIV-1 reverse transcriptase inhibitor
nelfinavir
Nelfinavir: A potent HIV protease inhibitor. It is used in combination with other antiviral drugs in the treatment of HIV in both adults and children.. nelfinavir : An aryl sulfide that is used (as its mesylate salt) for treatment of HIV and also exhibits some anticancer properties.		2.610aryl sulfide;
benzamides;
organic heterobicyclic compound;
phenols;
secondary alcohol;
tertiary amino compound		antineoplastic agent;
HIV protease inhibitor
betulinic acid
[no description available]		2.610hydroxy monocarboxylic acid;
pentacyclic triterpenoid		anti-HIV agent;
anti-inflammatory agent;
antimalarial;
antineoplastic agent;
EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor;
plant metabolite
arctigenin
arctigenin: precursor to catechols; in many plants		2.610lignan
baicalin
[no description available]		2.610dihydroxyflavone;
glucosiduronic acid;
glycosyloxyflavone;
monosaccharide derivative		antiatherosclerotic agent;
antibacterial agent;
anticoronaviral agent;
antineoplastic agent;
antioxidant;
cardioprotective agent;
EC 2.7.7.48 (RNA-directed RNA polymerase) inhibitor;
EC 3.4.21.26 (prolyl oligopeptidase) inhibitor;
ferroptosis inhibitor;
neuroprotective agent;
non-steroidal anti-inflammatory drug;
plant metabolite;
prodrug
plerixafor
plerixafor: a bicyclam derivate, highly potent & selective inhibitor of HIV-1 & HIV-2. plerixafor : An azamacrocycle consisting of two cyclam rings connected by a 1,4-phenylenebis(methylene) linker. It is a CXCR4 chemokine receptor antagonist and a hematopoietic stem cell mobilizer. It is used in combination with grulocyte-colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells to the perpheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma and multiple myeloma.		420azacycloalkane;
azamacrocycle;
benzenes;
crown amine;
secondary amino compound;
tertiary amino compound		anti-HIV agent;
antineoplastic agent;
C-X-C chemokine receptor type 4 antagonist;
immunological adjuvant
amprenavir
[no description available]		2.610carbamate ester;
sulfonamide;
tetrahydrofuryl ester		antiviral drug;
HIV protease inhibitor
oseltamivir
Oseltamivir: An acetamido cyclohexene that is a structural homolog of SIALIC ACID and inhibits NEURAMINIDASE.. oseltamivir : A cyclohexenecarboxylate ester that is the ethyl ester of oseltamivir acid. An antiviral prodrug (it is hydrolysed to the active free carboxylic acid in the liver), it is used to slow the spread of influenza.		2.610acetamides;
amino acid ester;
cyclohexenecarboxylate ester;
primary amino compound		antiviral drug;
EC 3.2.1.18 (exo-alpha-sialidase) inhibitor;
environmental contaminant;
prodrug;
xenobiotic
epigallocatechin gallate
epigallocatechin gallate: a steroid 5alpha-reductase inhibitor and antimutagen in green tea (Camellia sinensis). (-)-epigallocatechin 3-gallate : A gallate ester obtained by the formal condensation of gallic acid with the (3R)-hydroxy group of (-)-epigallocatechin.		2.610flavans;
gallate ester;
polyphenol		antineoplastic agent;
antioxidant;
apoptosis inducer;
geroprotector;
Hsp90 inhibitor;
neuroprotective agent;
plant metabolite
1,2,3,4,6-pentakis-O-galloyl-beta-D-glucose
pentagalloylglucose: pentahydroxy gallic acid ester of glucose; a phytogenic antineoplastic agent and antibacterial agent. 1,2,3,4,6-pentakis-O-galloyl-beta-D-glucose : A galloyl-beta-D-glucose compound having five galloyl groups in the 1-, 2-, 3-, 4- and 6-positions.		2.610gallate ester;
galloyl beta-D-glucose		anti-inflammatory agent;
antineoplastic agent;
geroprotector;
hepatoprotective agent;
plant metabolite;
radiation protective agent;
radical scavenger
cephalotaxine
[no description available]		2.610benzazepine alkaloid fundamental parent;
benzazepine alkaloid;
cyclic acetal;
enol ether;
organic heteropentacyclic compound;
secondary alcohol;
tertiary amino compound
desipramine hydrochloride
desipramine hydrochloride : The hydrochloride salt of desipramine.		2.610hydrochloridedrug allergen
mefloquine hydrochloride
[no description available]		2.610hydrochloride
bendamustine
[no description available]		2.0810benzimidazoles
aloxistatin
aloxistatin: a membrane-permeable cysteine protease inhibitor. aloxistatin : An L-leucine derivative that is the amide obtained by formal condensation of the carboxy group of (2S,3S)-3-(ethoxycarbonyl)oxirane-2-carboxylic acid with the amino group of N-(3-methylbutyl)-L-leucinamide.		2.610epoxide;
ethyl ester;
L-leucine derivative;
monocarboxylic acid amide		anticoronaviral agent;
cathepsin B inhibitor
propazole
propazole: RN given refers to parent cpd; structure		2.610benzimidazoles
caroverine
caroverine: structure		2.0810quinoxaline derivative
cgs 9343b
[no description available]		2.0810benzimidazoles
prulifloxacin
prulifloxacin: structure given in first source		2.610fluoroquinolone antibiotic;
quinolone antibiotic
telmisartan
Telmisartan: A biphenyl compound and benzimidazole derivative that acts as an angiotensin II type 1 receptor antagonist. It is used in the management of HYPERTENSION.. telmisartan : A member of the class of benzimidazoles used widely in the treatment of hypertension.		2.5820benzimidazoles;
biphenyls;
carboxybiphenyl		angiotensin receptor antagonist;
antihypertensive agent;
EC 3.4.15.1 (peptidyl-dipeptidase A) inhibitor;
environmental contaminant;
xenobiotic
bergenin
bergenin: RN refers to (2R-(2alpha,3beta,4alpha,4aalpha,10bbeta))-isomer; structure		2.610trihydroxybenzoic acidmetabolite
2-methoxyestradiol
2-methoxy-17beta-estradiol : A 17beta-hydroxy steroid, being 17beta-estradiol methoxylated at C-2.		2.081017beta-hydroxy steroid;
3-hydroxy steroid		angiogenesis modulating agent;
antimitotic;
antineoplastic agent;
human metabolite;
metabolite;
mouse metabolite
triazoles
Triazoles: Heterocyclic compounds containing a five-membered ring with two carbon atoms and three nitrogen atoms with the molecular formula C2H3N3.. triazoles : An azole in which the five-membered heterocyclic aromatic skeleton contains three N atoms and two C atoms.		5.08211,2,3-triazole
zoledronic acid
Zoledronic Acid: An imidobisphosphonate inhibitor of BONE RESORPTION that is used for the treatment of malignancy-related HYPERCALCEMIA; OSTEITIS DEFORMANS; and OSTEOPOROSIS.. zoledronic acid : An imidazole compound having a 2,2-bis(phosphono)-2-hydroxyethane-1-yl substituent at the 1-position.		2.6101,1-bis(phosphonic acid);
imidazoles		bone density conservation agent
artemisinin
(+)-artemisinin : A sesquiterpene lactone obtained from sweet wormwood, Artemisia annua, which is used as an antimalarial for the treatment of multi-drug resistant strains of falciparum malaria.		2.610organic peroxide;
sesquiterpene lactone		antimalarial;
plant metabolite
brinzolamide
brinzolamide: an antiglaucoma agent		2.610sulfonamide;
thienothiazine		antiglaucoma drug;
EC 4.2.1.1 (carbonic anhydrase) inhibitor
dipropylacetamide
dipropylacetamide: structure. valpromide : A fatty amide derived from valproic acid.		2.610fatty amidegeroprotector;
metabolite;
teratogenic agent
oxprenolol hydrochloride
[no description available]		2.610
guanfacine hydrochloride
[no description available]		2.1510acetamidesgeroprotector
opipramol hydrochloride
[no description available]		2.610
moroxydine
[no description available]		2.610biguanides
alacepril
[no description available]		2.0810dipeptide;
thioacetate ester		EC 3.4.15.1 (peptidyl-dipeptidase A) inhibitor
thioxolone
tioxolone : A 1,3-benzoxathiole having a hydroxy substituent at the 6-position.		2.610benzoxathioleantiseborrheic
ubenimex
ubenimex: growth inhibitor		2.5820
honokiol
[no description available]		2.610biphenyls
nobiletin
nobiletin : A methoxyflavone that is flavone substituted by methoxy groups at positions 5, 6, 7, 8, 3' and 4' respectively.		2.610methoxyflavoneantineoplastic agent;
plant metabolite
lycorine
lycorine: from bulbs of LYCORIS & other plants; RN given refers to (1 alpha,2 beta)-isomer; structure in Merck Index, 9th ed, #5444. lycorine : An indolizidine alkaloid that is 3,12-didehydrogalanthan substituted by hydroxy groups at positions and 2 and a methylenedioxy group across positions 9 and 10. Isolated from Crinum asiaticum, it has been shown to exhibit antimalarial activity.		2.610indolizidine alkaloidanticoronaviral agent;
antimalarial;
plant metabolite;
protein synthesis inhibitor
leupeptin
[no description available]		2.610aldehyde;
tripeptide		bacterial metabolite;
calpain inhibitor;
cathepsin B inhibitor;
EC 3.4.21.4 (trypsin) inhibitor;
serine protease inhibitor
tetrandrine
tetrandrine: a bisbenzylisoquinoline that exhibits antifibrogenic activity		2.610bisbenzylisoquinoline alkaloid;
isoquinolines
calpeptin
[no description available]		2.610amino acid amide
fangchinoline
[no description available]		2.610aromatic ether;
bisbenzylisoquinoline alkaloid;
macrocycle		anti-HIV-1 agent;
anti-inflammatory agent;
antineoplastic agent;
antioxidant;
neuroprotective agent;
plant metabolite
maslinic acid
(2Alpha,3beta)-2,3-dihydroxyolean-12-en-28-oic acid: from Luehea divaricata and Agrimonia eupatoria		2.610dihydroxy monocarboxylic acid;
pentacyclic triterpenoid		anti-inflammatory agent;
antineoplastic agent;
antioxidant;
plant metabolite
atovaquone
Atovaquone: A hydroxynaphthoquinone that has antimicrobial activity and is being used in antimalarial protocols.. atovaquone : A naphthoquinone compound having a 4-(4-chlorophenyl)cyclohexyl group at the 2-position and a hydroxy substituent at the 3-position.		2.610hydroxy-1,2-naphthoquinone
2-Chloronicotinic acid
[no description available]		2.2510aromatic carboxylic acid;
pyridines
bendamustine hydrochloride
[no description available]		4.1120
clarithromycin
Clarithromycin: A semisynthetic macrolide antibiotic derived from ERYTHROMYCIN that is active against a variety of microorganisms. It can inhibit PROTEIN SYNTHESIS in BACTERIA by reversibly binding to the 50S ribosomal subunits. This inhibits the translocation of aminoacyl transfer-RNA and prevents peptide chain elongation.. clarithromycin : The 6-O-methyl ether of erythromycin A, clarithromycin is a macrolide antibiotic used in the treatment of respiratory-tract, skin and soft-tissue infections. It is also used to eradicate Helicobacter pylori in the treatment of peptic ulcer disease. It prevents bacteria from growing by interfering with their protein synthesis.		4.4811macrolide antibioticantibacterial drug;
environmental contaminant;
protein synthesis inhibitor;
xenobiotic
loganin
[no description available]		2.610beta-D-glucoside;
cyclopentapyran;
enoate ester;
iridoid monoterpenoid;
methyl ester;
monosaccharide derivative;
secondary alcohol		anti-inflammatory agent;
EC 3.1.1.7 (acetylcholinesterase) inhibitor;
EC 3.2.1.20 (alpha-glucosidase) inhibitor;
EC 3.4.23.46 (memapsin 2) inhibitor;
neuroprotective agent;
plant metabolite
moexipril
[no description available]		2.610peptide
aucubin
[no description available]		2.610organic molecular entitymetabolite
catalpol
[no description available]		2.610organic molecular entitymetabolite
lekoptin
(S)-verapamil : A 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile that has S configuration.		2.6102-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile
n-methyladenosine
N-methyladenosine: is a inhibitor of cell differentiation. N(6)-methyladenosine : A methyladenosine compound with one methyl group attached to N(6) of the adenine nucleobase.		2.610methyladenosine
vinpocetine
[no description available]		2.0810
sivelestat
sivelestat: inhibitor of neutrophil elastase; structure given in first source		2.610N-acylglycine;
pivalate ester
pyronaridine
[no description available]		2.610aminoquinoline
geniposide
[no description available]		2.610terpene glycoside
deguelin
deguelin: a natural product from Mundulea sericea; RN refers to (7aS-cis)-isomer; structure given in first source. deguelin : A rotenone that is 13,13a-dihydro-3H-chromeno[3,4-b]pyrano[2,3-h]chromen-7(7aH)-one substituted by methoxy groups at positions 9 and 10, and by two methyl groups at position 3 (the 7aS,13aS-stereoisomer). It exists in abundant quantities in the bark, roots, and leaves of the Leguminosae family of plants and reported to exert anti-tumour effects in various cancers.		2.0810aromatic ether;
diether;
organic heteropentacyclic compound;
rotenones		angiogenesis inhibitor;
anti-inflammatory agent;
antineoplastic agent;
antiviral agent;
apoptosis inducer;
EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor;
mitochondrial NADH:ubiquinone reductase inhibitor;
plant metabolite
daidzin
daidzin: a potent, selective, and reversible inhibitor of human mitochondrial aldehyde dehydrogenase. daidzein 7-O-beta-D-glucoside : A glycosyloxyisoflavone that is daidzein attached to a beta-D-glucopyranosyl residue at position 7 via a glycosidic linkage. It is used in the treatment of alcohol dependency (antidipsotropic).		2.6107-hydroxyisoflavones 7-O-beta-D-glucoside;
hydroxyisoflavone;
monosaccharide derivative		plant metabolite
triptolide
[no description available]		2.5520diterpenoid;
epoxide;
gamma-lactam;
organic heteroheptacyclic compound		antispermatogenic agent;
plant metabolite
sophocarpine
[no description available]		2.610
marimastat
marimastat: a matrix metalloproteinase inhibitor active in patients with advanced carcinoma of the pancreas, prostate, or ovary. marimastat : A secondary carboxamide resulting from the foraml condensation of the carboxy group of (2R)-2-[(1S)-1-hydroxy-2-(hydroxyamino)-2-oxoethyl]-4-methylpentanoic acid with the alpha-amino group of N,3-dimethyl-L-valinamide.		2.610hydroxamic acid;
secondary carboxamide		antineoplastic agent;
matrix metalloproteinase inhibitor
sr 48692
SR 48692: structure in first source; a neurotensin receptor-1 antagonist		2.0810N-acyl-amino acid
elacridar
Elacridar: inhibitor of MDR1 PROTEIN; structure given in first source		2.5820
celastrol
[no description available]		2.610monocarboxylic acid;
pentacyclic triterpenoid		anti-inflammatory drug;
antineoplastic agent;
antioxidant;
EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor;
Hsp90 inhibitor;
metabolite
imatinib mesylate
imatinib methanesulfonate : A methanesulfonate (mesylate) salt that is the monomesylate salt of imatinib. Used for treatment of chronic myelogenous leukemia and gastrointestinal stromal tumours.		2.7220methanesulfonate saltanticoronaviral agent;
antineoplastic agent;
apoptosis inducer;
tyrosine kinase inhibitor
gefitinib
[no description available]		2.0810aromatic ether;
monochlorobenzenes;
monofluorobenzenes;
morpholines;
quinazolines;
secondary amino compound;
tertiary amino compound		antineoplastic agent;
epidermal growth factor receptor antagonist
n-(n-(3-carboxyoxirane-2-carbonyl)leucyl)isoamylamine
N-(N-(3-carboxyoxirane-2-carbonyl)leucyl)isoamylamine: inhibits calcium-activated neutral protease; see also record for E-64; RN given refers to (2-S-(2alpha,3beta)(R*)-isomer)		2.610leucine derivative
bay x 1005
2-(4-(quinolin-2-yl-methoxy)phenyl)-2-cyclopentylacetic acid: inhibits synthesis of leukotriene B4 and 5-hydroxyeicosatetraenoic acid; inhibits five-lipoxygenase activating protein(FLAP)and leukotriene A4 hydrolase(LTA4H); structure given in first source;		2.0810
vadimezan
vadimezan : A monocarboxylic acid that is acetic acid in which one of the methyl hydrogens is replaced by a 5,6-dimethyl-9-oxoxanthen-4-yl group.		2.610monocarboxylic acid;
xanthones		antineoplastic agent
e 64
E 64: cysteine protease inhibitor of microbial origin, which inhibits cathepsin B (EC 3.4.22.1) and cathepsin L (EC 3.4.22.-)		2.610dicarboxylic acid monoamide;
epoxy monocarboxylic acid;
guanidines;
L-leucine derivative;
zwitterion		antimalarial;
antiparasitic agent;
protease inhibitor
gyki 53655
GYKI 53655: an AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate) receptor antagonist		2.0810
umifenovir
umifenovir: an antiviral agent		2.610indolyl carboxylic acid
safinamide
safinamide: short-acting inhibitor of MOA-B; FCE 26743 is (S)-isomer, FCE 28073 is (R)-isomer; structure in first source		2.610amino acid amide
ilomastat
CS 610: matrix metalloproteinase inhibitor; structure in first source. ilomastat : An N-acyl-amino acid obtained by formal condensation of the carboxy group of (2R)-2-[2-(hydroxyamino)-2-oxoethyl]-4-methylpentanoic acid with the amino group of N-methyl-L-tryptophanamide. A cell permeable broad-spectrum matrix metalloproteinase (MMP) inhibitor		2.610hydroxamic acid;
L-tryptophan derivative;
N-acyl-amino acid		anti-inflammatory agent;
antibacterial agent;
antineoplastic agent;
EC 3.4.24.24 (gelatinase A) inhibitor;
neuroprotective agent
ml-3000
[no description available]		2.0810
pomalidomide
3-aminophthalimidoglutarimide: structure in first source		9.3692aromatic amine;
dicarboximide;
isoindoles;
piperidones		angiogenesis inhibitor;
antineoplastic agent;
immunomodulator
cd 437
CD 437: selective for retinoic acid receptors gamma. CD437 : A naphthoic acid that is 6-phenylnaphthylene-2-carboxyic acid in which the phenyl substituent has been substituted at positions 3 and 4 by adamant-1-yl and hydroxy groups, respectively. It acts as a selective agonist of retinoic acid receptor (RAR)gamma and induces cell cycle arrest and apoptosis in various cancer cells.		2.0810adamantanes;
monocarboxylic acid;
naphthoic acid;
phenols		apoptosis inducer;
retinoic acid receptor gamma agonist
10-propargyl-10-deazaaminopterin
10-propargyl-10-deazaaminopterin: structure in first source. pralatrexate : A pteridine that is the N-4-[1-(2,4-diaminopteridin-6-yl)pent-4-yn-2-yl]benzoyl derivative of L-glutamic acid. Used for treatment of Peripheral T-Cell Lymphoma, an aggressive form of non-Hodgkins lymphoma.		2.1110N-acyl-L-glutamic acid;
pteridines;
terminal acetylenic compound		antimetabolite;
antineoplastic agent;
EC 1.5.1.3 (dihydrofolate reductase) inhibitor
docetaxel anhydrous
Docetaxel: A semisynthetic analog of PACLITAXEL used in the treatment of locally advanced or metastatic BREAST NEOPLASMS and NON-SMALL CELL LUNG CANCER.. docetaxel anhydrous : A tetracyclic diterpenoid that is paclitaxel with the N-benzyloxycarbonyl group replaced by N-tert-butoxycarbonyl, and the acetoxy group at position 10 replaced by a hydroxy group.		2.0810secondary alpha-hydroxy ketone;
tetracyclic diterpenoid		antimalarial;
antineoplastic agent;
photosensitizing agent
perifosine
[no description available]		3.5920ammonium betaine;
phospholipid		EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor
atazanavir
atazanavir : A heavily substituted carbohydrazide that is an antiretroviral drug of the protease inhibitor (PI) class used to treat infection of human immunodeficiency virus (HIV).		2.610carbohydrazideantiviral drug;
HIV protease inhibitor
mk 767
5-((2,4-dioxo-5-thiazolidinyl)methyl)-2-methoxy-N-((4-(trifluoromethyl)phenyl)methyl)benzamide: an antihyperlipidemic agent that also functions as an insulin sensitizer, PPARalpha agonist, and PPARgamma agonist; structure in first source		2.0810
vx 497
N-3-(3-(3-methoxy-4-oxazol-5-ylphenyl)ureido)benzylcarbamic acid tetrahydrofuran-3-yl ester: structure in first source		2.610
bcx 1812
[no description available]		2.6103-hydroxy monocarboxylic acid;
acetamides;
cyclopentanols;
guanidines		antiviral drug;
EC 3.2.1.18 (exo-alpha-sialidase) inhibitor
bazedoxifene acetate
[no description available]		2.0810
naproxen
Naproxen: An anti-inflammatory agent with analgesic and antipyretic properties. Both the acid and its sodium salt are used in the treatment of rheumatoid arthritis and other rheumatic or musculoskeletal disorders, dysmenorrhea, and acute gout.. naproxen : A methoxynaphthalene that is 2-methoxynaphthalene substituted by a carboxy ethyl group at position 6. Naproxen is a non-steroidal anti-inflammatory drug commonly used for the reduction of pain, fever, inflammation and stiffness caused by conditions such as osteoarthritis, kidney stones, rheumatoid arthritis, psoriatic arthritis, gout, ankylosing spondylitis, menstrual cramps, tendinitis, bursitis, and for the treatment of primary dysmenorrhea. It works by inhibiting both the COX-1 and COX-2 enzymes.		2.610methoxynaphthalene;
monocarboxylic acid		antipyretic;
cyclooxygenase 1 inhibitor;
cyclooxygenase 2 inhibitor;
drug allergen;
environmental contaminant;
gout suppressant;
non-narcotic analgesic;
non-steroidal anti-inflammatory drug;
xenobiotic
canertinib
[no description available]		2.0810monochlorobenzenes;
morpholines;
organofluorine compound;
quinazolines		antineoplastic agent;
tyrosine kinase inhibitor
birb 796
[no description available]		2.0810aromatic ether;
morpholines;
naphthalenes;
pyrazoles;
ureas		EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor;
immunomodulator
olmesartan
olmesartan: an active metabolite of CS 866		2.610biphenylyltetrazoleangiotensin receptor antagonist;
antihypertensive agent
telbivudine
[no description available]		2.610pyrimidine 2'-deoxyribonucleosideantiviral drug;
EC 2.7.7.49 (RNA-directed DNA polymerase) inhibitor
tipifarnib
[no description available]		2.0810imidazoles;
monochlorobenzenes;
primary amino compound;
quinolone		antineoplastic agent;
apoptosis inducer;
EC 2.5.1.58 (protein farnesyltransferase) inhibitor
celastrol methyl ester
celastrol methyl ester: isolated from Tripterygium wilfordii; potent inhibitory activity on both Kir2.1 and ERG1 potassium channels, leading to LONG QT SYNDROME		2.610carboxylic ester
resiquimod
S 28463: structure given in first source		2.610imidazoquinoline
cyc 202
seliciclib : 2,6-Diaminopurine carrying benzylamino, (2R)-1-hydroxybutan-2-yl and isopropyl substituents at C-6, C-2-N and N-9 respectively. It is an experimental drug candidate in the family of pharmacological cyclin-dependent kinase (CDK) inhibitors.		2.08102,6-diaminopurinesantiviral drug;
EC 2.7.11.22 (cyclin-dependent kinase) inhibitor
tanshinone ii a
tashinone IIA: a cardiovascular agent with antineoplastic activity; isolated from Salvia miltiorrhiza; structure in first source		2.610abietane diterpenoid
anacardic acid
anacardic acid: isolated from Anacardium occidentale; monophenol monooxygenase inhibitor. anacardic acid : A hydroxybenzoic acid that is salicylic acid substituted by a pentadecyl group at position 6. It is a major component of cashew nut shell liquid and exhibits an extensive range of bioactivities.		2.610hydroxy monocarboxylic acid;
hydroxybenzoic acid		anti-inflammatory agent;
antibacterial agent;
anticoronaviral agent;
apoptosis inducer;
EC 2.3.1.48 (histone acetyltransferase) inhibitor;
EC 3.4.22.69 (SARS coronavirus main proteinase) inhibitor;
neuroprotective agent;
plant metabolite
aminopterin
Aminopterin: A folic acid derivative used as a rodenticide that has been shown to be teratogenic.		2.1110dicarboxylic acidEC 1.5.1.3 (dihydrofolate reductase) inhibitor;
mutagen
carbobenzyloxyleucyl-tyrosine chloromethyl ketone
[no description available]		2.2510
migalastat
migalastat: a potent inhibitor of glycolipid biosynthesis		2.610piperidines
sb 203580
[no description available]		2.0810imidazoles;
monofluorobenzenes;
pyridines;
sulfoxide		EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor;
EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor;
geroprotector;
Hsp90 inhibitor;
neuroprotective agent
enzastaurin
[no description available]		2.0810indoles;
maleimides
erlotinib
[no description available]		2.5820aromatic ether;
quinazolines;
secondary amino compound;
terminal acetylenic compound		antineoplastic agent;
epidermal growth factor receptor antagonist;
protein kinase inhibitor
erlotinib hydrochloride
[no description available]		3.811hydrochloride;
terminal acetylenic compound		antineoplastic agent;
protein kinase inhibitor
piboserod
Serotonin 5-HT4 Receptor Antagonists: Drugs that bind to but do not activate SEROTONIN 5-HT4 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN RECEPTOR AGONISTS.		2.0810
l 163191
[no description available]		2.0810
limonin
[no description available]		2.610epoxide;
furans;
hexacyclic triterpenoid;
lactone;
limonoid;
organic heterohexacyclic compound		inhibitor;
metabolite;
volatile oil component
scutellarin
scutellarin: see scutellarein for aglycone. scutellarin : The glycosyloxyflavone which is the 7-O-glucuronide of scutellarein.		2.610glucosiduronic acid;
glycosyloxyflavone;
monosaccharide derivative;
trihydroxyflavone		antineoplastic agent;
proteasome inhibitor
bd 1047
N-(2-(3,4-Dichlorphenyl)ethyl)-N,N',N'-trimethyl-1,2-ethandiamin: sigma receptor ligand; putative sigma receptor antagonist with antidystonic activity		2.0810primary amine
etravirine
[no description available]		2.610aminopyrimidine;
aromatic ether;
dinitrile;
organobromine compound		antiviral agent;
HIV-1 reverse transcriptase inhibitor
chelidonine
chelidonine: benzophenanthridine derived from scoulerine from Chelidonium majus; RN given refers to parent cpd (chelidonine, (5bR-(5balpha,6beta,12alpha))-isomer)		2.610alkaloid antibiotic;
alkaloid fundamental parent;
benzophenanthridine alkaloid
4-n-butylresorcinol
4-n-butylresorcinol: structure in first source		2.610resorcinols
lapatinib
[no description available]		2.0810furans;
organochlorine compound;
organofluorine compound;
quinazolines		antineoplastic agent;
tyrosine kinase inhibitor
darunavir
Darunavir: An HIV PROTEASE INHIBITOR that is used in the treatment of AIDS and HIV INFECTIONS. Due to the emergence of ANTIVIRAL DRUG RESISTANCE when used alone, it is administered in combination with other ANTI-HIV AGENTS.. darunavir : An N,N-disubstituted benzenesulfonamide bearing an unsubstituted amino group at the 4-position, used for the treatment of HIV infection. A second-generation HIV protease inhibitor, darunavir was designed to form robust interactions with the protease enzyme from many strains of HIV, including those from treatment-experienced patients with multiple resistance mutations to other protease inhibitors.		2.610carbamate ester;
furofuran;
sulfonamide		antiviral drug;
HIV protease inhibitor
dapivirine
Dapivirine: effectively prevented human immunodeficiency virus (HIV) infection in cocultures of monocyte-derived dendritic cells and T cells, representing primary targets in sexual transmission		2.610
sorafenib
[no description available]		2.0810(trifluoromethyl)benzenes;
aromatic ether;
monochlorobenzenes;
phenylureas;
pyridinecarboxamide		angiogenesis inhibitor;
anticoronaviral agent;
antineoplastic agent;
EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor;
ferroptosis inducer;
tyrosine kinase inhibitor
lenalidomide
[no description available]		16.87227aromatic amine;
dicarboximide;
isoindoles;
piperidones		angiogenesis inhibitor;
antineoplastic agent;
immunomodulator
N-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxy-6-quinolinyl]-4-(dimethylamino)-2-butenamide
[no description available]		2.0810aminoquinoline
sr 142806
[no description available]		2.0810
gossypol acetic acid
[no description available]		2.110
nsc 74859
NSC 74859: inhibits Stat3 binding activity; structure in first source. S3I-201 : An amidobenzoic acid obtained by formal condensation of the carboxy group of [(4-methylbenzene-1-sulfonyl)oxy]acetic acid with the amino group of 4-amino-2-hydroxybenzoic acid.		2.610amidobenzoic acid;
monohydroxybenzoic acid;
tosylate ester		STAT3 inhibitor
berbamine
[no description available]		2.610bisbenzylisoquinoline alkaloid;
isoquinolines
elesclomol
[no description available]		2.0810carbohydrazide;
thiocarbonyl compound		antineoplastic agent;
apoptosis inducer
u-104
SLC-0111: a carbonic anhydrase inhibitor; structure in first source		2.610
7-hydroxy-5-methyl-2-(2-oxopropyl)-8-[3,4,5-trihydroxy-6-(hydroxymethyl)-2-oxanyl]-1-benzopyran-4-one
[no description available]		2.610glycoside
nsc 663284
NSC 663284: structure in first source		2.0810quinolone
bortezomib
[no description available]		15.01747amino acid amide;
L-phenylalanine derivative;
pyrazines		antineoplastic agent;
antiprotozoal drug;
protease inhibitor;
proteasome inhibitor
ritonavir
Ritonavir: An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV. It also inhibits CYTOCHROME P-450 CYP3A.. ritonavir : An L-valine derivative that is L-valinamide in which alpha-amino group has been acylated by a [(2-isopropyl-1,3-thiazol-4-yl)methyl]methylcarbamoyl group and in which a hydrogen of the carboxamide amino group has been replaced by a (2R,4S,5S)-4-hydroxy-1,6-diphenyl-5-{[(1,3-thiazol-5-ylmethoxy)carbonyl]amino}hexan-2-yl group. A CYP3A inhibitor and antiretroviral drug from the protease inhibitor class used to treat HIV infection and AIDS, it is often used as a fixed-dose combination with another protease inhibitor, lopinavir. Also used in combination with dasabuvir sodium hydrate, ombitasvir and paritaprevir (under the trade name Viekira Pak) for treatment of chronic hepatitis C virus genotype 1 infection as well as cirrhosis of the liver.		7.66201,3-thiazoles;
carbamate ester;
carboxamide;
L-valine derivative;
ureas		antiviral drug;
environmental contaminant;
HIV protease inhibitor;
xenobiotic
tizoxanide
tizoxanide: major metabolite of nitazoxanide; structure in first source		2.610salicylamides
bardoxolone methyl
methyl 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate: structure in first source		2.0810cyclohexenones
nsc 23766
[no description available]		2.0810aminopyrimidine;
aminoquinoline;
primary amino compound;
secondary amino compound;
tertiary amino compound		antiviral agent;
apoptosis inducer;
EC 3.6.5.2 (small monomeric GTPase) inhibitor;
muscarinic antagonist
gant 61
GANT 61: a sonic hedgehog pathway inhibitor and Gli inhibitor; structure in first source. GANT61 : An aminal that is hexahydropyrimidine which is substituted on each nitrogen by a 2-(dimethylamino)benzyl group, and at the aminal carbon by a pyridin-4-yl group. A Hedgehog signaling pathway and Gli protein inhibitor.		3.5110aminal;
dialkylarylamine;
pyridines;
substituted aniline;
tertiary amino compound		antineoplastic agent;
apoptosis inducer;
glioma-associated oncogene inhibitor;
Hedgehog signaling pathway inhibitor
carboplatin
[no description available]		9.8821
arbutin
hydroquinone O-beta-D-glucopyranoside : A monosaccharide derivative that is hydroquinone attached to a beta-D-glucopyranosyl residue at position 4 via a glycosidic linkage.		2.610beta-D-glucoside;
monosaccharide derivative		Escherichia coli metabolite;
plant metabolite
quinidine
Quinidine: An optical isomer of quinine, extracted from the bark of the CHINCHONA tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular ACTION POTENTIALS, and decreases automaticity. Quinidine also blocks muscarinic and alpha-adrenergic neurotransmission.. quinidine : A cinchona alkaloid consisting of cinchonine with the hydrogen at the 6-position of the quinoline ring substituted by methoxy.		2.610cinchona alkaloidalpha-adrenergic antagonist;
anti-arrhythmia drug;
antimalarial;
drug allergen;
EC 1.14.13.181 (13-deoxydaunorubicin hydroxylase) inhibitor;
EC 3.6.3.44 (xenobiotic-transporting ATPase) inhibitor;
muscarinic antagonist;
P450 inhibitor;
potassium channel blocker;
sodium channel blocker
conessine
conessine : A steroid alkaloid that is con-5-enine substituted by a N,N-dimethylamino group at position 3. It has been isolated from the plant species of the family Apocynaceae.		2.610steroid alkaloid;
tertiary amino compound		antibacterial agent;
antimalarial;
H3-receptor antagonist;
plant metabolite
saquinavir
Saquinavir: An HIV protease inhibitor which acts as an analog of an HIV protease cleavage site. It is a highly specific inhibitor of HIV-1 and HIV-2 proteases, and also inhibits CYTOCHROME P-450 CYP3A.. saquinavir : An aspartic acid derivative obtained by formal condensation of the primary amino group of (2S,3R)-4-[(3S,4aS,8aS)-3-(tert-butylcarbamoyl)octahydroisoquinolin-2(1H)-yl]-3-hydroxy-1-phenylbutan-2-ylamine with the carboxy group of N(2)(-quinolin-2-ylcarbonyl)-L-asparagine. An inhibitor of HIV-1 protease.		2.610L-asparagine derivative;
quinolines		antiviral drug;
HIV protease inhibitor
abacavir
abacavir: a carbocyclic nucleoside with potent selective anti-HIV activity. abacavir : A 2,6-diaminopurine that is (1S)-cyclopent-2-en-1-ylmethanol in which the pro-R hydrogen at the 4-position is substituted by a 2-amino-6-(cyclopropylamino)-9H-purin-9-yl group. A nucleoside analogue reverse transcriptase inhibitor (NRTI) with antiretroviral activity against HIV, it is used (particularly as the sulfate) with other antiretrovirals in combination therapy of HIV infection.		2.6102,6-diaminopurinesantiviral drug;
drug allergen;
HIV-1 reverse transcriptase inhibitor
linezolid
[no description available]		2.610acetamides;
morpholines;
organofluorine compound;
oxazolidinone		antibacterial drug;
protein synthesis inhibitor
cephaelin
cephaelin: do not confuse with cephalin of brain; after emetine this is the most important alkaloid of ipecac; protein synthesis inhibitor. cephaeline : A pyridoisoquinoline comprising emetam having a hydroxy group at the 6'-position and methoxy substituents at the 7'-, 10- and 11-positions.		2.610pyridoisoquinoline
(-)-usnic acid
(-)-usnic acid : The (-)-enantiomer of usnic acid.		2.610usnic acidEC 1.13.11.27 (4-hydroxyphenylpyruvate dioxygenase) inhibitor
acetylleucyl-leucyl-norleucinal
acetylleucyl-leucyl-norleucinal: a proteasome inhibitor. acetylleucyl-leucyl-norleucinal : A tripeptide composed of N-acetylleucyl, leucyl and norleucinal residues joined in sequence.		2.610aldehyde;
tripeptide		cysteine protease inhibitor
resveratrol
trans-resveratrol : A resveratrol in which the double bond has E configuration.		2.610resveratrolantioxidant;
phytoalexin;
plant metabolite;
quorum sensing inhibitor;
radical scavenger
tacrolimus
Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.. tacrolimus (anhydrous) : A macrolide lactam containing a 23-membered lactone ring, originally isolated from the fermentation broth of a Japanese soil sample that contained the bacteria Streptomyces tsukubaensis.		6.3131macrolide lactambacterial metabolite;
immunosuppressive agent
mycophenolic acid
Mycophenolic Acid: Compound derived from Penicillium stoloniferum and related species. It blocks de novo biosynthesis of purine nucleotides by inhibition of the enzyme inosine monophosphate dehydrogenase (IMP DEHYDROGENASE). Mycophenolic acid exerts selective effects on the immune system in which it prevents the proliferation of T-CELLS, LYMPHOCYTES, and the formation of antibodies from B-CELLS. It may also inhibit recruitment of LEUKOCYTES to sites of INFLAMMATION.. mycophenolate : A monocarboxylic acid anion resulting from the removal of a proton from the carboxy group of mycophenolic acid.. mycophenolic acid : A member of the class of 2-benzofurans that is 2-benzofuran-1(3H)-one which is substituted at positions 4, 5, 6, and 7 by methyl, methoxy, (2E)-5-carboxy-3-methylpent-2-en-1-yl, and hydroxy groups, respectively. It is an antibiotic produced by Penicillium brevi-compactum, P. stoloniferum, P. echinulatum and related species. An immunosuppressant, it is widely used (partiularly as its sodium salt and as the 2-(morpholin-4-yl)ethyl ester prodrug, mycophenolate mofetil) to prevent tissue rejection following organ transplants and for the treatment of certain autoimmune diseases.		3.21102-benzofurans;
gamma-lactone;
monocarboxylic acid;
phenols		anticoronaviral agent;
antimicrobial agent;
antineoplastic agent;
EC 1.1.1.205 (IMP dehydrogenase) inhibitor;
environmental contaminant;
immunosuppressive agent;
mycotoxin;
Penicillium metabolite;
xenobiotic
lycopene
[no description available]		2.610acyclic caroteneantioxidant;
plant metabolite
zithromax
Azithromycin: A semi-synthetic macrolide antibiotic structurally related to ERYTHROMYCIN. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis.. azithromycin : A macrolide antibiotic useful for the treatment of bacterial infections.		2.610macrolide antibioticantibacterial drug;
environmental contaminant;
xenobiotic
gw 3965
GW 3965: a liver X receptor ligand		2.0810diarylmethane
y 27632
Y 27632: RN given for di-HCl salt; inhibits Rho-associated protein kinase; inhibits calcium sensitization to affect smooth muscle relaxation; structure in first source. Y-27632 : A monocarboxylic acid amide that is trans-[(1R)-1-aminoethyl]cyclohexanecarboxamide in which one of the nitrogens of the aminocarbony group is substituted by a pyridine nucleus. It has been shown to exhibit inhibitory activity against Rho-associated protein kinase (ROCK) enzyme.		2.0810aromatic amide
6-bromoindirubin-3'-oxime
6-bromoindirubin-3'-oxime: structure in first source. 6-bromoindirubin-3'-oxime : A member of the class of biindoles that is indirubin substituted at position 6 by a bromo group and in which the keto group at position 3' has undergone condensation with hydroxylamine to form the corresponding oxime.		2.0810
purvalanol b
purvalanol B: protein kinase inhibitor; structure in first source		2.0810purvalanolprotein kinase inhibitor
y-700
[no description available]		2.0810
repsox
RepSox: inhibits TGF-beta signaling; structure in first source appears to be incorrect		2.0810pyrazolopyridine
roflumilast
[no description available]		2.610aromatic ether;
benzamides;
chloropyridine;
cyclopropanes;
organofluorine compound		anti-asthmatic drug;
phosphodiesterase IV inhibitor
L-cycloserine
L-cycloserine : A 4-amino-1,2-oxazolidin-3-one that has S configuration. An antibiotic isolated from Erwinia uredovora.		2.6104-amino-1,2-oxazolidin-3-oneanti-HIV agent;
anticonvulsant;
EC 2.3.1.50 (serine C-palmitoyltransferase) inhibitor
h 89
N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide: structure given in first source. N-[2-(4-bromocinnamylamino)ethyl]isoquinoline-5-sulfonamide : A member of the class of isoquinolines that is the sulfonamide obtained by formal condensation of the sulfo group of isoquinoline-5-sulfonic acid with the primary amino group of N(1)-[3-(4-bromophenyl)prop-2-en-1-yl]ethane-1,2-diamine. It is a protein kinase A inhibitor.. (E)-N-[2-(4-bromocinnamylamino)ethyl]isoquinoline-5-sulfonamide : A N-[2-(4-bromocinnamylamino)ethyl]isoquinoline-5-sulfonamide in which the double bond adopts a trans-configuration.		2.610N-[2-(4-bromocinnamylamino)ethyl]isoquinoline-5-sulfonamide
bevirimat
bevirimat: an HIV inhibitor; disrupts late step in processing HIV Major Core Protein p24, preventing the capsid precursor p25 from being converted to mature capsid p24. bevirimat : A pentacyclic triterpenoid obtained by the formal condensation of 2,2-dimethylsuccinic acid with the 3-hydroxy group of betulinic acid. It is isolated from the Chinese herb Syzygium claviflorum. The first in the class of HIV-1 maturation inhibitors to be studied in humans, bevirimat was identified as a potent HIV drug candidate and several clinical trials were conducted, but development into a new drug was plagued by numerous resistance-related problems.		2.610dicarboxylic acid monoester;
monocarboxylic acid;
pentacyclic triterpenoid		HIV-1 maturation inhibitor;
metabolite
benzyloxycarbonylleucyl-leucyl-leucine aldehyde
benzyloxycarbonylleucyl-leucyl-leucine aldehyde: proteasome inhibitor. N-benzyloxycarbonyl-L-leucyl-L-leucyl-L-leucinal : A tripeptide that is L-leucyl-L-leucyl-L-leucine in which the C-terminal carboxy group has been reduced to the corresponding aldehyde and the N-terminal amino group is protected as its benzyloxycarbonyl derivative.		2.6620amino aldehyde;
carbamate ester;
tripeptide		proteasome inhibitor
tenofovir
tenofovir (anhydrous) : A member of the class of phosphonic acids that is methylphosphonic acid in which one of the methyl hydrogens is replaced by a [(2R)-1-(6-amino-9H-purin-9-yl)propan-2-yl]oxy group. An inhibitor of HIV-1 reverse transcriptase, the bis(isopropyloxycarbonyloxymethyl) ester (disoproxil ester) prodrug is used as the fumaric acid salt in combination therapy for the treatment of HIV infection.		2.610nucleoside analogue;
phosphonic acids		antiviral drug;
drug metabolite;
HIV-1 reverse transcriptase inhibitor
posaconazole
[no description available]		2.610aromatic ether;
conazole antifungal drug;
N-arylpiperazine;
organofluorine compound;
oxolanes;
triazole antifungal drug;
triazoles		trypanocidal drug
gw 257406x
maribavir: has antiviral activity against human cytomegalovirus		2.610
shikonin
shikonin: a naphthazarin; has antineoplastic and angiogenesis inhibiting activities		2.610hydroxy-1,4-naphthoquinone
4,4-difluoro-N-[(1S)-3-[3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl]-1-phenylpropyl]-1-cyclohexanecarboxamide
[no description available]		2.5820tropane alkaloid
cmx 001
[no description available]		2.610
amd 8664
[no description available]		2.610
bay 41-4109
BAY 41-4109: structure in first source		2.610
bay 57-1293
pritelivir: herpes simplex virus 1 helicase-primase inhibitor		2.610
2'-c-methylcytidine
2'-C-methylcytidine: structure in first source		2.610
isoxanthohumol
isoxanthohumol: structure in first source		2.610flavanones
IPA-3
IPA-3 : An organic disulfide obtained by oxidative dimerisation of 1-sulfanylnaphthalen-2-ol.		2.2510naphthols;
organic disulfide		EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor
4-(4-chloro-2-methylphenoxy)-n-hydroxybutanamide
4-(4-chloro-2-methylphenoxy)-N-hydroxybutanamide: a c-FLIP inhibitor; structure in first source		2.610aromatic ether
mecarbinate
[no description available]		2.610
tenatoprazole
Tenatoprazole: structure in first source		2.1510imidazopyridine
s 1033
[no description available]		2.0810(trifluoromethyl)benzenes;
imidazoles;
pyridines;
pyrimidines;
secondary amino compound;
secondary carboxamide		anticoronaviral agent;
antineoplastic agent;
tyrosine kinase inhibitor
acetyl-aspartyl-glutamyl-valyl-aspartal
acetyl-aspartyl-glutamyl-valyl-aspartal: a capase inhibitor. Ac-Asp-Glu-Val-Asp-H : A tetrapeptide consisting of two L-aspartic acid residues, an L-glutamyl residue and an L-valine residue with an acetyl group at the N-terminal and with the C-terminal carboxy group reduced to an aldehyde. It is an inhibitor of caspase-3/7.		2.610tetrapeptideprotease inhibitor
octotropine methylbromide
octotropine methylbromide: minor descriptor (65-86); on line & INDEX MEDICUS search TROPANES (69-86); RN given refers to endo-isomer. anisotropine methylbromide : A quaternary ammonium salt resulting from the reaction of the amino group of anisotropine with methyl bromide.		2.610
fludarabine
[no description available]		2.110purine nucleoside
mercaptopurine
Mercaptopurine: An antimetabolite antineoplastic agent with immunosuppressant properties. It interferes with nucleic acid synthesis by inhibiting purine metabolism and is used, usually in combination with other drugs, in the treatment of or in remission maintenance programs for leukemia.. purine-6-thiol : A thiol that is the tautomer of mercaptopurine.. mercaptopurine : A member of the class of purines that is 6,7-dihydro-1H-purine carrying a thione group at position 6. An adenine analogue, it is used in the treatment of acute lymphocytic leukemia (ALL), chronic myeloid leukemia (CML), Crohn's disease, and ulcerative colitis.		2.5820aryl thiol;
purines;
thiocarbonyl compound		anticoronaviral agent;
antimetabolite;
antineoplastic agent
jrf 12
N2,N4-dibenzylquinazoline-2,4-diamine: a selective, potent, reversible, and ATP-competitive p97 inhibitor		2.610
3,4'-dihydroxyflavone
3,4'-dihydroxyflavone: an antioxidant; structure in first source		2.610
rg108
RG108: DNA methyltransferase inhibitor; structure in first source		2.0810indolyl carboxylic acid
3-(3,4-dimethoxyphenyl)propenoic acid
3-(3,4-dimethoxyphenyl)propenoic acid: structure given in first source; RN given refers to parent cpd. 3,4-dimethoxycinnamic acid : A methoxycinnamic acid that is trans-cinnamic acid substituted by methoxy groups at positions 3' and 4' respectively.		2.610methoxycinnamic acid
stf 083010
[no description available]		2.0810
isoferulic acid
isoferulic acid: isomer of ferulic acid; structure. isoferulic acid : A ferulic acid consisting of trans-cinnamic acid bearing methoxy and hydroxy substituents at positions 4 and 3 respectively on the phenyl ring.		2.610ferulic acidsantioxidant;
biomarker;
metabolite
N-(3-cyano-4,5,6,7-tetrahydro-1-benzothiophen-2-yl)-1-naphthalenecarboxamide
[no description available]		2.0810naphthalenecarboxamide
cyclouridine
cyclouridine: structure given in third source		2.610
curcumin
Curcumin: A yellow-orange dye obtained from tumeric, the powdered root of CURCUMA longa. It is used in the preparation of curcuma paper and the detection of boron. Curcumin appears to possess a spectrum of pharmacological properties, due primarily to its inhibitory effects on metabolic enzymes.. curcumin : A beta-diketone that is methane in which two of the hydrogens are substituted by feruloyl groups. A natural dyestuff found in the root of Curcuma longa.		2.610aromatic ether;
beta-diketone;
diarylheptanoid;
enone;
polyphenol		anti-inflammatory agent;
antifungal agent;
antineoplastic agent;
biological pigment;
contraceptive drug;
dye;
EC 1.1.1.205 (IMP dehydrogenase) inhibitor;
EC 1.1.1.21 (aldehyde reductase) inhibitor;
EC 1.1.1.25 (shikimate dehydrogenase) inhibitor;
EC 1.6.5.2 [NAD(P)H dehydrogenase (quinone)] inhibitor;
EC 1.8.1.9 (thioredoxin reductase) inhibitor;
EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor;
EC 3.5.1.98 (histone deacetylase) inhibitor;
flavouring agent;
food colouring;
geroprotector;
hepatoprotective agent;
immunomodulator;
iron chelator;
ligand;
lipoxygenase inhibitor;
metabolite;
neuroprotective agent;
nutraceutical;
radical scavenger
cct018159
CCT018159: structure in first source. CCT-018159 : A member of the class of pyrazoles that is 1H-pyrazole carrying 1,4-benzodioxane-6-yl and 5-ethyl-2,4-dihydroxyphenyl substituents at positions 4 and 5 respectively.		2.0810benzodioxine;
pyrazoles;
resorcinols		antineoplastic agent;
apoptosis inducer;
Hsp90 inhibitor
secinh3
SecinH3: a small molecule antagonist of cytohesins; structure in first source		2.0810triazoles
jk184
JK184: structure in first source		2.0810
zucapsaicin
[no description available]		2.610methoxybenzenes;
phenols
nbd 556
[no description available]		2.610
thioguanine anhydrous
Thioguanine: An antineoplastic compound which also has antimetabolite action. The drug is used in the therapy of acute leukemia.. tioguanine : A 2-aminopurine that is the 6-thiono derivative of 2-amino-1,9-dihydro-6H-purine. Incorporates into DNA and inhibits synthesis. Used in the treatment of leukaemia.		2.6102-aminopurinesanticoronaviral agent;
antimetabolite;
antineoplastic agent
4,5,6,7-tetrachloroindan-1,3-dione
4,5,6,7-tetrachloroindan-1,3-dione: inhibits ubiquitin C-terminal hydrolase L1		2.610
tamoxifen citrate
[no description available]		2.0810citrate saltangiogenesis inhibitor;
anticoronaviral agent
tamoxifen
[no description available]		2.1510stilbenoid;
tertiary amino compound		angiogenesis inhibitor;
antineoplastic agent;
bone density conservation agent;
EC 1.2.3.1 (aldehyde oxidase) inhibitor;
EC 2.7.11.13 (protein kinase C) inhibitor;
estrogen antagonist;
estrogen receptor antagonist;
estrogen receptor modulator
hc-067047
HC-067047: a TRPA1 antagonist; structure in first source		2.0810
bi-78d3
[no description available]		2.0810aryl sulfide
srpin340
SRPIN340: Serine-Arginine-Rich Protein Kinase Inhibitor		2.610
gsk 3787
[no description available]		2.0810
pr-619
[no description available]		2.610
p5091
P5091: inhibits ubiquitin-specific protease 7; structure in first source		420
methyl-thiohydantoin-tryptophan
methyl-thiohydantoin-tryptophan: structure in first source		2.0810organonitrogen compound;
organooxygen compound
2-[2-chloro-6-ethoxy-4-[(3-methyl-5-oxo-1-phenyl-4-pyrazolylidene)methyl]phenoxy]acetic acid methyl ester
[no description available]		2.0810monocarboxylic acid
4-(5-(4-methoxyphenyl)-3-phenyl-4,5-dihydro-1h-pyrazol-1-yl)benzenesulfonamide
[no description available]		2.0810sulfonamide
trovirdine
trovirdine: HIV-1 reverse transcriptase inhibitor		2.610
LSM-1318
[no description available]		2.0810oxa-steroid
fti 277
[no description available]		2.610
u 0126
U 0126: protein kinase kinase inhibitor; structure in first source		2.610aryl sulfide;
dinitrile;
enamine;
substituted aniline		antineoplastic agent;
antioxidant;
apoptosis inducer;
EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor;
osteogenesis regulator;
vasoconstrictor agent
rwj 67657
RWJ 67657: inhibits p38 mitogen-activated protein kinase; structure in first source		2.0810
vicriviroc
vicriviroc: structure in first source		2.610(trifluoromethyl)benzenes
telaprevir
[no description available]		2.610cyclopentapyrrole;
cyclopropanes;
oligopeptide;
pyrazines		antiviral drug;
hepatitis C protease inhibitor;
peptidomimetic
6-methyl-2-(phenylethynyl)pyridine
6-methyl-2-(phenylethynyl)pyridine: an mGlu5 antagonist. 2-methyl-6-(phenylethynyl)pyridine : A methylpyridine that coinsists of 2-methylp[yridine bearing an additional phenylethynyl group at position 6. Potent and highly selective non-competitive antagonist at the mGlu5 receptor subtype (IC50 = 36 nM) and a positive allosteric modulator at mGlu4 receptors. Centrally active following systemic administration in vivo. Reverses mechanical hyperalgesia in the inflamed rat hind paw.		2.0810acetylenic compound;
methylpyridines		anxiolytic drug;
metabotropic glutamate receptor antagonist
bms 387032
N-(5-(((5-(1,1-dimethylethyl)-2-oxazolyl)methyl)thio)-2-thiazolyl)-4-piperidinecarboxamide: a CDK2 inhibitor with antineoplastic activity; structure in first source. N-(5-{[(5-tert-butyl-1,3-oxazol-2-yl)methyl]sulfanyl}-1,3-thiazol-2-yl)piperidine-4-carboxamide : A secondary carboxamide resulting from the formal condensation of the carboxy group of piperidine-4-carboxylic acid with the amino group of 5-{[(5-tert-butyl-1,3-oxazol-2-yl)methyl]sulfanyl}-1,3-thiazol-2-amine. It is an ATP-competitive inhibitor of CDK2, CDK7 and CDK9 kinases and exhibits anti-cancer properties.		2.08101,3-oxazoles;
1,3-thiazoles;
organic sulfide;
piperidinecarboxamide;
secondary carboxamide		angiogenesis inhibitor;
antineoplastic agent;
apoptosis inducer;
EC 2.7.11.22 (cyclin-dependent kinase) inhibitor
orlistat
Orlistat: A lactone derivative of LEUCINE that acts as a pancreatic lipase inhibitor to limit the absorption of dietary fat; it is used in the management of obesity.. orlistat : A carboxylic ester resulting from the formal condensation of the carboxy group of N-formyl-L-leucine with the hydroxy group of (3S,4S)-3-hexyl-4-[(2S)-2-hydroxytridecyl]oxetan-2-one. A pancreatic lipase inhibitor, it is used as an anti-obesity drug.		2.610beta-lactone;
carboxylic ester;
formamides;
L-leucine derivative		anti-obesity agent;
bacterial metabolite;
EC 2.3.1.85 (fatty acid synthase) inhibitor;
EC 3.1.1.3 (triacylglycerol lipase) inhibitor
tandutinib
[no description available]		2.0810aromatic ether;
N-arylpiperazine;
N-carbamoylpiperazine;
phenylureas;
piperidines;
quinazolines;
tertiary amino compound		antineoplastic agent;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor
vx-745
[no description available]		2.0810aryl sulfide;
dichlorobenzene;
difluorobenzene;
pyrimidopyridazine		anti-inflammatory drug;
apoptosis inducer;
EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor
corlanor
ivabradine hydrochloride : A hydrochloride obtained by combining ivabradine with one molar equivalent of hydrochloric acid. Used to treat patients with angina who have intolerance to beta blockers and/or heart failure.		2.0810hydrochloridecardiotonic drug
dasatinib
N-(2-chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)-1,3-thiazole-5-carboxamide: a dasatinib prodrug; structure in first source. dasatinib (anhydrous) : An aminopyrimidine that is 2-methylpyrimidine which is substituted at position 4 by the primary amino group of 2-amino-1,3-thiazole-5-carboxylic acid and at position 6 by a 4-(2-hydroxyethyl)piperazin-1-yl group, and in which the carboxylic acid group has been formally condensed with 2-chloro-6-methylaniline to afford the corresponding amide. A multi-targeted kinase inhibitor, it is used, particularly as the monohydrate, for the treatment of chronic, accelerated, or myeloid or lymphoid blast phase chronic myeloid leukemia. Note that the name 'dasatinib' is used to refer to the monohydrate (USAN) as well as to anhydrous dasatinib (INN).		2.91301,3-thiazoles;
aminopyrimidine;
monocarboxylic acid amide;
N-(2-hydroxyethyl)piperazine;
N-arylpiperazine;
organochlorine compound;
secondary amino compound;
tertiary amino compound		anticoronaviral agent;
antineoplastic agent;
tyrosine kinase inhibitor
zd 6474
CH 331: structure in first source		2.0810aromatic ether;
organobromine compound;
organofluorine compound;
piperidines;
quinazolines;
secondary amine		antineoplastic agent;
tyrosine kinase inhibitor
compound 968
compound 968: a glutaminase inhibitor. 5-[3-bromo-4-(dimethylamino)phenyl]-2,2-dimethyl-2,3,5,6-tetrahydrobenzo[a]phenanthridin-4(1H)-one : A partially hydrogenated benzophenanthridine carrying an oxo group at C-4, geminal methyl groups at C-2 and a 3-bromo-4-(dimethylamino)phenyl group at C-5.		2.0810benzophenanthridineEC 3.5.1.2 (glutaminase) inhibitor
yya-021
YYA-021: an HIV entry inhibitor; structure in first source		2.610
sb-224289
SB 224289 : A member of the class of benzamides obtained by formal condensation of the carboxy group of 2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-carboxylic acid with the secondary amino group of 1'-methyl-6,7-dihydro-5H-spiro[furo[2,3-f]indole-3,4'-piperidine]. Selective 5-HT1B receptor antagonist (pKi = 8.2). Displays >60-fold selectivity over 5-HT1D, 5-HT1A, 5-HT1E, 5-HT1F, 5-HT2A and 5-HT2C receptors in radioligand binding and functional assays. Centrally active following oral administration in vivo.		2.08101,2,4-oxadiazole;
azaspiro compound;
benzamides;
organic heterotetracyclic compound		serotonergic antagonist
gw 7647
GW 7647: a PPAR-alpha agonist; structure in first source. GW 7647 : A monocarboxylic acid that is 2-(phenylsulfanyl)isobutyric acid in which the phenyl group is substituted at the para- position by a 3-aza-7-cyclohexylhept-1-yl group in which the nitrogen is acylated by a (cyclohexylamino)carbonyl group.		2.0810aryl sulfide;
monocarboxylic acid;
ureas		PPARalpha agonist
l 663536
MK-886: orally active leukotriene biosynthesis inhibitor. 3-[3-(tert-butylsulfanyl)-1-(4-chlorobenzyl)-5-(propan-2-yl)-1H-indol-2-yl]-2,2-dimethylpropanoic acid : A member of the class of indoles that is 1H-indole substituted by a isopropyl group at position 5, a tert-butylsulfanediyl group at position 3, a 4-chlorobenzyl group at position 1 and a 2-carboxy-2-methylpropyl group at position 2. It acts as an inhibitor of arachidonate 5-lipoxygenase.		2.0810aryl sulfide;
indoles;
monocarboxylic acid;
monochlorobenzenes		antineoplastic agent;
EC 1.13.11.34 (arachidonate 5-lipoxygenase) inhibitor;
leukotriene antagonist
1-[6-(4-chlorophenyl)-5-imidazo[2,1-b]thiazolyl]-N-[(3,4-dichlorophenyl)methoxy]methanimine
[no description available]		2.0810imidazoles
N4-ethyl-N6,1,2-trimethyl-N4-phenylpyrimidin-1-ium-4,6-diamine
[no description available]		2.0810aromatic amine;
tertiary amino compound
alpha-chymotrypsin
Chymotrypsin: A serine endopeptidase secreted by the pancreas as its zymogen, CHYMOTRYPSINOGEN and carried in the pancreatic juice to the duodenum where it is activated by TRYPSIN. It selectively cleaves aromatic amino acids on the carboxyl side.		2.5820
2-[[2-[2-(2,3-dihydro-1,4-benzodioxin-6-ylamino)-2-oxoethyl]-1-oxo-5-isoquinolinyl]oxy]propanoic acid ethyl ester
[no description available]		2.0810isoquinolines
sb 415286
3-(3-chloro-4-hydroxyphenylamino)-4-(4-nitrophenyl)-1H-pyrrole-2,5-dione: a glycogen synthase kinase-3 inhibitor; structure in first source		2.610C-nitro compound;
maleimides;
monochlorobenzenes;
phenols;
secondary amino compound;
substituted aniline		antioxidant;
apoptosis inducer;
EC 2.7.11.26 (tau-protein kinase) inhibitor;
neuroprotective agent
naphthoquinones
Naphthoquinones: Naphthalene rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.		2.3110
sch 79797
[no description available]		2.0810quinazolines
sitagliptin
sitagliptin : A triazolopyrazine that exhibits hypoglycemic activity.		2.610triazolopyrazine;
trifluorobenzene		EC 3.4.14.5 (dipeptidyl-peptidase IV) inhibitor;
environmental contaminant;
hypoglycemic agent;
serine proteinase inhibitor;
xenobiotic
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1h-imidazol-2-yl)benzamide
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide: a TGF-beta type I receptor kinase activity inhibitor		2.0810benzamides;
benzodioxoles;
imidazoles;
pyridines		EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor
1-(4-Fluorophenyl)-3-(3-(4-fluorophenyl)-3-hydroxypropyl)-4-(4-hydroxyphenyl)azetidin-2-one
[no description available]		2.0810monobactam
imd 0354
N-(3,5-bis(trifluoromethyl)phenyl)-5-chloro-2-hydroxybenzamide: a cardioprotective agent that inhibits IkappaB kinase beta (IKKbeta); structure in first source		2.0810benzamides
ex 527
6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide: structure in first source. 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide : A member of the class of carbazoles that is 2,3,4,9-tetrahydro-1H-carbazole which is substituted at position 1 by an aminocarbohyl group and at position 6 by a chlorine.		2.0810carbazoles;
monocarboxylic acid amide;
organochlorine compound
tak-220
TAK-220: structure in first source		2.610
jtk-303
[no description available]		2.610aromatic ether;
monochlorobenzenes;
organofluorine compound;
quinolinemonocarboxylic acid;
quinolone		HIV-1 integrase inhibitor
nbd 557
[no description available]		2.610
quercetin
[no description available]		2.08107-hydroxyflavonol;
pentahydroxyflavone		antibacterial agent;
antineoplastic agent;
antioxidant;
Aurora kinase inhibitor;
chelator;
EC 1.10.99.2 [ribosyldihydronicotinamide dehydrogenase (quinone)] inhibitor;
geroprotector;
phytoestrogen;
plant metabolite;
protein kinase inhibitor;
radical scavenger
5'-o-caffeoylquinic acid
trans-5-O-caffeoyl-D-quinic acid : A cinnamate ester obtained by formal condensation of the carboxy group of trans-caffeic acid with the 5-hydroxy group of quinic acid.		2.610cinnamate ester;
cyclitol carboxylic acid		plant metabolite
luteolin-7-glucoside
luteolin-7-glucoside: has both antiasthmatic and antineoplastic activities; has 3C protease inhibitory activity; isolated from Ligustrum lucidum. luteolin 7-O-beta-D-glucoside : A glycosyloxyflavone that is luteolin substituted by a beta-D-glucopyranosyl moiety at position 7 via a glycosidic linkage.		2.610beta-D-glucoside;
glycosyloxyflavone;
monosaccharide derivative;
trihydroxyflavone		antioxidant;
plant metabolite
cyclosporine
[no description available]		2.610
harmine
Harmine: Alkaloid isolated from seeds of PEGANUM HARMALA; ZYGOPHYLLACEAE. It is identical to banisterine, or telepathine, from Banisteria caapi and is one of the active ingredients of hallucinogenic drinks made in the western Amazon region from related plants. It has no therapeutic use, but (as banisterine) was hailed as a cure for postencephalitic PARKINSON DISEASE in the 1920's.. harmine : A harmala alkaloid in which the harman skeleton is methoxy-substituted at C-7.		2.610harmala alkaloidanti-HIV agent;
EC 1.4.3.4 (monoamine oxidase) inhibitor;
metabolite
genistein
[no description available]		2.08107-hydroxyisoflavonesantineoplastic agent;
EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor;
geroprotector;
human urinary metabolite;
phytoestrogen;
plant metabolite;
tyrosine kinase inhibitor
eprosartan
eprosartan: angiotensin II receptor antagonist. eprosartan : A member of the class of imidazoles and thiophenes that is an angiotensin II receptor antagonist used for the treatment of high blood pressure.		2.610dicarboxylic acid;
imidazoles;
thiophenes		angiotensin receptor antagonist;
antihypertensive agent;
environmental contaminant;
xenobiotic
mycophenolate mofetil
mycophenolate mofetil : A carboxylic ester resulting from the formal condensation between the carboxylic acid group of mycophenolic acid and the hydroxy group of 2-(morpholin-4-yl)ethanol. In the liver, it is metabolised to mycophenolic acid, an immunosuppressant for which it is a prodrug. It is widely used to prevent tissue rejection following organ transplants as well as for the treatment of certain autoimmune diseases.		2.610carboxylic ester;
ether;
gamma-lactone;
phenols;
tertiary amino compound		anticoronaviral agent;
EC 1.1.1.205 (IMP dehydrogenase) inhibitor;
immunosuppressive agent;
prodrug
entacapone
entacapone: structure given in first source. entacapone : A monocarboxylic acid amide that is N,N-diethylprop-2-enamide in which the hydrogen at position 2 is substituted by a cyano group and the hydrogen at the 3E position is substituted by a 3,4-dihydroxy-5-nitrophenyl group.		2.6102-nitrophenols;
catechols;
monocarboxylic acid amide;
nitrile		antidyskinesia agent;
antiparkinson drug;
central nervous system drug;
EC 2.1.1.6 (catechol O-methyltransferase) inhibitor
amentoflavone
[no description available]		2.610biflavonoid;
hydroxyflavone;
ring assembly		angiogenesis inhibitor;
antiviral agent;
cathepsin B inhibitor;
P450 inhibitor;
plant metabolite
baicalein
[no description available]		2.610trihydroxyflavoneangiogenesis inhibitor;
anti-inflammatory agent;
antibacterial agent;
anticoronaviral agent;
antifungal agent;
antineoplastic agent;
antioxidant;
apoptosis inducer;
EC 1.13.11.31 (arachidonate 12-lipoxygenase) inhibitor;
EC 1.13.11.33 (arachidonate 15-lipoxygenase) inhibitor;
EC 3.4.21.26 (prolyl oligopeptidase) inhibitor;
EC 3.4.22.69 (SARS coronavirus main proteinase) inhibitor;
EC 4.1.1.17 (ornithine decarboxylase) inhibitor;
ferroptosis inhibitor;
geroprotector;
hormone antagonist;
plant metabolite;
prostaglandin antagonist;
radical scavenger
genkwanin
genkwanin: structure. genkwanin : A monomethoxyflavone that is apigenin in which the hydroxy group at position 7 is methylated.		2.610dihydroxyflavone;
monomethoxyflavone		metabolite
hyperoside
quercetin 3-O-beta-D-galactopyranoside : A quercetin O-glycoside that is quercetin with a beta-D-galactosyl residue attached at position 3. Isolated from Artemisia capillaris, it exhibits hepatoprotective activity.		2.610beta-D-galactoside;
monosaccharide derivative;
quercetin O-glycoside;
tetrahydroxyflavone		hepatoprotective agent;
plant metabolite
mangostin
mangostin: xanthone from rind of Garcinia mangostana Linn. fruit. alpha-mangostin : A member of the class of xanthones that is 9H-xanthene substituted by hydroxy group at positions 1, 3 and 6, a methoxy group at position 7, an oxo group at position 9 and prenyl groups at positions 2 and 8. Isolated from the stems of Cratoxylum cochinchinense, it exhibits antioxidant, antimicrobial and antitumour activities.		2.610aromatic ether;
phenols;
xanthones		antimicrobial agent;
antineoplastic agent;
antioxidant;
plant metabolite
3-methylquercetin
isorhamnetin : A monomethoxyflavone that is quercetin in which the hydroxy group at position 3' is replaced by a methoxy group.		2.6107-hydroxyflavonol;
monomethoxyflavone;
tetrahydroxyflavone		anticoagulant;
EC 1.14.18.1 (tyrosinase) inhibitor;
metabolite
kaempferide
kaempferide: structure in first source. kaempferide : A monomethoxyflavone that is the 4'-O-methyl derivative of kaempferol.		2.6107-hydroxyflavonol;
monomethoxyflavone;
trihydroxyflavone		antihypertensive agent;
metabolite
orientin
orientin: structure given in first source; RN given refers to the (D-glucopyranosyl)-isomer. orientin : A C-glycosyl compound that is luteolin substituted by a beta-D-glucopyranosyl moiety at position 8.		2.6103'-hydroxyflavonoid;
C-glycosyl compound;
tetrahydroxyflavone		antioxidant;
metabolite
scutellarein
scutellarein: aglycone of scutellarin from Scutellaria baicalensis; carthamidin is 2S isomer of scutellarein; do not confuse with isoscutellarein and/or isocarthamidin which are respective regioisomers, or with the scutelarin protein. scutellarein : Flavone substituted with hydroxy groups at C-4', -5, -6 and -7.		2.610tetrahydroxyflavonemetabolite
trans-2,3',4,5'-tetrahydroxystilbene
trans-2,3',4,5'-tetrahydroxystilbene: hydroxystilbene oxyresveratrol		2.610stilbenoid
polydatin
trans-piceid : A stilbenoid that is trans-resveratrol substituted at position 3 by a beta-D-glucosyl residue.		2.610beta-D-glucoside;
monosaccharide derivative;
polyphenol;
stilbenoid		anti-arrhythmia drug;
antioxidant;
geroprotector;
hepatoprotective agent;
metabolite;
nephroprotective agent;
potassium channel modulator
chicoric acid
chicoric acid: inhibits HIV-1 integrase		2.610organooxygen compoundgeroprotector;
HIV-1 integrase inhibitor
acteoside
acteoside: a protein kinase C inhibitor with hepatoprotective, anti-asthmatic, and analgesic activities; a phenylethanoid glycoside related to isoacteoside; from leaves of Lippia multiflora (Verbenaceae). acteoside : A glycoside that is the alpha-L-rhamnosyl-(1->3)-beta-D-glucoside of hydroxytyrosol in which the hydroxy group at position 4 of the glucopyranosyl moiety has undergone esterification by formal condensation with trans-caffeic acid.		2.610catechols;
cinnamate ester;
disaccharide derivative;
glycoside;
polyphenol		anti-inflammatory agent;
antibacterial agent;
antileishmanial agent;
neuroprotective agent;
plant metabolite
dorzolamide
dorzolamide: topically effective ocular hypotensive carbonic anhydrase inhibitor; RN refers to mono-HCl (4S-trans)-isomer. dorzolamide : 5,6-Dihydro-4H-thieno[2,3-b]thiopyran-2-sulfonamide 7,7-dioxide in which hydrogens at the 4 and 6 positions are substituted by ethylamino and methyl groups, respectively (4S, trans-configuration). A carbonic anhydrase inhibitor, it is used as the hydrochloride in ophthalmic solutions to lower increased intraocular pressure in the treatment of open-angle glaucoma and ocular hypertension.		2.610sulfonamide;
thiophenes		antiglaucoma drug;
antihypertensive agent;
EC 4.2.1.1 (carbonic anhydrase) inhibitor
topiramate
Topiramate: A sulfamate-substituted fructose analog that was originally identified as a hypoglycemic agent. It is used for the treatment of EPILEPSY and MIGRAINE DISORDERS, and may also promote weight loss.. topiramate : A hexose derivative that is 2,3:4,5-di-O-isopropylidene-beta-D-fructopyranose in which the hydroxy group has been converted to the corresponding sulfamate ester. It blocks voltage-dependent sodium channels and is used as an antiepileptic and for the prevention of migraine.		2.610cyclic ketal;
ketohexose derivative;
sulfamate ester		anticonvulsant;
sodium channel blocker
fenretinide
Fenretinide: A synthetic retinoid that is used orally as a chemopreventive against prostate cancer and in women at risk of developing contralateral breast cancer. It is also effective as an antineoplastic agent.. 4-hydroxyphenyl retinamide : A retinoid obtained by formal condensation of the carboxy group of all-trans retinoic acid and the anilino group of 4-hydroxyaniline. Synthetic retinoid agonist. Antiproliferative, antioxidant and anticancer agent with a long half-life in vivo. Apoptotic effects appear to be mediated by a mechanism distinct from that of 'classical' retinoids.		2.0810monocarboxylic acid amide;
retinoid		antineoplastic agent;
antioxidant
ter 199
[no description available]		2.0810
arachidonylcyclopropylamide
arachidonylcyclopropylamide: a potent and selective agonist of neuronal cannabinoid receptor; structure in first source		2.0810
benzyloxycarbonyl-phe-ala-fluormethylketone
cathepsin B inhibitor : A cysteine protease inhibitor which inhibits cathepsin B (EC 3.4.22.1).		2.610
ly 320135
LY 320135: cannabinoid receptor antagonist; structure in first source		2.0810benzofurans
n-(n-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester
DAPT : A dipeptide consisting of alanylphenylglycine derivatised as a 3,5-difluorophenylacetamide at the amino terminal and a tert-butyl ester at the carboxy terminal. A gamma-secretase inhibitor.		2.610carboxylic ester;
difluorobenzene;
dipeptide;
tert-butyl ester		EC 3.4.23.46 (memapsin 2) inhibitor
pd 166285
[no description available]		2.0810
kn 62
KN 62: inhibitor of Ca/calmodulin-dependent protein kinase II		2.0810piperazines
su 6656
SU 6656: a c-Src kinase inhibitor; used to probe growth signaling; structure in first source. SU6656 : A member of the class of oxindoles that is 3-methyleneoxindole in which the hydrogeh at position 5 has been replaced by a dimethylaminosulfonyl group and in which one of the hydrogens of the methylene group has been replaced by a 4,5,6,7-tetrahydro-indol-2-yl group. It is a specific inhibitor of Src family kinase.		2.0810
casticin
casticin: from fruit of Vitex rotundifolia; structure in second source. casticin : A tetramethoxyflavone that consists of quercetagetin in which the hydroxy groups at positions 3, 6, 7 and 4' have been replaced by methoxy groups. It has been isolated from Eremophila mitchellii.		2.610dihydroxyflavone;
tetramethoxyflavone		apoptosis inducer;
plant metabolite
5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one
5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one: isolated from the Chinese herb Scutellariae radix. oroxylin A : A dihydroxy- and monomethoxy-flavone in which the hydroxy groups are positioned at C-5 and C-7 and the methoxy group is at C-6.		2.610dihydroxyflavone;
monomethoxyflavone		antineoplastic agent;
EC 1.14.13.39 (nitric oxide synthase) inhibitor
(E)-2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside
2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucopyranoside: Tyrosinase inhibitor from Polygonum multiflorum; structure in first source. (E)-2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside : A stilbenoid that is trans-stilbene which has been substituted by hydroxy groups at positions 2, 3, 5, and 4', and in which the hydroxy group at positon 2 has then been converted to the corresponding the beta-D-glucoside.		2.610beta-D-glucoside;
resorcinols;
stilbenoid		anti-inflammatory agent;
antioxidant;
apoptosis inhibitor;
cardioprotective agent;
cyclooxygenase 2 inhibitor;
platelet aggregation inhibitor
tyrphostin ag 555
[no description available]		2.610
semaxinib
semaxanib : An oxindole that is 3-methyleneoxindole in which one of the hydrogens of the methylene group is replaced by a 3,5-dimethylpyrrol-2-yl group.		2.0810olefinic compound;
oxindoles;
pyrroles		angiogenesis modulating agent;
antineoplastic agent;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor;
vascular endothelial growth factor receptor antagonist
su 11248
[no description available]		2.0810monocarboxylic acid amide;
pyrroles		angiogenesis inhibitor;
antineoplastic agent;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor;
immunomodulator;
neuroprotective agent;
vascular endothelial growth factor receptor antagonist
palbociclib
[no description available]		2.0810aminopyridine;
aromatic ketone;
cyclopentanes;
piperidines;
pyridopyrimidine;
secondary amino compound;
tertiary amino compound		antineoplastic agent;
EC 2.7.11.22 (cyclin-dependent kinase) inhibitor
jnj-7706621
[no description available]		2.0810sulfonamide
pd 151746
[no description available]		2.610
lisinopril
Lisinopril: One of the ANGIOTENSIN-CONVERTING ENZYME INHIBITORS (ACE inhibitors), orally active, that has been used in the treatment of hypertension and congestive heart failure.		2.610dipeptideEC 3.4.15.1 (peptidyl-dipeptidase A) inhibitor
verteporfin
(2R,2(1)S)-8-ethenyl-2(1),2(2)-bis(methoxycarbonyl)-17-(3-methoxy-3-oxopropyl)-2,7,12,18-tetramethyl-2,2(1)-dihydrobenzo[b]porphyrin-13-propanoic acid : The 2(1),2(2),17-trimethyl ester of (2R,2(1)S)-2(1),2(2)-dicarboxy-8-ethenyl-2,7,12,18-tetramethyl-2,2(1)-dihydrobenzo[b]porphyrin-13,17-dipropanoic acid.		2.610
batimastat
batimastat: structure given in first source; a synthetic matrix metalloproteinase inhibitor. batimastat : A secondary carboxamide resulting from the formal condensation of the carboxy group of (2S,3R)-5-methyl-3-{[(2S)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl]carbamoyl}-2-[(thiophen-2-ylsulfanyl)methyl]hexanoic acid with the amino group of hydroxylamine. It a broad-spectrum matrix metalloprotease inhibitor.		2.610hydroxamic acid;
L-phenylalanine derivative;
organic sulfide;
secondary carboxamide;
thiophenes;
triamide		angiogenesis inhibitor;
antineoplastic agent;
matrix metalloproteinase inhibitor
indinavir sulfate
Indinavir: A potent and specific HIV protease inhibitor that appears to have good oral bioavailability.		2.610dicarboxylic acid diamide;
N-(2-hydroxyethyl)piperazine;
piperazinecarboxamide		HIV protease inhibitor
cisplatin
[no description available]		2.0810diamminedichloroplatinumantineoplastic agent;
apoptosis inducer;
cross-linking reagent;
ferroptosis inducer;
genotoxin;
mutagen;
nephrotoxin;
photosensitizing agent
boron
Boron: A trace element with the atomic symbol B, atomic number 5, and atomic weight [10.806; 10.821]. Boron-10, an isotope of boron, is used as a neutron absorber in BORON NEUTRON CAPTURE THERAPY.		7.4110boron group element atom;
metalloid atom;
nonmetal atom		micronutrient
solanesol
solanesol : A nonaprenol that is hexatriaconta-2,6,10,14,18,22,26,30,34-nonaen-1-ol substituted by 9 methyl groups at positions 3, 7, 11, 15, 19, 23, 27, 31 and 35 (the all-trans0stereoisomer).		2.610nonaprenol;
primary alcohol		plant metabolite
pepstatin
pepstatin: inhibits the aspartic protease endothiapepsin		2.610pentapeptide;
secondary carboxamide		bacterial metabolite;
EC 3.4.23.* (aspartic endopeptidase) inhibitor
l 685458
L 685458: a gamma-secretase inhibitor; structure in first source. L-685,458 : A peptide and carboxamide that is L-leucyl-L-phenylalaninamide, L-Leu-L-Phe-NH2, which has been acylated on the N-terminus by a Phe-Phe hydroxyethylene dipeptide isotere, 2R-benzyl-5S-tert-butoxycarbonylamino-4R-hydroxy-6-phenylhexanoic acid. Compounds based on the structure of L-685,458 are potent inhibitors of gamma-secretase, which mediates the final catalytic step that generates the amyloid beta-peptide (Abeta), which assembles into the neurotoxic aggregates in the brains of sufferers of Alzheimer's disease.		2.610carbamate ester;
monocarboxylic acid amide;
peptide;
secondary alcohol		EC 3.4.23.46 (memapsin 2) inhibitor;
peptidomimetic
vx680
[no description available]		2.0810N-arylpiperazine
bms 806
BMS 806: prevents entry of HIV into cells by binding HIV envelope protein gp120; no further info available 4/2002		2.610
benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
[no description available]		2.610
tulobuterol hydrochloride
[no description available]		2.610organic molecular entity
salubrinal
salubrinal: prevents dephosphorylation of eIF2alpha; structure in first source. salubrinal : A member of the class of quinolines that is a mixed aminal resulting from the formal condensation oftrichloroacetaldehyde with the amide nitrogen of trans-cinnamamide and the primary amino group of 1-quinolin-8-ylthiourea. It is a selective inhibitor of cellular complexes that dephosphorylate eukaryotic translation initiation factor 2 subunit alpha (eIF2alpha).		2.610aminal;
organochlorine compound;
quinolines;
secondary carboxamide;
thioureas
d 4476
[no description available]		2.0810imidazoles
cyc 116
4-methyl-5-(2-(4-morpholinophenylamino)pyrimidin-4-yl)thiazol-2-amine: an aurora kinase inhibitor; structure in first source		2.0810
bay 19-8004
BAY 19-8004: a PDE4 inhibitor; structure in first source		2.0810
germacrone
germacrone: isolated from Curcuma wenyujin		2.610germacrane sesquiterpenoid;
olefinic compound		androgen antagonist;
anti-inflammatory agent;
antifeedant;
antifungal agent;
antimicrobial agent;
antineoplastic agent;
antioxidant;
antitussive;
antiviral agent;
apoptosis inducer;
autophagy inducer;
hepatoprotective agent;
insecticide;
neuroprotective agent;
plant metabolite;
volatile oil component
(2e,4e,6e,10e)-3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid
(2E,4E,6E,10E)-3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid: an acyclic retinoid that suppresses hepatocellular carcinoma recurrence; structure in first source		2.610
lithospermic acid
[no description available]		2.610
laq824
LAQ824: Histone deacetylase inhibitor		2.610
ekb 569
EKB 569: an EGF receptor kinase inhibitor		2.610aminoquinoline;
monocarboxylic acid amide;
monochlorobenzenes;
nitrile		protein kinase inhibitor
axitinib
[no description available]		2.0810aryl sulfide;
benzamides;
indazoles;
pyridines		antineoplastic agent;
tyrosine kinase inhibitor;
vascular endothelial growth factor receptor antagonist
pai 039
tiplaxtinin: inhibitor of plasminogen activator inhibitor-1		2.0810indole-3-acetic acids
rilpivirine
[no description available]		2.610aminopyrimidine;
nitrile		EC 2.7.7.49 (RNA-directed DNA polymerase) inhibitor;
HIV-1 reverse transcriptase inhibitor
(1Ar,7aS,10aS,10bS)-1a,5-dimethyl-8-methylidene-2,3,6,7,7a,8,10a,10b-octahydrooxireno[9,10]cyclodeca[1,2-b]furan-9(1aH)-one
[no description available]		2.610germacranolide
4,5-di-O-caffeoylquinic acid
[no description available]		2.610quinic acid
indigo carmine
3,5-di-O-(E)-caffeoylquinic acid: from roots of Lychnophora ericoides; structure in first source. 3,5-di-O-caffeoyl quinic acid : A carboxylic ester that is the diester obtained by the condensation of the hydroxy groups at positions 3 and 5 of (-)-quinic acid with the carboxy group of trans-caffeic acid. Isolated from Brazilian propolis and Suaeda glauca, it exhibits hepatoprotective and cytotoxic activities.		2.610
gw2974
GW2974: quinazoline derivative, which is able to block the activation of both the EGFR and erbB2		2.0810pyridopyrimidine
ispinesib
[no description available]		2.0810benzamides
fk 866
N-(4-(1-benzoylpiperidin-4-yl)butyl)-3-(pyridin-3-yl)acrylamide: inhibits nicotinamide phosphoribosyltransferase; structure in first source		2.3110benzamides;
N-acylpiperidine
artesunate
artesunic acid: RN given for (3R-(3alpha,5abeta,6beta,8abeta,9alpha,10alpha,12beta,(2aR*))-isomer; succinic ester of artemether		2.610artemisinin derivative;
cyclic acetal;
dicarboxylic acid monoester;
hemisuccinate;
semisynthetic derivative;
sesquiterpenoid		antimalarial;
antineoplastic agent;
ferroptosis inducer
temsirolimus
[no description available]		2.0810macrolide lactam
(3S,6S,9S,12R)-3-[(2S)-Butan-2-yl]-6-[(1-methoxyindol-3-yl)methyl]-9-(6-oxooctyl)-1,4,7,10-tetrazabicyclo[10.4.0]hexadecane-2,5,8,11-tetrone
[no description available]		2.610oligopeptide
pd 184352
2-(2-chloro-4-iodophenylamino)-N-cyclopropylmethoxy-3,4-difluorobenzamide: inhibits MAP kinase kinase; structure in first source		2.0810aminobenzoic acid
bibx 1382bs
BIBX 1382BS: an ErbB receptor kinase inhibitor; no further information available 4/2001		2.0810substituted aniline
vildagliptin
[no description available]		2.610amino acid amide
belinostat
[no description available]		7.7620hydroxamic acid;
olefinic compound;
sulfonamide		antineoplastic agent;
EC 3.5.1.98 (histone deacetylase) inhibitor
panobinostat
Panobinostat: An indole and hydroxamic acid derivative that acts as a HISTONE DEACETYLASE inhibitor. It is used as an antineoplastic agent in combination with BORTEZOMIB and DEXAMETHASONE for the treatment of MULTIPLE MYELOMA.. panobinostat : A hydroxamic acid obtained by formal condensation of the carboxy group of (2E)-3-[4-({[2-(2-methylindol-3-yl)ethyl]amino}methyl)phenyl]prop-2-enoic acid with the amino group of hydroxylamine. A histone deacetylase inhibitor used (as its lactate salt) in combination with bortezomib and dexamethasone for the treatment of multiple myeloma.		5.6760cinnamamides;
hydroxamic acid;
methylindole;
secondary amino compound		angiogenesis modulating agent;
antineoplastic agent;
EC 3.5.1.98 (histone deacetylase) inhibitor
hdac-42
HDAC-42: structure in first source		2.5820amidobenzoic acid
[4-[[4-(1-benzothiophen-2-yl)-2-pyrimidinyl]amino]phenyl]-[4-(1-pyrrolidinyl)-1-piperidinyl]methanone
[no description available]		2.0810benzamides;
N-acylpiperidine
chlorhexidine
Chlorhexidine: A disinfectant and topical anti-infective agent used also as mouthwash to prevent oral plaque.. chlorhexidine : A bisbiguanide compound with a structure consisting of two (p-chlorophenyl)guanide units linked by a hexamethylene bridge.		2.610biguanides;
monochlorobenzenes		antibacterial agent;
antiinfective agent
gs-7340
tenofovir alafenamide: component of Biktarvy. tenofovir alafenamide : An L-alanine derivative that is isopropyl L-alaninate in which one of the amino hydrogens is replaced by an (S)-({[(2R)-1-(6-amino-9H-purin-9-yl)propan-2-yl]oxy}methyl)(phenoxy)phosphoryl group. A prodrug for tenofovir, it is used (as the fumarate salt) in combination therapy for the treatment of HIV-1 infection.		2.6106-aminopurines;
ether;
isopropyl ester;
L-alanine derivative;
phosphoramidate ester		antiviral drug;
HIV-1 reverse transcriptase inhibitor;
prodrug
dexlansoprazole
Dexlansoprazole: The R-isomer of lansoprazole that is used to treat severe GASTROESOPHAGEAL REFLUX DISEASE.		2.1510benzimidazoles;
sulfoxide
iniparib
[no description available]		2.5820carbonyl compound;
organohalogen compound
n-(2-amino-5-fluorobenzyl)-4-(n-(pyridine-3-acrylyl)aminomethyl)benzamide
[no description available]		2.610
pri-2205
[no description available]		2.610
mk 0752
[no description available]		2.5820
gw 501516
GW 501516: a selective PPARdelta agonist; structure in first source. GW 501516 : An aromatic ether that is phenoxyacetic acid in which the phenyl group is substituted at position 2 by a methyl group and at position 4 by a (1,3-thiazol-5-ylmethyl)sulfanediyl group, and in which the 1,3-thiazolyl group is substituted at positions 2 and 4 by p-trifluoromethylphenyl and methyl groups, respectively.		2.08101,3-thiazoles;
aromatic ether;
aryl sulfide;
monocarboxylic acid;
organofluorine compound		carcinogenic agent;
PPARbeta/delta agonist
givinostat
[no description available]		2.610carbamate ester
av 412
[no description available]		2.0810
ag-041r
AG-041R: structure in first source		2.0810
telatinib
[no description available]		2.0810
cp 547632
3-(4-bromo-2,6-difluorobenzyloxy)-5-(3-(4-pyrrolidin-1-ylbutyl)ureido)isothiazole-4-carboxylic acid amide: inhibits vascular endothelial growth factor receptor-2 tyrosine kinase; structure in first source		2.0810
pd 144418
[no description available]		2.610
spc-839
SPC-839: an inhibitor of activator protein 1; structure in first source		2.0810
bicyclol
bicyclol: an antihepatitis drug, on the metabolism and hepatotoxicity of aflatoxin B1 (AFB1) in rats.		2.610
lenvatinib
lenvatinib : A member of the class of quinolines that is the carboxamide of 4-{3-chloro-4-[(cyclopropylcarbamoyl)amino]phenoxy}-7-methoxyquinoline-6-carboxylic acid. A multi-kinase inhibitor and orphan drug used (as its mesylate salt) for the treatment of various types of thyroid cancer that do not respond to radioiodine.		2.0810aromatic amide;
aromatic ether;
cyclopropanes;
monocarboxylic acid amide;
monochlorobenzenes;
phenylureas;
quinolines		antineoplastic agent;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor;
fibroblast growth factor receptor antagonist;
orphan drug;
vascular endothelial growth factor receptor antagonist
andarine
[no description available]		2.0810acetamides;
anilide
gw843682x
[no description available]		2.0810(trifluoromethyl)benzenes
pd 0325901
mirdametinib: has antineoplastic activity; appears to be a MEK inhibitor. PD 0325901 : A hydroxamic acid ester that is benzhydroxamic acid (N-hydroxybenzamide) in which the hydroxamic acid group has been converted to the corresponding 2,3-dihydroxypropyl ester and in which the benzene ring has been substituted at position 2 by a (2-fluoro-4-iodophenyl)amino group and at positions 3 and 4 by fluorines (the R enantiomer).		2.0810difluorobenzene;
hydroxamic acid ester;
monofluorobenzenes;
organoiodine compound;
propane-1,2-diols;
secondary amino compound		antineoplastic agent;
EC 2.7.12.2 (mitogen-activated protein kinase kinase) inhibitor
midostaurin
midostaurin : An organic heterooctacyclic compound that is the N-benzoyl derivative of staurosporine.		2.5820benzamides;
gamma-lactam;
indolocarbazole;
organic heterooctacyclic compound		antineoplastic agent;
EC 2.7.11.13 (protein kinase C) inhibitor
ag 14361
[no description available]		2.0810benzimidazoles
sb 265610
[no description available]		2.0810
ly 450139
[no description available]		2.610peptide
fr 148083
5Z-7-oxozeaenol : A macrolide that is the 7-oxo derivative of zeaenol (the 5Z stereoisomer). Isolated from Fungi, it exhibits cytotoxic, antibacterial and inhibitory activity against NF-kappaB.		2.0810aromatic ether;
macrolide;
phenols;
secondary alcohol;
secondary alpha-hydroxy ketone		antibacterial agent;
antineoplastic agent;
metabolite;
NF-kappaB inhibitor
mocetinostat
mocetinostat: undergoing phase II clinical trials for treatment of cancer. mocetinostat : A benzamide obtained by formal condensation of the carboxy group of 4-({[4-(pyridin-3-yl)pyrimidin-2-yl]amino}methyl)benzoic acid with one of the amino groups of benzene-1,2-diamine. It is an orally active and isotype-selective HDAC inhibitor which exhibits antitumour activity (IC50 = 0.15, 0.29, 1.66 and 0.59 muM for HDAC1, HDAC2, HDAC3 and HDAC11).		2.5820aminopyrimidine;
benzamides;
pyridines;
secondary amino compound;
secondary carboxamide;
substituted aniline		antineoplastic agent;
apoptosis inducer;
autophagy inducer;
cardioprotective agent;
EC 3.5.1.98 (histone deacetylase) inhibitor;
hepatotoxic agent
osi 930
OSI 930: inhibits both receptor tyrosine kinase Kit and kinase insert domain receptor; structure in first source		2.0810aromatic amide
ki 20227
[no description available]		2.0810
scio-469
SCIO-469: a small-molecule p38 mitogen-activated protein (MAP) kinase inhibitor for potential oral therapy for inflammatory disorders; in phase lib clinical trials for rheumatoid arthritis 4/2004. talmapimod : An indolecarboxamide obtained by formal condensation of the carboxy group of 6-chloro-3-[(dimethylamino)(oxo)acetyl]-1-methylindole-5-carboxylic acid with the secondary amino group of (2S,5R)-1-[(4-fluorophenyl)methyl]-2,5-dimethylpiperazine. It is a potent inhibitor of MAPK and exhibits anti-cancer properties.		2.0810aromatic amide;
aromatic ketone;
chloroindole;
dicarboxylic acid diamide;
indolecarboxamide;
monofluorobenzenes;
N-acylpiperazine;
N-alkylpiperazine		antineoplastic agent;
apoptosis inducer;
EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor
ssr 69071
SSR 69071: structure in first source		2.0810pyridopyrimidine
rivaroxaban
Rivaroxaban: A morpholine and thiophene derivative that functions as a FACTOR XA INHIBITOR and is used in the treatment and prevention of DEEP-VEIN THROMBOSIS and PULMONARY EMBOLISM. It is also used for the prevention of STROKE and systemic embolization in patients with non-valvular ATRIAL FIBRILLATION, and for the prevention of atherothrombotic events in patients after an ACUTE CORONARY SYNDROME.. rivaroxaban : A monocarboxylic acid amide obtained by formal condensation of the carboxy group of 5-chlorothiophene-2-carboxylic acid with the amino group of 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl}morpholin-3-one. An anticoagulant used for prophylaxis of venous thromboembolism in patients with knee or hip replacement surgery.		2.610aromatic amide;
lactam;
monocarboxylic acid amide;
morpholines;
organochlorine compound;
oxazolidinone;
thiophenes		anticoagulant;
EC 3.4.21.6 (coagulation factor Xa) inhibitor
sb 3ct compound
SB 3CT compound: a matrix metalloproteinase-2 inhibitor; structure in first source		2.610aromatic ether
pi103
PI103: pyridofuropyrimidine antineoplastic; a potent inhibitor of class I phosphatidylinositide 3-kinases (PI3K); structure in first soruce		2.0810aromatic amine;
morpholines;
organic heterotricyclic compound;
phenols;
tertiary amino compound		antineoplastic agent;
EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor;
mTOR inhibitor
sb 210313
[no description available]		2.0810
gw 4064
[no description available]		2.0810stilbenoid
ginsenoside rb1
[no description available]		2.610ginsenoside;
glycoside;
tetracyclic triterpenoid		anti-inflammatory drug;
anti-obesity agent;
apoptosis inhibitor;
neuroprotective agent;
plant metabolite;
radical scavenger
sa 4503
[no description available]		2.0810
ic 87114
IC 87114: structure in first source		2.08106-aminopurines;
biaryl;
quinazolines		EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor
zibotentan
ZD4054: a potent endothelin receptor A antagonist that inhibits ovarian carcinoma cell proliferation		2.0810phenylpyridine
mcc-950
[no description available]		2.4110
tivozanib
N-(2-chloro-4-((6,7-dimethoxy-4-quinolyl)oxy)phenyl)-N'-(5-methyl-3-isoxazolyl)urea: KNR-951 is the HCl, monohydrate salt; an antineoplastic agent; structure in first source		2.0810aromatic ether
hki 272
[no description available]		2.0810nitrile;
quinolines		antineoplastic agent;
tyrosine kinase inhibitor
tofacitinib
tofacitinib : A pyrrolopyrimidine that is pyrrolo[2,3-d]pyrimidine substituted at position 4 by an N-methyl,N-(1-cyanoacetyl-4-methylpiperidin-3-yl)amino moiety. Used as its citrate salt to treat moderately to severely active rheumatoid arthritis.		2.0810N-acylpiperidine;
nitrile;
pyrrolopyrimidine;
tertiary amino compound		antirheumatic drug;
EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor
bibr 1532
[no description available]		2.0810
n-(6-chloro-7-methoxy-9h-beta-carbolin-8-yl)-2-methylnicotinamide
[no description available]		2.0810
rucaparib
AG14447: Poly(ADP-ribose) polymerase inhibitor; structure in first source		2.5820azepinoindole;
caprolactams;
organofluorine compound;
secondary amino compound		antineoplastic agent;
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor
cediranib
[no description available]		2.0810aromatic ether
gw0742
GW 610742: structure in first source		2.0810monocarboxylic acid
6h-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetamide, 4-(4-chlorophenyl)-n-(4-hydroxyphenyl)-2,3,9-trimethyl-, (6s)-
[no description available]		2.610organonitrogen heterocyclic compound;
organosulfur heterocyclic compound
ps1145
PS1145: IkappaB kinase inhibitor; structure in first source		2.0810beta-carbolines
cetilistat
cetilistat: lipase inhibitor in randomized, placebo-controlled study of weight reduction in obese patients (3/2007)		2.610benzoxazine
bay 41-8543
BAY 41-8543: structure in first source		2.0810pyrazolopyridine
chir 99021
Chir 99021: structure in first source. CHIR 99021 : A member of the class of aminopyrimidines that is 2-aminopyrimidine substituted at positions N2, 5 and 6 by (5-cyanopyridin-2-yl)ethyl, 4-methylimidazol-2-yl and 2,4-dichlorophenyl groups respectively.		2.0810aminopyridine;
aminopyrimidine;
cyanopyridine;
diamine;
dichlorobenzene;
imidazoles;
secondary amino compound		EC 2.7.11.26 (tau-protein kinase) inhibitor
ym 201636
6-amino-N-(3-(4-(4-morpholinyl)pyrido(3',2'-4,5)furo(3,2-d)pyrimidin-2-yl)phenyl)-3-pyridinecarboxamide: an antiviral agent; structure in first source		2.610aromatic amide
sb 525334
6-(2-tert-butyl-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline: a TGF-betaR kinase inhibitor		2.0810quinoxaline derivative
way-362450
[no description available]		2.0810indoles
masitinib
[no description available]		2.08101,3-thiazoles;
benzamides;
N-alkylpiperazine;
pyridines		antineoplastic agent;
antirheumatic drug;
tyrosine kinase inhibitor
bx795
BX795: structure in first source		2.0810ureas
linagliptin
Linagliptin: A purine and quinazoline derivative that functions as an INCRETIN and DIPEPTIDYL-PEPTIDASE IV INHIBTOR. It is used as a HYPOGLYCEMIC AGENT in the treatment of TYPE II DIABETES MELLITUS.. linagliptin : A xanthine that is 7H-xanthine bearing (4-methylquinazolin-2-yl)methyl, methyl, but-2-yn-1-yl and 3-aminopiperidin-1-yl substituents at positions 1, 3, 7 and 8 respectively (the R-enantiomer). Used for treatment of type II diabetes.		2.610aminopiperidine;
quinazolines		EC 3.4.14.5 (dipeptidyl-peptidase IV) inhibitor;
hypoglycemic agent
pazopanib
pazopanib: a protein kinase inhibitor. pazopanib : A pyrimidine that is 5-(pyrimidin-2-yl}amino-2-methylbenzenesulfonamide substituted at position 4 by a (2,3-dimethylindazol-6-yl)(methyl)amino group. Used as its hydrochloride salt for treatment of kidney cancer.		8.9321aminopyrimidine;
indazoles;
sulfonamide		angiogenesis modulating agent;
antineoplastic agent;
tyrosine kinase inhibitor;
vascular endothelial growth factor receptor antagonist
sepantronium
sepantronium: a survivin suppressant with antineoplastic activity. sepantronium : An organic cation that is 1-(2-methoxyethyl)-2-methyl-1H-naphtho[2,3-d]imidazole-4,9-dione in which the nitrogen at position 3 of the napthoimidazole moiety has been alkylated by a pyrazin-2-ylmethyl group.		2.5520organic cation
azd 6244
AZD 6244: a MEK inhibitor		2.5820benzimidazoles;
bromobenzenes;
hydroxamic acid ester;
monochlorobenzenes;
organofluorine compound;
secondary amino compound		anticoronaviral agent;
antineoplastic agent;
EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor
odanacatib
odanacatib: a selective inhibitor of cathepsin K for the treatment of post-menopausal osteoporosis; structure in first source		2.610
1-(2-(1-adamantyl)ethyl)-1-pentyl-3-(3-(4-pyridyl)propyl)urea
1-(2-(1-adamantyl)ethyl)-1-pentyl-3-(3-(4-pyridyl)propyl)urea: structure in first source		2.0810
apilimod
[no description available]		2.610
apixaban
[no description available]		2.610aromatic ether;
lactam;
piperidones;
pyrazolopyridine		anticoagulant;
EC 3.4.21.6 (coagulation factor Xa) inhibitor
N-(3-cyanophenyl)-2'-methyl-5'-(5-methyl-1,3,4-oxadiazol-2-yl)biphenyl-4-carboxamide
N-(3-cyanophenyl)-2'-methyl-5'-(5-methyl-1,3,4-oxadiazol-2-yl)biphenyl-4-carboxamide : A member of the class of biphenyls that is the amide obtained by formal condensation of the carboxy group of 2'-methyl-5'-(5-methyl-1,3,4-oxadiazol-2-yl)[1,1'-biphenyl]-4-carboxylic acid with the amino group of 3-cyanoaniline.		2.08101,3,4-oxadiazoles;
benzamides;
biphenyls;
nitrile		EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor
ar c155858
AR C155858: an MCT1 inhibitor; structure in first source		2.0810
betrixaban
betrixaban: a highly potent, selective, and orally efficacious factor Xa inhibitor; structure in first source. betrixaban : A secondary carboxamide obtained by formal condensation of the carboxy group of 4-(N,N-dimethylcarbamimidoyl)benzoic acid with the amino group of 2-amino-N-(5-chloropyridin-2-yl)-5-methoxybenzamide. A synthetic anticoagulant compound that targets activated factor Xa in the coagulation cascade.		2.610benzamides;
guanidines;
monochloropyridine;
monomethoxybenzene;
secondary carboxamide		anticoagulant;
EC 3.4.21.6 (coagulation factor Xa) inhibitor
edoxaban
edoxaban : A monocarboxylic acid amide that is used (as its tosylate monohydrate) for the treatment of deep vein thrombosis and pulmonary embolism.		2.6620chloropyridine;
monocarboxylic acid amide;
tertiary amino compound;
thiazolopyridine		anticoagulant;
EC 3.4.21.6 (coagulation factor Xa) inhibitor;
platelet aggregation inhibitor
aee 788
AEE 788: structure in first source		2.08106-{4-[(4-ethylpiperazin-1-yl)methyl]phenyl}-N-(1-phenylethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amineangiogenesis inhibitor;
antineoplastic agent;
apoptosis inducer;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor;
epidermal growth factor receptor antagonist;
trypanocidal drug
saracatinib
[no description available]		2.930aromatic ether;
benzodioxoles;
diether;
N-methylpiperazine;
organochlorine compound;
oxanes;
quinazolines;
secondary amino compound		anticoronaviral agent;
antineoplastic agent;
apoptosis inducer;
autophagy inducer;
EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor;
radiosensitizing agent
sd-208
[no description available]		2.0810
n-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide
boceprevir : A synthetic tripeptide consisting of N-(tert-butylcarbamoyl)-3-methyl-L-valyl, a cyclopropyl-fused prolyl and 3-amino-4-cyclobutyl-2-oxobutanamide residues joined in sequence. Used for treatment of chronic hepatitis C virus genotype 1 infection.		2.610tripeptide;
ureas		antiviral drug;
hepatitis C protease inhibitor;
peptidomimetic
vx 702
VX 702: a p38 MAP kinase inhibitor		2.0810phenylpyridine
ly 411575
[no description available]		2.610dibenzoazepine;
difluorobenzene;
lactam;
secondary alcohol		EC 3.4.23.46 (memapsin 2) inhibitor
galidesivir
[no description available]		2.610
volasertib
BI 6727: a polo-like kinase inhibitor with broad antitumor activity; structure in first source		2.0810
PB28
PB28 : A member of the class of tetralins that is tetralin that is substituted by 3-(4-cyclohexylpiperazin-1-yl)propyl and methoxy groups at positions 1 and 5, respectively. It is a sigma 2 (sigma2) receptor agonist (Ki = 0.68 nM) and exhibits antineoplastic and anti SARS-CoV-2 activities.		2.5820aromatic ether;
piperazines;
tetralins		anticoronaviral agent;
antineoplastic agent;
apoptosis inducer;
sigma-2 receptor agonist
azd 7762
[no description available]		2.0810aromatic amide;
thiophenes
krp-203
[no description available]		2.0810
mk 0354
[no description available]		2.0810
regorafenib
[no description available]		2.0810(trifluoromethyl)benzenes;
aromatic ether;
monochlorobenzenes;
monofluorobenzenes;
phenylureas;
pyridinecarboxamide		antineoplastic agent;
hepatotoxic agent;
tyrosine kinase inhibitor
acetic acid 2-[4-methyl-8-(4-morpholinylsulfonyl)-1,3-dioxo-2-pyrrolo[3,4-c]quinolinyl]ethyl ester
[no description available]		2.0810pyrroloquinoline
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)-4-pyrimidinyl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one
[no description available]		2.0810methoxybenzenes;
substituted aniline
degrasyn
degrasyn: a JAK2 kinase inhibitor that induces rapid degradation of c-Myc protein in MM-1 multiple myeloma and other tumor cell lines; structure in first source		2.610
epoxomicin
[no description available]		420morpholines;
tripeptide		proteasome inhibitor
brivanib
[no description available]		2.0810aromatic ether;
diether;
fluoroindole;
pyrrolotriazine;
secondary alcohol		angiogenesis inhibitor;
antineoplastic agent;
apoptosis inducer;
drug metabolite;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor;
fibroblast growth factor receptor antagonist
icg 001
[no description available]		2.0810peptide
bms 477118
[no description available]		2.610adamantanes;
azabicycloalkane;
monocarboxylic acid amide;
nitrile;
tertiary alcohol		EC 3.4.14.5 (dipeptidyl-peptidase IV) inhibitor;
hypoglycemic agent
pha 680632
PHA 680632: Aurora kinase inhibitor with potent antitumoral activity; structure in first source		2.610
tmc 353121
[no description available]		2.610
amd 070
mavorixafor: a derivative of AMD3100; a CXCR4 blocker		2.610aminoquinoline
mp470
[no description available]		2.0810N-arylpiperazine
danoprevir
[no description available]		2.610
bms-626529
[no description available]		2.610
bms-663068
fostemsavir: an HIV-1 attachment inhibitor; structure in first source		2.610
nu 7441
8-dibenzothiophen-4-yl-2-morpholin-4-yl-chromen-4-one: structure in first source		2.0810dibenzothiophenes
at 7519
4-(2,6-dichlorobenzamido)-N-(piperidin-4-yl)-pyrazole-3-carboxamide : A member of the class of pryrazoles that is 4-amino-1H-pyrazole-3-carboxylic acid in which the primary amino group has been acylated by a 2,6-dichlorobenzoyl group and in which the carboxylic acid has been converted into a carboxamide by formal condensation with the primary amino group of 4-aminopiperidine.		2.0810dichlorobenzene;
piperidines;
pyrazoles;
secondary carboxamide		antineoplastic agent;
EC 2.7.11.22 (cyclin-dependent kinase) inhibitor
marizomib
marizomib: a proteasome inhibitor from a marine bacterium Salinospora; structure in first source		5.8380beta-lactone;
gamma-lactam;
organic heterobicyclic compound;
organochlorine compound;
salinosporamide		antineoplastic agent;
proteasome inhibitor
bi 2536
[no description available]		2.0810
amenamevir
ASP2151: a herpesvirus helicase-primase inhibitor, in a guinea pig model of genital herpes; structure in first source		2.610
vx 765
belnacasan: a NSAID		2.610dipeptide
Dihydrotanshinone I
dihydrotanshinone I: extracted from Radix Salviae		2.610abietane diterpenoidanticoronaviral agent
danusertib
[no description available]		2.0810piperazines
alogliptin
alogliptin: structure in first source. alogliptin : A piperidine that is 3-methyl-2,4-dioxo-3,4-dihydropyrimidine carrying additional 2-cyanobenzyl and 3-aminopiperidin-1-yl groups at positions 1 and 2 respectively (the R-enantiomer). Used in the form of its benzoate salt for treatment of type 2 diabetes.		2.610nitrile;
piperidines;
primary amino compound;
pyrimidines		EC 3.4.14.5 (dipeptidyl-peptidase IV) inhibitor;
hypoglycemic agent
N-[4-(2-tert-butylphenyl)sulfonylphenyl]-2,3,4-trihydroxy-5-[(2-propan-2-ylphenyl)methyl]benzamide
[no description available]		2.0810benzamides
N-[5-[[5-[(4-acetyl-1-piperazinyl)-oxomethyl]-4-methoxy-2-methylphenyl]thio]-2-thiazolyl]-4-[(3,3-dimethylbutan-2-ylamino)methyl]benzamide
[no description available]		2.0810benzamides
abt 869
[no description available]		2.0810aromatic amine;
indazoles;
phenylureas		angiogenesis inhibitor;
antineoplastic agent;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor
fr 180204
FR 180204: structure in first source		2.610pyrazoles;
ring assembly
tavaborole
tavaborole: has antifungal activity; structure in first source. tavaborole : A member of the class of benzoxaboroles that is 1,3-dihydro-1-hydroxy-2,1-benzoxaborole substituted at position 5 by a fluoro group. A topical antifungal agent used for the treatment of onychomycosis (fungal infection of the toenails and fingernails).		2.4110benzoxaborole;
organofluorine compound		antifungal agent;
EC 6.1.1.4 (leucine--tRNA ligase) inhibitor;
protein synthesis inhibitor
dorsomorphin
dorsomorphin: an AMPK inhibitor. dorsomorphin : A pyrazolopyrimidine that is pyrazolo[1,5-a]pyrimidine which is substituted at positions 3 and 6 by pyridin-4-yl and p-[2-(piperidin-1-yl)ethoxy]phenyl groups, respectively. It is a potent, selective, reversible, and ATP-competitive inhibitor of AMPK (AMP-activated protein kinase, EC 2.7.11.31) and a selective inhibitor of bone morphogenetic protein (BMP) signaling.		2.0810aromatic ether;
piperidines;
pyrazolopyrimidine;
pyridines		bone morphogenetic protein receptor antagonist;
EC 2.7.11.31 {[hydroxymethylglutaryl-CoA reductase (NADPH)] kinase} inhibitor
ac 261066
[no description available]		2.0810
quisinostat
[no description available]		2.8220indoles
carfilzomib
[no description available]		10.19401epoxide;
morpholines;
tetrapeptide		antineoplastic agent;
proteasome inhibitor
hcv 796
HCV 796: inhibits HCV RdRp; structure in first source		2.610
gw9508
GW9508: structure in first source		2.0810aromatic amine
jnj 26854165
[no description available]		2.0810
resminostat
resminostat: a histone deacetylase inhibitor; structure in first source		2.610
pf 573228
6-(4-(3-(methylsulfonyl)benzylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-3,4-dihydroquinolin-2(1H)-one: structure in first source		2.0810quinolines
gw 2580
5-(3-methoxy-4-((4-methoxybenzyl)oxy)benzyl)pyrimidine-2,4-diamine: a cFMS kinase inhibitor; structure in first source		2.0810
idelalisib
idelalisib: an antineoplastic agent and p110delta inhibitor; structure in first source. idelalisib : A member of the class of quinazolines that is 5-fluoro-3-phenylquinazolin-4-one in which the hydrogen at position 2 is replaced by a (1S)-1-(3H-purin-6-ylamino)propyl group. used for for the treatment of refractory indolent non-Hodgkin's lymphoma and relapsed chronic lymphocytic leukemia.		2.0810aromatic amine;
organofluorine compound;
purines;
quinazolines;
secondary amino compound		antineoplastic agent;
apoptosis inducer;
EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor
crizotinib
Crizotinib: A piperidine and aminopyridine derivative that acts as an inhibitor of RECEPTOR PROTEIN-TYROSINE KINASES, including ANAPLASTIC LYMPHOMA KINASE (ALK) and HEPATOCYTE GROWTH FACTOR RECEPTOR (HGFR; c-Met). It is used in the treatment of NON-SMALL CELL LUNG CANCER.. crizotinib : A 3-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)pyrazol-4-yl]pyridin-2-amine that has R configuration at the chiral centre. The active enantiomer, it acts as a kinase inhibitor and is used for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC)		2.08103-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)pyrazol-4-yl]pyridin-2-amineantineoplastic agent;
biomarker;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor
5-(5,6-dimethoxy-1-benzimidazolyl)-3-[(2-methylsulfonylphenyl)methoxy]-2-thiophenecarbonitrile
[no description available]		2.0810benzimidazoles
4-[2-(2-chloro-4-fluoroanilino)-5-methyl-4-pyrimidinyl]-N-[(1S)-1-(3-chlorophenyl)-2-hydroxyethyl]-1H-pyrrole-2-carboxamide
Vx-11e: ERK1-2 inhibitor		2.0810aromatic amide;
heteroarene
osi 906
[no description available]		2.0810cyclobutanes;
quinolines
ly2109761
[no description available]		2.0810
chir-265
[no description available]		2.0810aromatic ether
motesanib
[no description available]		2.0810pyridinecarboxamide
az-628
AZ-628: a multikinase inhibitor; structure in first source		2.0810benzamides
zk 756326
2-(2-(4-(3-phenoxybenzyl)piperazin-1-yl)ethoxy)ethanol: a CC chemokine receptor CCR8 agonist; structure in first source		2.610aromatic ether
balapiravir
balapiravir: a prodrug of R1479; structure in first source		2.610
trametinib
[no description available]		2.5820acetamides;
aromatic amine;
cyclopropanes;
organofluorine compound;
organoiodine compound;
pyridopyrimidine;
ring assembly		anticoronaviral agent;
antineoplastic agent;
EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor;
geroprotector
pf-562,271
[no description available]		2.0810indoles
deoxyarbutin
4-((tetrahydro-2H-pyran-2-yl)oxy)phenol: has antineoplastic activity; structure in first source		2.610
abexinostat
abexinostat: structure in first source		2.610benzofurans
silvestrol
silvestrol: isolated from the fruit and twig of Aglaia silvestris. silvestrol : An organic heterotricyclic compound that consists of a 2,3,3a,8b-tetrahydro-H-benzo[b]cyclopenta[d]furan framework substituted by hydroxy groups at positions C-1 and C-8b, a methoxycarbonyl group at C-2, a phenyl group at C-3, a 4-methoxyphenyl group at C-3a, a methoxy group at C-8 and a 1,4-dioxan-2-yloxy group at position C-6 which in turn is substituted by a methoxy group at position 3 and a 1,2-dihydroxyethyl group at position 6. Isolated from Aglaia silvestris, it exhibits antineoplastic activity.		2.610dioxanes;
ether;
methyl ester;
organic heterotricyclic compound		antineoplastic agent;
metabolite
narlaprevir
narlaprevir: an antiviral agent that inhibits hepatitis C virus NS3 protease. narlaprevir : An azabicyclohexane that is (1R,5S)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane substituted by [(3S)-1-(cyclopropylamino)-1,2-dioxoheptan-3-yl]aminoacyl and N-({1-[(tert-butylsulfonyl)methyl]cyclohexyl}carbamoyl)-3-methyl-L-valyl groups at positions 2S and 3, respectively. It is a hepatitis C virus (HCV) NS3/4A serine protease inhibitor (Ki = 6 nM) that is used for the treatment of chronic hepatitis C.		2.610azabicyclohexane;
cyclopropanes;
pyrrolidinecarboxamide;
secondary carboxamide;
sulfone;
tertiary carboxamide;
ureas		anticoronaviral agent;
antiviral drug;
EC 3.4.22.69 (SARS coronavirus main proteinase) inhibitor;
hepatitis C protease inhibitor
teneligliptin
[no description available]		2.610amino acid amide
dextrothyroxine
[no description available]		2.610
veliparib
[no description available]		2.5820benzimidazolesEC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor
ku-0060648
[no description available]		2.0810dibenzothiophenes
dactolisib
dactolisib: antineoplastic agent that inhibits both phosphatidylinositol 3-kinase and mTOR. dactolisib : An imidazoquinoline that is 3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]quinoline substituted at position 1 by a 4-(1-cyanoisopropyl)phenyl group and at position 8 by a quinolin-3-yl group. A dual PI3K/mTOR inhibitor used in cancer treatment.		2.0810imidazoquinoline;
nitrile;
quinolines;
ring assembly;
ureas		antineoplastic agent;
EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor;
mTOR inhibitor
palomid 529
[no description available]		2.0810
pf 03491390
[no description available]		2.610
alloin
[no description available]		2.610anthracenes;
C-glycosyl compound;
cyclic ketone;
phenols		laxative;
metabolite
tosedostat
[no description available]		2.0810carboxylic ester;
hydroxamic acid;
secondary carboxamide
rrx-001
RRx-001: has antineoplastic activity; structure in first source		3.5110
mdv 3100
[no description available]		2.5820(trifluoromethyl)benzenes;
benzamides;
imidazolidinone;
monofluorobenzenes;
nitrile;
thiocarbonyl compound		androgen antagonist;
antineoplastic agent
ku 60019
[no description available]		2.0810
gsk 461364
GSK 461364: an antineoplastic agent that inhibits polo-like kinase 1		2.0810(trifluoromethyl)benzenes
n-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide
N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide: a MEK inhibitor; structure in first source		2.0810
nvp-tae684
[no description available]		2.0810piperidines
bms-650032
asunaprevir: an NS3 protease inhibitor against hepatitis C virus		2.610oligopeptide
4-methyl-3-(2-(2-morpholinoethylamino)quinazolin-6-yl)-n-(3-(trifluoromethyl)phenyl)benzamide
4-methyl-3-(2-(2-morpholinoethylamino)quinazolin-6-yl)-N-(3-(trifluoromethyl)phenyl)benzamide: structure in first source		2.0810
gsk 269962a
[no description available]		2.0810
rg 7128
2'-fluoro-2'-methyl-3',5'-diisobutyryldeoxycytidine: inhibits HCV polymerase; structure in first source		2.610
oligonucleotides
[no description available]		3.2110
oritavancin
oritavancin : A semisynthetic glycopeptide used (as its bisphosphate salt) for the treatment of acute bacterial skin and skin structure infections caused or suspected to be caused by susceptible isolates of designated Gram-positive microorganisms including MRSA.		2.610disaccharide derivative;
glycopeptide;
semisynthetic derivative		antibacterial drug;
antimicrobial agent
a-83-01
A-83-01: an ALK-5 inhibitor; structure in first source		2.0810
3-[(1-methyl-3-indolyl)methylidene]-1H-pyrrolo[3,2-b]pyridin-2-one
[no description available]		2.0810indoles
vx-770
ivacaftor: a CFTR potentiator; structure in first source. ivacaftor : An aromatic amide obtained by formal condensation of the carboxy group of 4-oxo-1,4-dihydroquinoline-3-carboxylic acid with the amino group of 5-amino-2,4-di-tert-butylphenol. Used for the treatment of cystic fibrosis.		2.0810aromatic amide;
monocarboxylic acid amide;
phenols;
quinolone		CFTR potentiator;
orphan drug
buparlisib
NVP-BKM120: a pan class I PI3 kinase inhibitor with antineoplastic activity; structure in first source		2.0810aminopyridine;
aminopyrimidine;
morpholines;
organofluorine compound		antineoplastic agent;
EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor
azd 1480
[no description available]		2.0810
pevonedistat
pevonedistat: a potent and selective inhibitor of NAE (NEDD8-activating enzyme). pevonedistat : A pyrrolopyrimidine that is 7H-pyrrolo[2,3-d]pyrimidine which is substituted by a (1S)-2,3-dihydro-1H-inden-1-ylnitrilo group at position 4 and by a (1S,3S,4S)-3-hydroxy-4-[(sulfamoyloxy)methyl]cyclopentyl group at position 7. It is a potent and selective NEDD8-activating enzyme inhibitor with an IC50 of 4.7 nM, and currently under clinical investigation for the treatment of acute myeloid leukemia (AML) and myelodysplastic syndromes.		4.3230cyclopentanols;
indanes;
pyrrolopyrimidine;
secondary amino compound;
sulfamidate		antineoplastic agent;
apoptosis inducer
fedratinib
fedratinib: a selective small-molecule inhibitor of JAK2		2.0810sulfonamide
gsk690693
[no description available]		2.08101,2,5-oxadiazole;
acetylenic compound;
aromatic amine;
aromatic ether;
imidazopyridine;
piperidines;
primary amino compound;
tertiary alcohol		antineoplastic agent;
EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor
cnf 2024
[no description available]		2.08102-aminopurines;
aromatic ether;
organochlorine compound;
pyridines		antineoplastic agent;
Hsp90 inhibitor
ku 0063794
Ku 0063794: an mTOR inhibitor; structure in first source		2.0810benzyl alcohols;
monomethoxybenzene;
morpholines;
pyridopyrimidine;
tertiary amino compound		antineoplastic agent;
mTOR inhibitor
uk 453,061
UK 453,061: a reverse transcriptase inhibitor/anti-HIV agent; structure in first source		2.610aromatic ether
azd 7545
AZD 7545: an anilide tertiary carbinol; a pyruvate dehydrogenase kinase 2 inhibitor. AZD7545 : A sulfone that is benzene substituted by [4-(dimethylcarbamoyl)phenyl]sulfonyl, chloro and [(2R)-3,3,3-trifluoro-2-hydroxy-2-methylpropanoyl]amino groups at positions 1, 3 and 4, respectively. It is a potent and non-ATP-competitive inhibitor of pyruvate dehydrogenase kinase 2 (PDHK2) with IC50 of 6.4 nM and exhibits glucose-lowering activity. Also inhibits PDHK1 at higher levels (IC50 = 36.8 nM).		2.0810benzamides;
monochlorobenzenes;
organofluorine compound;
secondary carboxamide;
sulfone;
tertiary alcohol;
tertiary carboxamide		EC 2.7.11.2 - [pyruvate dehydrogenase (acetyl-transferring)] kinase inhibitor;
hypoglycemic agent
nutlin-3b
[no description available]		2.0810Nutlin;
piperazinone		anticoronaviral agent
N-(2-aminophenyl)-2-pyrazinecarboxamide
[no description available]		2.610aromatic amide
pf 04217903
[no description available]		2.0810quinolines
gdc 0941
pictrelisib : A sulfonamide composed of indazole, morpholine, and methylsulfonyl-substituted piperazine rings bound to a thienopyrimidine ring.		2.0810indazoles;
morpholines;
piperazines;
sulfonamide;
thienopyrimidine		EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor
sm 164
SM 164: a bivalent Smac mimetic with antineoplastic activity; structure in first source		2.0810benzenes;
organic heterobicyclic compound;
secondary carboxamide;
triazoles		antineoplastic agent;
apoptosis inducer;
radiosensitizing agent
ph 797804
PH 797804: an NSAID; structure in first source. PH 797804 : A member of the class of benzamides obtained by formal condensation of the carboxy group of 3-{3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1-yl}-4-methylbenzoic acid with the amino group of methylamine.		2.0810aromatic ether;
benzamides;
organobromine compound;
organofluorine compound;
pyridone		anti-inflammatory agent;
EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor
pha 408
PHA 408: an IKK-2 antagonist; structure in first source		2.0810
gsk 1016790a
GSK1016790A : A tertiary carboxamide that is piperazine in which one of the amino groups has undergone condensation with the carboxy group of N-[(2,4-dichlorophenyl)sulfonyl]-L-serine, while the other has undergone condensation with the carboxy group of N-(1-benzothiophen-2-ylcarbonyl)-L-leucine. It is a cell-permeable, potent and selective agonist of the TRPV4 (transient receptor potential vanilloid 4) channel.		2.08101-benzothiophenes;
aromatic primary alcohol;
dichlorobenzene;
N-acylpiperazine;
sulfonamide;
tertiary carboxamide		TRPV4 agonist
tegobuvir
tegobuvir: a non-structural protein 5B polymerase inhibitor		2.610
pf-429242
PF-429242: a subtilisin kexin isozyme-1/site-1 protease inhibitor		2.610
olaparib
[no description available]		2.5820cyclopropanes;
monofluorobenzenes;
N-acylpiperazine;
phthalazines		antineoplastic agent;
apoptosis inducer;
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor
srt1720
[no description available]		2.0810
plx 4720
PLX 4720: a B-Raf(V600E) kinase inhibitor; structure in first source		2.0810aromatic ketone;
difluorobenzene;
organochlorine compound;
pyrrolopyridine;
sulfonamide		antineoplastic agent;
B-Raf inhibitor
cx 4945
[no description available]		2.5820
pci 34051
PCI 34051: an HDAC8 inhibitor		2.610indolecarboxamide
cudc 101
7-(4-(3-ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)-N-hydroxyheptanamide: a histone deacetylase inhibitor; structure in first source		2.0810
mln 8237
MLN 8237: an aurora kinase A inhibitor		2.520benzazepine
lde225
sonidegib: specific Smoothened/Smo antagonist. sonidegib : A member of the classo of biphenyls that is the amide obtained by formal condensation of the carboxy group of 2-methyl-4'-(trifluoromethoxy)[1,1'-biphenyl]-3-carboxylic acid with the amino group of 6-(2,6-dimethylmorpholin-4-yl)pyridin-3-amine. Used (as its phosphate salt) for treatment of locally advanced basal cell carcinoma.		2.0810aminopyridine;
aromatic ether;
benzamides;
biphenyls;
morpholines;
organofluorine compound;
tertiary amino compound		antineoplastic agent;
Hedgehog signaling pathway inhibitor;
SMO receptor antagonist
gdc 0449
HhAntag691: inhibits the hedgehog pathway and ABC transporters; has antineoplastic activity		2.0810benzamides;
monochlorobenzenes;
pyridines;
sulfone		antineoplastic agent;
Hedgehog signaling pathway inhibitor;
SMO receptor antagonist;
teratogenic agent
sgx 523
[no description available]		2.0810aryl sulfide;
biaryl;
pyrazoles;
quinolines;
triazolopyridazine		c-Met tyrosine kinase inhibitor;
nephrotoxic agent
bms 777607
N-(4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide: a Met kinase inhibitor; structure in first source		2.0810aromatic amide
sgi 1776
SGI 1776: a Pim kinase inhibitor; structure in first source		2.4820imidazoles
lomibuvir
lomibuvir: an antiviral agent with polymerase NS5 inhibitory activity		2.610thiophenecarboxylic acid
delanzomib
[no description available]		5.3690C-terminal boronic acid peptide;
phenylpyridine;
secondary alcohol;
threonine derivative		antineoplastic agent;
apoptosis inducer;
proteasome inhibitor
pci 32765
ibrutinib: a Btk protein inhibitor. ibrutinib : A member of the class of acrylamides that is (3R)-3-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine in which the piperidine nitrogen is replaced by an acryloyl group. A selective and covalent inhibitor of the enzyme Bruton's tyrosine kinase, it is used for treatment of B-cell malignancies.		2.0810acrylamides;
aromatic amine;
aromatic ether;
N-acylpiperidine;
pyrazolopyrimidine;
tertiary carboxamide		antineoplastic agent;
EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor
ponatinib
[no description available]		2.0810(trifluoromethyl)benzenes;
acetylenic compound;
benzamides;
imidazopyridazine;
N-methylpiperazine		antineoplastic agent;
tyrosine kinase inhibitor
pitavastatin(1-)
pitavastatin(1-) : A hydroxy monocarboxylic acid anion that is the conjugate base of pitavastatin, obtained by deprotonation of the carboxy group.		2.610hydroxy monocarboxylic acid anion
amg 900
N-(4-((3-(2-amino-4-pyrimidinyl)-2-pyridinyl)oxy)phenyl)-4-(4-methyl-2-thienyl)-1-phthalazinamine: a pan-aurora kinase inhibitor; structure in first source		2.0810
mk-1775
adavosertib: a Wee1 kinase inhibitor; structure in first source		3.6620piperazines
bag956
BAG956: an imidazo[4,5-c]quinoline; dual PI3K/PDK-1 inhibitor, used in antileukemic therapies		2.0810
quizartinib
[no description available]		2.0810benzoimidazothiazole;
isoxazoles;
morpholines;
phenylureas		antineoplastic agent;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor;
necroptosis inhibitor
GRL-0617
GRL-0617 : A benzamide resulting from the formal condensation of the carboxy group of 5-amino-2-methylbenzoic acid with the amino group of (1R)-1-(naphthalen-1-yl)ethan-1-amine. It is a potent noncovalent inhibitor (IC50 = 600 nM) of severe acute respiratory syndrome-coronavirus papain-like protease (SARS-CoV PLpro).		2.610benzamides;
naphthalenes;
secondary carboxamide;
substituted aniline		anticoronaviral agent;
protease inhibitor
N-[4-[3-[[[7-(hydroxyamino)-7-oxoheptyl]amino]-oxomethyl]-5-isoxazolyl]phenyl]carbamic acid tert-butyl ester
CAY10603: a HDAC6 inhibitor		2.5820carbamate ester
niraparib
niraparib: structure in first source. niraparib : A 2-[4-(piperidin-3-yl)phenyl]-2H-indazole-7-carboxamide that has S-configuration. It is a potent inhibitor of PARP1 and PARP2 (IC50 of 3.8 and 2.1 nM, respectively) and approved as a first-line maintenance treatment for women with advanced ovarian cancer after responding to platinum-based chemotherapy.		2.6102-[4-(piperidin-3-yl)phenyl]-2H-indazole-7-carboxamideantineoplastic agent;
apoptosis inducer;
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor;
radiosensitizing agent
tak 733
[no description available]		2.0810
mk 2206
MK 2206: a protein kinase inhibitor and antineoplastic agent		2.5520organic heterotricyclic compoundEC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor
navitoclax
[no description available]		2.830aryl sulfide;
monochlorobenzenes;
morpholines;
N-sulfonylcarboxamide;
organofluorine compound;
piperazines;
secondary amino compound;
sulfone;
tertiary amino compound		antineoplastic agent;
apoptosis inducer;
B-cell lymphoma 2 inhibitor
sns 314
SNS 314: an aurora kinase inhibitor; structure in first source		2.0810ureas
jzl 184
JZL 184: inhibits monoacylglycerol lipase; structure in first source		2.5820benzodioxoles
gsk 650394
[no description available]		2.610phenylpyridine
n-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide
N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide: a Janus kinase 1 and Janus kinase 2 inhibitor; structure in first source. momelotinib : A benzamide obtained by formal condensation of the carboxy group of 4-{2-[4-(morpholin-4-yl)anilino]pyrimidin-4-yl}benzoic acid with the primary amino group of aminoacetonitrile. It is an ATP-competitive JAK1/JAK2 inhibitor with IC50 of 11 nM and 18 nM, respectively. Used for the treatment of patients with intermediate- or high-risk myelofibrosis.		2.0810aminopyrimidine;
benzamides;
morpholines;
nitrile;
secondary amino compound;
tertiary amino compound		anti-anaemic agent;
antineoplastic agent;
apoptosis inducer;
EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor
dcc-2036
rebastinib: an inhibitor of Tie2 tyrosine kinase receptor and antineoplastic agent		2.0810organofluorine compound;
phenylureas;
pyrazoles;
pyridinecarboxamide;
quinolines		tyrosine kinase inhibitor
oprozomib
ONX 0912: antineoplastic; an orally active proteasome inhibitor; structure in first source		6.13110
az 960
[no description available]		2.610
cabozantinib
cabozantinib: a multikinase inhibitor. cabozantinib : A dicarboxylic acid diamide that is N-phenyl-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide in which the hydrogen at position 4 on the phenyl ring is substituted by a (6,7-dimethoxyquinolin-4-yl)oxy group. A multi-tyrosine kinase inhibitor, used (as its malate salt) for the treatment of progressive, metastatic, medullary thyroid cancer.		2.0810aromatic ether;
dicarboxylic acid diamide;
organofluorine compound;
quinolines		antineoplastic agent;
tyrosine kinase inhibitor
golgicide a
golgicide A: inhibits the cis-golgi ArfGEF GBF1; structure in first source. golgicide A : A diastereoisomeric mixture comprising racemic cis- and racemic trans-goglioside A in a 10:1 ratio. It is a potent and rapidly reversible GBF1 (Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1) inhibitor. The (3aS,4R,9bR) isomer is the most active (see Bioorg. Med. Chem. Lett., 2012, 22, 5177-5181).		2.610diastereoisomeric mixturecis-Golgi ArfGEF GBF inhibitor
N-(2,6-difluorophenyl)-5-[3-[2-[5-ethyl-2-methoxy-4-[4-(4-methylsulfonyl-1-piperazinyl)-1-piperidinyl]anilino]-4-pyrimidinyl]-2-imidazo[1,2-a]pyridinyl]-2-methoxybenzamide
[no description available]		2.0810benzamides
incb-018424
[no description available]		2.0810nitrile;
pyrazoles;
pyrrolopyrimidine		antineoplastic agent;
EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor
bix 01294
[no description available]		2.0810piperidines
cobicistat
[no description available]		2.6101,3-thiazoles;
carbamate ester;
monocarboxylic acid amide;
morpholines;
ureas		P450 inhibitor
bms-790052
daclatasvir: an HCV NS5A inhibitor. daclatasvir : A member of the class of biphenyls that is a potent inhibitor of nonstructural protein 5A and is used (as its hydrochloride salt) for treatment of hepatitis C.		2.610biphenyls;
carbamate ester;
carboxamide;
imidazoles;
valine derivative		antiviral drug;
nonstructural protein 5A inhibitor
pf 3845
PF 3845: inhibits fatty acid amide hydrolase		2.0810piperidines
gsk 2126458
omipalisib: inhibitor of mTOR protein. omipalisib : A member of the class of quinolines that is quinoline which is substituted by pyridazin-4-yl and 5-[(2,4-difluorobenzene-1-sulfonyl)amino]-6-methoxypyridin-3-yl groups at positions 4 and 6, respectively. It is a highly potent inhibitor of PI3K and mTOR developed by GlaxoSmithKline and was previously in human phase 1 clinical trials for the treatment of idiopathic pulmonary fibrosis and solid tumors.		2.5520aromatic ether;
difluorobenzene;
pyridazines;
pyridines;
quinolines;
sulfonamide		anticoronaviral agent;
antineoplastic agent;
autophagy inducer;
EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor;
mTOR inhibitor;
radiosensitizing agent
ldn 193189
LDN 193189: inhibits bone morphogenetic protein signaling		2.0810pyrimidines
ucph 101
2-amino-4-(4-methoxyphenyl)-7-(naphthalen-1-yl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile: structure in first source		2.610
plx4032
[no description available]		2.0810aromatic ketone;
difluorobenzene;
monochlorobenzenes;
pyrrolopyridine;
sulfonamide		antineoplastic agent;
B-Raf inhibitor
(2S)-2-[[2-(2,3-dihydro-1H-inden-5-yloxy)-9-[(4-phenylphenyl)methyl]-6-purinyl]amino]-3-phenyl-1-propanol
[no description available]		2.0810biphenyls
gsk 1363089
GSK 1363089: a multikinase inhibitor that acts on Met, RON, Axl, and VEGFR; structure in first source		2.0810aromatic ether
kin-193
[no description available]		2.0810pyridopyrimidine
5-(3-methylsulfonylphenyl)-4-[(1-methyl-5-tetrazolyl)thio]thieno[2,3-d]pyrimidine
[no description available]		2.610aryl sulfide;
thienopyrimidine
bay 869766
[no description available]		2.0810
baricitinib
[no description available]		2.610azetidines;
nitrile;
pyrazoles;
pyrrolopyrimidine;
sulfonamide		anti-inflammatory agent;
antirheumatic drug;
antiviral agent;
EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor;
immunosuppressive agent
4-[6-[4-(methoxycarbonylamino)phenyl]-4-(4-morpholinyl)-1-pyrazolo[3,4-d]pyrimidinyl]-1-piperidinecarboxylic acid methyl ester
WYE-354: an mTOR inhibitor; structure in first source		2.0810carbamate ester
arry 520
filanesib: a kinesin spindle protein inhibitor		4.2420
KOM70144
KOM70144 : A benzamide that is GRL-0617 in which one of the hydrogen's of the primary amino group is replaced by an acetyl group. It an inhibitor of SARS-CoV and SARS-CoV-2 papain-like protease (PLpro) with an IC50 of 2.6 muM and 5.0 muM, respectively. It also inhibits SARS-CoV and SARS-CoV-2 infection of Vero E6 cells in vitro (EC50 values are 13.1 and 21 muM, respectively).		2.610acetamides;
benzamides;
naphthalenes;
secondary carboxamide		anticoronaviral agent;
protease inhibitor
piperidines
Piperidines: A family of hexahydropyridines.		2.3110
6-[(3-aminophenyl)methyl]-4-methyl-2-methylsulfinyl-5-thieno[3,4]pyrrolo[1,3-d]pyridazinone
ML-265: a small molecule activator of PKM2		2.0810organic heterobicyclic compound;
organonitrogen heterocyclic compound;
organosulfur heterocyclic compound
e-52862
[no description available]		2.610
ly2811376
[no description available]		2.610
anagliptin
anagliptin: anagliptin hydrochloride salt is the active compound		2.610amino acid amide
3-[[4-(2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl)-1,4-diazepan-1-yl]sulfonyl]aniline
[no description available]		2.0810benzenes;
sulfonamide
cp 466722
[no description available]		2.0810quinazolines
an2728
crisaborole: NSAID, Dermatologic Agent; structure in first source. crisaborole : A member of the class of benzoxaboroles that is 5-hydroxy-1,3-dihydro-2,1-benzoxaborole in which the phenolic hydrogen has been replaced by a 4-cyanophenyl group. A phosphodiesterase 4 inhibitor that is used for treatment of mild to moderate atopic dermatitis in children and adults.		2.4110aromatic ether;
benzoxaborole;
nitrile		antipsoriatic;
non-steroidal anti-inflammatory drug;
phosphodiesterase IV inhibitor
gardiquimod
[no description available]		2.610
CAY10626
[no description available]		2.0810ureas
grazoprevir
grazoprevir: has antiviral activity; component of Zepatier. grazoprevir : An azamacrocyclic compound that is a hepatitis C protease inhibitor used in combination with elbasvir (under the brand name Zepatier) for treatment of chronic HCV genotypes 1 or 4 infection in adults.		2.610aromatic ether;
azamacrocycle;
carbamate ester;
cyclopropanes;
lactam;
N-sulfonylcarboxamide;
quinoxaline derivative		antiviral drug;
hepatitis C protease inhibitor;
hepatoprotective agent
thiopental sodium
[no description available]		2.0810organochlorine compound;
piperazines;
pyrimidines		antineoplastic agent;
tyrosine kinase inhibitor
abt-450
paritaprevir: inhibits HCV NS3 protease. paritaprevir : An azamacrocycle which is used which is in combination with dasabuvir sodium hydrate, ombitasvir and ritonavir (under the trade name Viekira Pak) for treatment of chronic hepatitis C virus genotype 1 infection as well as cirrhosis of the liver.		2.610
letermovir
letermovir: has antiviral activity; structure in first source		2.610
sofosbuvir
Sofosbuvir: A uridine monophosphate analog inhibitor of HEPATITIS C VIRUS (HCV) polymerase NS5B that is used as an ANTIVIRAL AGENT in the treatment of CHRONIC HEPATITIS C.. sofosbuvir : A nucleotide conjugate that is used in combination with ledipasvir (under the trade name Harvoni) for the treatment of chronic hepatitis C genotype 1 infection.		2.610isopropyl ester;
L-alanyl ester;
nucleotide conjugate;
organofluorine compound;
phosphoramidate ester		antiviral drug;
hepatitis C protease inhibitor;
prodrug
5-(4-amino-1-propan-2-yl-3-pyrazolo[3,4-d]pyrimidinyl)-1,3-benzoxazol-2-amine
sapanisertib: an mTOR inhibitor		2.610benzoxazole
blz 945
[no description available]		2.610
pha 793887
[no description available]		2.0810piperidinecarboxamide
azd3839
AZD3839: a BACE1 inhibitor; structure in first source		2.610
pf 3084014
nirogacestat: an antineoplastic agent. nirogacestat : A member of the class of imidazoles that is 1H-imidazole substituted by a 1-[(2,2-dimethylpropyl)amino]-2-methylpropan-2-yl group at position 1 and a {N-[(2S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl]-L-norvalyl}amino group at position 4. It is a gamma-secretase inhibitor whose hydrobromide salt is indicated for adult patients with progressing desmoid tumours who require systemic treatment.		2.610
unc 0638
UNC 0638: inhibits lysine methyltransferases G9a and GLP; structure in first source		2.610quinazolines
gs-9620
[no description available]		2.610
nvp-bsk805
[no description available]		2.0810
xmd 8-92
XMD8-92 : A dimethylpyrimido[4,5-b][1,4]benzodiazepin-6-one carrying at C-2 on the pyrimidine ring a [2-ethoxy-4-(4-hydroxypiperidin-1-yl)phenyl]amino substituent. It is an inhibitor of the BMK1 kinase pathway.		2.0810pyrimidobenzodiazepineprotein kinase inhibitor
n-((5-(methanesulfonyl)pyridin-2-yl)methyl)-6-methyl-5-(1-methyl-1h-pyrazol-5-yl)-2-oxo-1-(3-(trifluoromethyl)phenyl)-1,2-dihydropyridine-3-carboxamide
N-((5-(methanesulfonyl)pyridin-2-yl)methyl)-6-methyl-5-(1-methyl-1H-pyrazol-5-yl)-2-oxo-1-(3-(trifluoromethyl)phenyl)-1,2-dihydropyridine-3-carboxamide: structure in first source		2.610
bms 708163
BMS 708163: structure in first source		2.610oxadiazole;
ring assembly
jq1 compound
[no description available]		2.5820carboxylic ester;
organochlorine compound;
tert-butyl ester;
thienotriazolodiazepine		angiogenesis inhibitor;
anti-inflammatory agent;
antineoplastic agent;
apoptosis inducer;
bromodomain-containing protein 4 inhibitor;
cardioprotective agent;
ferroptosis inducer
jnj38877605
[no description available]		2.0810quinolines
N-[3-(1,3-benzothiazol-2-yl)-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl]acetamide
[no description available]		2.0810benzothiazoles
dinaciclib
[no description available]		2.1310pyrazolopyrimidine
1-(5-((2,4-difluorophenyl)thio)-4-nitrothiophen-2-yl)ethanone
1-(5-((2,4-difluorophenyl)thio)-4-nitrothiophen-2-yl)ethanone: a USP7 inhibitor; structure in first source		2.610
gsk525762a
molibresib: mimicks acetylated histones; structure in first source		2.610benzodiazepine
ML240
ML240 : A member of the class of quinazolines that is quinazoline which is substituted at positions 2, 5 and 8 by 2-amino-1H-benzimidazol-1-yl, benzylnitrilo and methoxy groups, respectively. It is a ATP-competetive inhibitor of AAA ATPase p97, also known as valosin-containing protein (VCP).		2.610aromatic amine;
aromatic ether;
benzimidazoles;
primary amino compound;
quinazolines;
secondary amino compound		antineoplastic agent
birinapant
birinapant: a Smac mimetic with antineoplastic activity		2.610dipeptide
torin 1
torin 1 : A member of the class of pyridoquinolines that is 9-(quinolin-3-yl)benzo[h][1,6]naphthyridin-2-one bearing an additional 4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl substituent at position 1. It is a potent inhibitor of mTOR and exhibits anti-cancer properties.		2.0810N-acylpiperazine;
N-arylpiperazine;
organofluorine compound;
pyridoquinoline;
quinolines		antineoplastic agent;
mTOR inhibitor
ly2886721
[no description available]		2.610
nms-p118
NMS-P118: a PARP-1 inhibitor; structure in first source		2.610
abt-199
venetoclax: A BCL-2 inhibitor with antineoplastic activity that is used in the treatment of CHRONIC LYMPHOCYTIC LEUKEMIA associated with chromosome 17p deletion; structure in first source.. venetoclax : A member of the class of pyrrolopyridines that is a potent inhibitor of the antiapoptotic protein B-cell lymphoma 2. It is used for treamtment of chronic lymphocytic leukemia with 17p deletion.		3.7820aromatic ether;
C-nitro compound;
monochlorobenzenes;
N-alkylpiperazine;
N-arylpiperazine;
N-sulfonylcarboxamide;
oxanes;
pyrrolopyridine		antineoplastic agent;
apoptosis inducer;
B-cell lymphoma 2 inhibitor
ly2940680
[no description available]		2.0810
tubastatin a
[no description available]		2.610hydroxamic acid;
pyridoindole;
tertiary amino compound		EC 3.5.1.98 (histone deacetylase) inhibitor
1-[4-fluoro-3-(trifluoromethyl)phenyl]-3-(5-pyridin-4-yl-1,3,4-thiadiazol-2-yl)urea
[no description available]		2.0810ureas
pracinostat
pracinostat : A hydroxamic acid that is N-hydroxyacrylamide which is substituted at position 3 by a 2-butyl-1-[2-(diethylamino)ethyl]-1H-benzimidazol-5-yl group (the E isomer). An orally available pan-histone deacetylase inhibitor with demonstrated activity in the treatment of advanced solid tumours.		2.610benzimidazole;
hydroxamic acid;
olefinic compound;
tertiary amino compound		antimalarial;
antineoplastic agent;
apoptosis inducer;
EC 3.5.1.98 (histone deacetylase) inhibitor
ro 4929097
[no description available]		2.0810dibenzoazepine;
dicarboxylic acid diamide;
lactam;
organofluorine compound		EC 3.4.23.46 (memapsin 2) inhibitor
mln 9708
[no description available]		2.6120
gsk4112
GSK4112: a Rev-erbalpha agonist; structure in first source		2.0810
spautin-1
[no description available]		2.610
torin 2
torin 2 : A member of the class of pyridoquinolines that is benzo[h][1,6]naphthyridin-2-one carrying additional 3-(trifluoromethyl)phenyl and 6-aminopyridin-3-yl substituents at positions 1 and 9 respectively. It is a potent inhibitor of mTOR and exhibits anti-cancer properties.		2.0810aminopyridine;
organofluorine compound;
primary amino compound;
pyridoquinoline		antineoplastic agent;
mTOR inhibitor
pf-4708671
[no description available]		2.0810
ldn 57444
LDN 57444: inhibitor of ubiquitin C-terminal hydrolase-L1; structure in first source		2.610
gsk1210151a
GSK1210151A: inhibitor of the BET family of proteins; structure in first source		2.610imidazoquinoline
i-bet726
[no description available]		2.610
acy-1215
ricolinostat: an HDAC6 inhibitor; structure in first source		420pyrimidinecarboxylic acid
N-[4-(1-benzoyl-4-piperidinyl)butyl]-3-(3-pyridinyl)-2-propenamide
[no description available]		2.0810benzamides;
N-acylpiperidine
2-methoxy-N-[3-[4-[3-methyl-4-[(6-methyl-3-pyridinyl)oxy]anilino]-6-quinazolinyl]prop-2-enyl]acetamide
2-methoxy-N-[3-[4-[3-methyl-4-[(6-methyl-3-pyridinyl)oxy]anilino]-6-quinazolinyl]prop-2-enyl]acetamide : A member of the class of quinazolines that is quinazoline substituted by {3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino and 3-(2-methoxyacetamido)prop-1-en-1-yl groups at positions 4 and 6, respectively.		2.0810aromatic ether;
methylpyridines;
olefinic compound;
quinazolines;
secondary amino compound;
secondary carboxamide;
toluenes
belinostat
[no description available]		2.0810olefinic compound
cudc-907
[no description available]		2.610
mobic
Meloxicam: A benzothiazine and thiazole derivative that acts as a NSAID and cyclooxygenase-2 (COX-2) inhibitor. It is used in the treatment of RHEUMATOID ARTHRITIS; OSTEOARTHRITIS; and ANKYLOSING SPONDYLITIS.. meloxicam : A benzothiazine that is piroxicam in which the pyridin-2-yl group is replaced by a 5-methyl-1,3-thiazol-2-yl group. A non-steroidal anti-inflammatory drug and selective inhibitor of COX-2, it is used particularly for the management of rheumatoid arthritis.		2.6101,3-thiazoles;
benzothiazine;
monocarboxylic acid amide		analgesic;
antirheumatic drug;
cyclooxygenase 2 inhibitor;
non-steroidal anti-inflammatory drug
laquinimod
[no description available]		3.2110aromatic amide
ethyl 1-benzyl-3-hydroxy-2(5h)-oxopyrrole-4-carboxylate
ethyl 1-benzyl-3-hydroxy-2(5H)-oxopyrrole-4-carboxylate: RN & structure given in first source		2.0810carboxylic acid;
pyrroline
tipranavir
tipranavir: inhibits HIV-1 protease. tipranavir : A pyridine-2-sulfonamide substituted at C-5 by a trifluoromethyl group and at the sulfonamide nitrogen by a dihydropyrone-containing m-tolyl substituent. It is an HIV-1 protease inhibitor.		2.610sulfonamideantiviral drug;
HIV protease inhibitor
tasquinimod
tasquinimod: a lead second generation quinoline-3-carboxamide anti-angiogenic agent for the treatment of prostate cancer; structure in first source		2.610
a 769662
[no description available]		2.0810biphenyls
gsk1265744
[no description available]		2.610difluorobenzene;
monocarboxylic acid amide;
organic heterotricyclic compound;
secondary carboxamide		HIV-1 integrase inhibitor
abt-267
ombitasvir: inhibits HCV NS5A protein, component of Viekirax. ombitasvir : A dipeptide derivative which is used which is in combination with dasabuvir sodium hydrate, paritaprevir and ritonavir (under the trade name Viekira Pak) for treatment of chronic hepatitis C virus genotype 1 infection as well as cirrhosis of the liver.		2.610aromatic amide;
carbamate ester;
dipeptide;
pyrrolidines		antiviral drug;
hepatitis C virus nonstructural protein 5A inhibitor
abt-333
dasabuvir: an antiviral agent. dasabuvir : A member of the class of pyrimidone, which is (as the monohydrate of its sodium salt) in combination with ombitasvir, paritaprevir and ritonavir (under the trade name Viekira Pak) for treatment of chronic hepatitis C virus genotype 1 infection as well as cirrhosis of the liver.		2.610aromatic ether;
naphthalenes;
pyrimidone;
sulfonamide		antiviral drug;
nonnucleoside hepatitis C virus polymerase inhibitor
byl719
[no description available]		2.2110proline derivative
rpx7009
RPX7009: a beta-lactamase inhibitor; structure in first source		2.4110
rgfp966
[no description available]		2.610
rg2833
RG2833: a histone deacetylase inhibitor; structure in first source		2.610
pi-1840
PI-1840: has both antineoplastic and proteasome inhibitory activities; structure in first source		2.610
LimKi 3
LIMKi3: LIMK inhibitor. LimKi 3 : A member of the class of pyrazoles that is 1-(2,6-dichlorophenyl)-1H-pyrazole which is substituted by a difluoromethyl group at position 3 and by a 2-(isobutyrylamino)-1,3-thiazol-5-yl group at position 5. It is a a potent cell-permeable inhibitor of LIM kinase 1 and 2.		2.08101,3-thiazoles;
dichlorobenzene;
organofluorine compound;
pyrazoles;
secondary carboxamide		LIM kinase inhibitor
1-[4-amino-7-[3-(2-methoxyethylamino)propyl]-5-(4-methylphenyl)-6-pyrrolo[2,3-d]pyrimidinyl]-2-fluoroethanone
[no description available]		2.0810pyrroles
2-[5-[(3,5-dimethyl-1H-pyrrol-2-yl)methylidene]-4-methoxy-2-pyrrolylidene]indole
[no description available]		2.0810dipyrrins
acy-738
[no description available]		2.610
pelabresib
CPI-0610: a bromodomain and extra-terminal protein inhibitor with antineoplastic activity; structure in first source		2.610monochlorobenzenes;
organic heterotricyclic compound;
primary carboxamide		antineoplastic agent;
bromodomain-containing protein 4 inhibitor
N-hydroxy-3-[4-[[2-(2-methyl-1H-indol-3-yl)ethylamino]methyl]phenyl]-2-propenamide
[no description available]		2.0810tryptamines
3-[(5-tert-butyl-1H-imidazol-4-yl)methylidene]-6-(phenylmethylene)piperazine-2,5-dione
[no description available]		2.0810pyrazines
gsk837149a
GSK837149A: structure in first source		2.0810
N-[4-(3-chloro-4-fluoroanilino)-7-[[(3S)-3-oxolanyl]oxy]-6-quinazolinyl]-4-(dimethylamino)-2-butenamide
[no description available]		2.0810quinazolines
N-[4-(3-chloro-4-fluoroanilino)-7-methoxy-6-quinazolinyl]-4-(1-piperidinyl)-2-butenamide
[no description available]		2.0810quinazolines
wnt-c59
2-(4-(2-methylpyridin-4-yl)phenyl)-N-(4-(pyridin-3-yl)phenyl)acetamide: a PORCN acyltransferase inhibitor; structure in first source		2.0810
5-[1-(2-hydroxyethyl)-3-pyridin-4-yl-4-pyrazolyl]-2,3-dihydroinden-1-one oxime
[no description available]		2.0810indanes
gs-5806
presatovir: a respiratory syncytial virus entry inhibitor		2.610
doravirine
[no description available]		2.610
gn6958
GN6958: inhibits SUMO-sentrin specific protease 1 (SENP1); structure in first source		2.610
vx-787
pimodivir: non‐nucleotide inhibitor of the polymerase basic protein 2 (PB2) subunit of the influenza A that is active against H1N1, H7N9 and H5N1, as well as influenza A strains with reduced susceptibility to NAIs		2.610
ledipasvir
ledipasvir : A benzimidazole derivative that is used in combination with sofosbuvir (under the trade name Harvoni) for the treatment of chronic hepatitis C genotype 1 infection.		2.610azaspiro compound;
benzimidazole;
bridged compound;
carbamate ester;
carboxamide;
fluorenes;
imidazoles;
L-valine derivative;
N-acylpyrrolidine;
organofluorine compound		antiviral drug;
hepatitis C protease inhibitor
gs-5816
velpatasvir: an NS5A inhibitor used for treating hepatitis C infections. velpatasvir : A complex organic heteropentacyclic compound that is a hepatitis C virus nonstructural protein 5A inhibitor used in combination with sofosbuvir (under the brand name Epclusa) for treatment of patients with chronic hepatitis C of all six major genotypes.		2.610carbamate ester;
ether;
imidazoles;
L-valine derivative;
N-acylpyrrolidine;
organic heteropentacyclic compound;
ring assembly		antiviral drug;
hepatitis C virus nonstructural protein 5A inhibitor
g007-lk
G007-LK: potent and specific small-molecule tankyrase inhibitor; structure in first source		2.610
4-((1-butyl-3-phenylureido)methyl)-n-hydroxybenzamide
4-((1-butyl-3-phenylureido)methyl)-N-hydroxybenzamide: inhibits HDAC6; structure in first source		2.610
selinexor
selinexor: inhibits karyopherin XPO1		11.1941
verdinexor
verdinexor: a selective inhibitor of nuclear export		2.610
cb-839
[no description available]		2.6920
mk-8742
elbasvir: inhibits NS5A protein of hepatitis C virus. elbasvir : A complex organic heterotetracyclic compound that is a hepatitis C virus nonstructural protein 5A inhibitor used in combination with grazoprevir (under the brand name Zepatier) for treatment of chronic HCV genotypes 1 or 4 infection in adults.		2.610carbamate ester;
imidazoles;
L-valine derivative;
N-acylpyrrolidine;
organic heterotetracyclic compound;
ring assembly		antiviral drug;
hepatitis C virus nonstructural protein 5A inhibitor;
hepatoprotective agent
atglistatin
atglistatin: inhibits adipose triglyceride lipase; structure in first source. atglistatin : A biphenyl that is 1,1'-biphenyl substituted by (dimethylcarbamoyl)amino and dimethylamino groups at positions 3 and 4', respectively. It is a potent inhibitor of adipose triglyceride lipase activity (IC50 = 700nM).		2.610
xen445
[no description available]		2.610
santacruzamate a
santacruzamate A: HDAC2 inhibitor from the Panamanian marine cyanobacterium cf. Symploca sp.; structure in first source		2.610organonitrogen compound;
organooxygen compound
cyclin d1
Cyclin D1: Protein encoded by the bcl-1 gene which plays a critical role in regulating the cell cycle. Overexpression of cyclin D1 is the result of bcl-1 rearrangement, a t(11;14) translocation, and is implicated in various neoplasms.		2.1510
onc201
TIC10 compound: a TRAIL-dependent antitumor agent; structure in first source		2.1710
ldc4297
LDC4297: a CDK7 inhibitor with antineoplastic activity; structure in first source. LDC4297 : A pyrazolotriazine that is pyrazolo[1,5-a][1,3,5]triazine substituted by a piperidin-3-yloxy group, [2-(1H-pyrazol-1-yl)benzyl]nitrilo group and an isopropyl group at positions 2, 4 and 8 respectively. It is a potent and selective CDK7 inhibitor and exhibits antiviral activity.		2.610aromatic ether;
piperidines;
pyrazoles;
pyrazolotriazine;
secondary amino compound		antineoplastic agent;
antiviral agent;
apoptosis inducer;
EC 2.7.11.22 (cyclin-dependent kinase) inhibitor
enasidenib
[no description available]		2.6101,3,5-triazines;
aminopyridine;
aromatic amine;
organofluorine compound;
secondary amino compound;
tertiary alcohol		antineoplastic agent;
EC 1.1.1.42 (isocitrate dehydrogenase) inhibitor
s 8932
[no description available]		2.610aromatic amine;
C-nucleoside;
carboxylic ester;
nitrile;
phosphoramidate ester;
pyrrolotriazine		anticoronaviral agent;
antiviral drug;
prodrug
cyclosporine
Cyclosporine: A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed).		2.1110
entecavir
entecavir (anhydrous) : Guanine substituted at the 9 position by a 4-hydroxy-3-(hydroxymethyl)-2-methylidenecyclopentyl group. A synthetic analogue of 2'-deoxyguanosine, it is a nucleoside reverse transcriptase inhibitor with selective antiviral activity against hepatitis B virus. Entecavir is phosphorylated intracellularly to the active triphosphate form, which competes with deoxyguanosine triphosphate, the natural substrate of hepatitis B virus reverse transcriptase, inhibiting every stage of the enzyme's activity, although it has no activity against HIV. It is used for the treatment of chronic hepatitis B.		2.6102-aminopurines;
oxopurine;
primary alcohol;
secondary alcohol		antiviral drug;
EC 2.7.7.49 (RNA-directed DNA polymerase) inhibitor
chir 258
[no description available]		2.0810
acyclovir
Acyclovir: A GUANOSINE analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes.. acyclovir : An oxopurine that is guanine substituted by a (2-hydroxyethoxy)methyl substituent at position 9. Used in the treatment of viral infections.		2.6102-aminopurines;
oxopurine		antimetabolite;
antiviral drug
osi 027
OSI 027: inhibits both mTORC1 and mTORC2; structure in first source		2.0810
nu 1025
NU 1064: structure in first source		2.610phenols;
quinazolines		EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor
rifampin
Rifampin: A semisynthetic antibiotic produced from Streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits DNA-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1160)		4.4811cyclic ketal;
hydrazone;
N-iminopiperazine;
N-methylpiperazine;
rifamycins;
semisynthetic derivative;
zwitterion		angiogenesis inhibitor;
antiamoebic agent;
antineoplastic agent;
antitubercular agent;
DNA synthesis inhibitor;
EC 2.7.7.6 (RNA polymerase) inhibitor;
Escherichia coli metabolite;
geroprotector;
leprostatic drug;
neuroprotective agent;
pregnane X receptor agonist;
protein synthesis inhibitor
didanosine
Didanosine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. Didanosine is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase; ddI is then metabolized to dideoxyadenosine triphosphate, its putative active metabolite.. didanosine : A purine 2',3'-dideoxyribonucleoside that is inosine in which the hydroxy groups at both the 2' and the 3' positions on the sugar moiety have been replaced by hydrogen. An antiviral drug, it is used as a medication to treat HIV/AIDS.		2.610purine 2',3'-dideoxyribonucleosideantimetabolite;
antiviral drug;
EC 2.4.2.1 (purine-nucleoside phosphorylase) inhibitor;
geroprotector;
HIV-1 reverse transcriptase inhibitor
ganciclovir
[no description available]		2.6102-aminopurines;
oxopurine		antiinfective agent;
antiviral drug
valacyclovir
Valacyclovir: A prodrug of acyclovir that is used in the treatment of HERPES ZOSTER and HERPES SIMPLEX VIRUS INFECTION of the skin and mucous membranes, including GENITAL HERPES.		2.610L-valyl esterantiviral drug
penciclovir
penciclovir : A member of the class of 2-aminopurines that is guanine in which the hydrogen at position 9 is substituted by a 4-hydroxy-3-(hydroxymethyl)but-1-yl group. An antiviral drug, it is administered topically for treatment of herpes labialis. A prodrug, famciclovir, is used for oral administration.		2.6102-aminopurines;
propane-1,3-diols		antiviral drug
hli 373
[no description available]		2.0810
4-hydroxyquinazoline
4-oxo-3,4-dihydroquinazoline: structure in first source		2.610quinazolines
tegaserod
tegaserod: a nonbenzamide 5-hydroxytryptamine(4) agonist; used in treatment of irritable bowel syndrome; marketing suspended 2007 in US due to higher incidence of MI, stroke, and unstable angina; structure given in first source		2.610carboxamidine;
guanidines;
hydrazines;
indoles		gastrointestinal drug;
serotonergic agonist
norclozapine
norclozapine: structure given in first source. N-desmethylclozapine : A dibenzodoazepine substituted with chloro and piperazino groups which is a major metabolite of clozapine; a potent and selective 5-HT2C serotonin receptor antagonist.		2.610dibenzodiazepine;
organochlorine compound;
piperazines		delta-opioid receptor agonist;
metabolite;
serotonergic antagonist
pemetrexed
pemetrexed disodium : An organic sodium salt that is the disodium salt of N-{4-[2-(2-amino-4-oxo-4,7-dihydro-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl}-L-glutamic acid. Inhibits thymidylate synthase (TS), 421 dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT).		2.5820N-acyl-L-glutamic acid;
pyrrolopyrimidine		antimetabolite;
antineoplastic agent;
EC 1.5.1.3 (dihydrofolate reductase) inhibitor;
EC 2.1.1.45 (thymidylate synthase) inhibitor;
EC 2.1.2.2 (phosphoribosylglycinamide formyltransferase) inhibitor
sildenafil citrate
Sildenafil Citrate: A PHOSPHODIESTERASE TYPE-5 INHIBITOR; VASODILATOR AGENT and UROLOGICAL AGENT that is used in the treatment of ERECTILE DYSFUNCTION and PRIMARY PULMONARY HYPERTENSION.. sildenafil citrate : The citrate salt of sildenafil.		2.0810citrate saltEC 3.1.4.35 (3',5'-cyclic-GMP phosphodiesterase) inhibitor;
vasodilator agent
aprepitant
Aprepitant: A morpholine neurokinin-1 (NK1) receptor antagonist that is used in the management of nausea and vomiting caused by DRUG THERAPY, and for the prevention of POSTOPERATIVE NAUSEA AND VOMITING.. aprepitant : A morpholine-based antiemetic, which is or the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy. Aprepitant is a selective high-affinity antagonist of human substance P/neurokinin 1 (NK1) receptors.		2.5820(trifluoromethyl)benzenes;
cyclic acetal;
morpholines;
triazoles		antidepressant;
antiemetic;
neurokinin-1 receptor antagonist;
peripheral nervous system drug;
substance P receptor antagonist
azilsartan
azilsartan: an angiotensin type 1 receptor blocker; receptor blocker. azilsartan : A benzimidazolecarboxylic acid that is benzimidazole-7-carboxylic acid substituted at position 2 by a methoxy group and at position 1 by a 2'-[(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl group. Used (as the prodrug, azilsartan medoxomil) for treatment of hypertension.		2.6101,2,4-oxadiazole;
aromatic ether;
benzimidazolecarboxylic acid		angiotensin receptor antagonist;
antihypertensive agent
xav939
XAV939: selectively inhibits beta-catenin-mediated transcription; structure in first source. XAV939 : A thiopyranopyrimidine in which a 7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine skeleton is substituted at C-4 by a hydroxy group and at C-2 by a para-(trifluoromethyl)phenyl group.		2.0810(trifluoromethyl)benzenes;
thiopyranopyrimidine		tankyrase inhibitor
2-carboxyarabinitol 1-phosphate
[no description available]		2.0810
hesperadin
[no description available]		2.610
nintedanib
nintedanib : A member of the class of oxindoles that is a kinase inhibitor used (in the form of its ethylsulfonate salt) for the treatment of idiopathic pulmonary fibrosis and cancer.		2.0810
6-bromoindirubin-3'-acetoxime
6-bromoindirubin-3'-acetoxime: a synthetic derivative of a compound from the Mediterranean mollusk Hexaplex trunculus, protects cells from varicella infection		2.610
n'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazide
[no description available]		2.610catechols;
hydrazide;
hydrazone;
naphthols		EC 3.6.5.5 (dynamin GTPase) inhibitor
ver 52296
luminespib : A monocarboxylic acid amide obtained by formal condensation of the carboxy group of 5-(2,4-dihydroxy-5-isopropylphenyl)-4-[4-(morpholin-4-ylmethyl)phenyl]-1,2-oxazole-3-carboxylic acid with the amino group of ethylamine.		2.0810aromatic amide;
isoxazoles;
monocarboxylic acid amide;
morpholines;
resorcinols		angiogenesis inhibitor;
antineoplastic agent;
Hsp90 inhibitor
sb-590885
N-{5-[2-{4-[2-(dimethylamino)ethoxy]phenyl}-4-(pyridin-4-yl)-1H-imidazol-5-yl]-2,3-dihydro-1H-inden-1-ylidene}hydroxylamine : A ketoxime that is the oxime of indan-1-one in which the hydrogen at position 5 has been replaced by an imidazol-5-yl group which has itself been substituted at positions 2 and 4 by p-[2-(dimethylamino)ethoxy]phenyl and pyridin-4-yl groups, respectively.		2.0810aromatic ether;
imidazoles;
ketoxime;
pyridines;
tertiary amino compound
XL413
XL413 : A benzofuropyrimidine that is 3,4-dihydro[1]benzofuro[3,2-d]pyrimidine substituted by (2S)-pyrrolidin-2-yl, oxo and chloro groups at positions 2, 4, and 8, respectively. It is a potent ATP competitive inhibitor of Cdc7 kinase (IC50 = 3.4 nM) and exhibits anticancer properties.		2.610benzofuropyrimidine;
organochlorine compound;
pyrrolidines		antineoplastic agent;
EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor
pf-477736
PF 00477736: a Chk1 inhibitor; structure in first source. PF-00477736 : A diazepinoindole that is 8-amino-4,5-dihydro-6H-[1,2]diazepino[4,5,6-cd]indol-6-one which is substituted at position 2 by a 1-methylpyrazol-4-yl group and in which the amino group at position 8 has undergone condensation with the carboxy group of (2R)-2-cyclohexylglycine to give the corresponding carboxamide. It is an inhibitor of checkpoint kinase 1 (Chk 1).		2.0810
me0328
ME0328: inhibits ARTD3; structure in first source		2.610
fenobam
fenobam: in USAN fenobam refers to monohydrate		2.0810ureas
nvp-tnks656
[no description available]		2.610
phenanthrenes
Phenanthrenes: POLYCYCLIC AROMATIC HYDROCARBONS composed of three fused BENZENE rings.. phenanthrenes : Any benzenoid aromatic compound that consists of a phenanthrene skeleton and its substituted derivatives thereof.		2.3110
ConditionIndicatedRelationship StrengthStudiesTrials
Genetic Diseases
[description not available]		02.1510
Genetic Diseases, Inborn
Diseases that are caused by genetic mutations present during embryo or fetal development, although they may be observed later in life. The mutations may be inherited from a parent's genome or they may be acquired in utero.		02.1510
Kahler Disease
[description not available]		020.9820588
Experimental Neoplasms
[description not available]		02.1710
Multiple Myeloma
A malignancy of mature PLASMA CELLS engaging in monoclonal immunoglobulin production. It is characterized by hyperglobulinemia, excess Bence-Jones proteins (free monoclonal IMMUNOGLOBULIN LIGHT CHAINS) in the urine, skeletal destruction, bone pain, and fractures. Other features include ANEMIA; HYPERCALCEMIA; and RENAL INSUFFICIENCY.		122.9820588
Hematologic Malignancies
[description not available]		011.0151
Autoimmune Disease
[description not available]		03.1210
Autoimmune Diseases
Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.		03.1210
Hematologic Neoplasms
Neoplasms located in the blood and blood-forming tissue (the bone marrow and lymphatic tissue). The commonest forms are the various types of LEUKEMIA, of LYMPHOMA, and of the progressive, life-threatening forms of the MYELODYSPLASTIC SYNDROMES.		18.0151
Infections, Staphylococcal Skin
[description not available]		02.2510
Staphylococcal Skin Infections
Infections to the skin caused by bacteria of the genus STAPHYLOCOCCUS.		02.2510
Congenital Zika Syndrome
[description not available]		02.2510
Disease Models, Animal
Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.		03.2550
Zika Virus Infection
A viral disease transmitted by the bite of AEDES mosquitoes infected with ZIKA VIRUS. Its mild DENGUE-like symptoms include fever, rash, headaches and ARTHRALGIA. The viral infection during pregnancy, in rare cases, is associated with congenital brain and ocular abnormalities, called Congenital Zika Syndrome, including MICROCEPHALY and may also lead to GUILLAIN-BARRE SYNDROME.		02.2510
Breast Cancer
[description not available]		07.9830
Breast Neoplasms
Tumors or cancer of the human BREAST.		02.9830
Atypical Lipomatous Tumor
[description not available]		02.3110
Liposarcoma
A malignant tumor derived from primitive or embryonal lipoblastic cells. It may be composed of well-differentiated fat cells or may be dedifferentiated: myxoid (LIPOSARCOMA, MYXOID), round-celled, or pleomorphic, usually in association with a rich network of capillaries. Recurrences are common and dedifferentiated liposarcomas metastasize to the lungs or serosal surfaces. (From Dorland, 27th ed; Stedman, 25th ed)		02.3110
Hepatocellular Carcinoma
[description not available]		07.1710
Cancer of Liver
[description not available]		02.1710
Carcinoma, Hepatocellular
A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested.		02.1710
Liver Neoplasms
Tumors or cancer of the LIVER.		02.1710
Carcinoma, Epidermoid
[description not available]		02.6620
Cancer of Lung
[description not available]		02.8730
Carcinoma, Squamous Cell
A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed)		02.6620
Lung Neoplasms
Tumors or cancer of the LUNG.		02.8730
Granulocytic Leukemia, Chronic
[description not available]		02.6120
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Clonal hematopoetic disorder caused by an acquired genetic defect in PLURIPOTENT STEM CELLS. It starts in MYELOID CELLS of the bone marrow, invades the blood and then other organs. The condition progresses from a stable, more indolent, chronic phase (LEUKEMIA, MYELOID, CHRONIC PHASE) lasting up to 7 years, to an advanced phase composed of an accelerated phase (LEUKEMIA, MYELOID, ACCELERATED PHASE) and BLAST CRISIS.		02.6120
Diffuse Large B-Cell Lymphoma
[description not available]		02.1510
Lymphoma, Large B-Cell, Diffuse
Malignant lymphoma composed of large B lymphoid cells whose nuclear size can exceed normal macrophage nuclei, or more than twice the size of a normal lymphocyte. The pattern is predominantly diffuse. Most of these lymphomas represent the malignant counterpart of B-lymphocytes at midstage in the process of differentiation.		02.1510
Osteogenic Sarcoma
[description not available]		02.5720
Osteosarcoma
A sarcoma originating in bone-forming cells, affecting the ends of long bones. It is the most common and most malignant of sarcomas of the bones, and occurs chiefly among 10- to 25-year-old youths. (From Stedman, 25th ed)		02.5720
Benign Neoplasms
[description not available]		011.14168
Neoplasms
New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.		115.73216
Local Neoplasm Recurrence
[description not available]		014.624726
Anemia
A reduction in the number of circulating ERYTHROCYTES or in the quantity of HEMOGLOBIN.		0421
Neutropenia
A decrease in the number of NEUTROPHILS found in the blood.		05.7832
Graft-Versus-Host Disease
[description not available]		08.0284
Graft vs Host Disease
The clinical entity characterized by anorexia, diarrhea, loss of hair, leukopenia, thrombocytopenia, growth retardation, and eventual death brought about by the GRAFT VS HOST REACTION.		08.0284
Leukocytopenia
[description not available]		04.0221
Thrombopenia
[description not available]		011.761513
Diarrhea
An increased liquidity or decreased consistency of FECES, such as running stool. Fecal consistency is related to the ratio of water-holding capacity of insoluble solids to total water, rather than the amount of water present. Diarrhea is not hyperdefecation or increased fecal weight.		011.9753
Leukopenia
A decrease in the number of LEUKOCYTES in a blood sample below the normal range (LEUKOCYTE COUNT less than 4000).		04.0221
Thrombocytopenia
A subnormal level of BLOOD PLATELETS.		011.761513
Cancer of Esophagus
[description not available]		02.4110
Esophageal Neoplasms
Tumors or cancer of the ESOPHAGUS.		02.4110
Leukemia, Lymphoblastic, Acute, T Cell
[description not available]		02.3110
Leukemia, Pre-B-Cell
[description not available]		02.3110
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
A leukemia/lymphoma found predominately in children and adolescents and characterized by a high number of lymphoblasts and solid tumor lesions. Frequent sites involve LYMPH NODES, skin, and bones. It most commonly presents as leukemia.		02.3110
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
A leukemia/lymphoma found predominately in children and young adults and characterized LYMPHADENOPATHY and THYMUS GLAND involvement. It most frequently presents as a lymphoma, but a leukemic progression in the bone marrow is common.		02.3110
Cholera Infantum
[description not available]		0420
Infection
[description not available]		03.2310
Infections
Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.		03.2310
Acute Lymphoid Leukemia
[description not available]		03.0730
Precursor Cell Lymphoblastic Leukemia-Lymphoma
A neoplasm characterized by abnormalities of the lymphoid cell precursors leading to excessive lymphoblasts in the marrow and other organs. It is the most common cancer in children and accounts for the vast majority of all childhood leukemias.		15.6360
Exanthem
[description not available]		010.221210
Exanthema
Diseases in which skin eruptions or rashes are a prominent manifestation. Classically, six such diseases were described with similar rashes; they were numbered in the order in which they were reported. Only the fourth (Duke's disease), fifth (ERYTHEMA INFECTIOSUM), and sixth (EXANTHEMA SUBITUM) numeric designations survive as occasional synonyms in current terminology.		010.221210
Crow-Fukase Syndrome
[description not available]		02.8220
POEMS Syndrome
A multisystemic disorder characterized by a sensorimotor polyneuropathy (POLYNEUROPATHIES), organomegaly, endocrinopathy, monoclonal gammopathy, and pigmentary skin changes. Other clinical features which may be present include EDEMA; CACHEXIA; microangiopathic glomerulopathy; pulmonary hypertension (HYPERTENSION, PULMONARY); cutaneous necrosis; THROMBOCYTOSIS; and POLYCYTHEMIA. This disorder is frequently associated with osteosclerotic myeloma. (From Adams et al., Principles of Neurology, 6th ed, p1335; Rev Med Interne 1997;18(7):553-62)		07.8220
Amyloidosis
A group of sporadic, familial and/or inherited, degenerative, and infectious disease processes, linked by the common theme of abnormal protein folding and deposition of AMYLOID. As the amyloid deposits enlarge they displace normal tissue structures, causing disruption of function. Various signs and symptoms depend on the location and size of the deposits.		08.5466
Asymptomatic Multiple Myeloma
[description not available]		02.8220
Smoldering Multiple Myeloma
An asymptomatic and slow-growing PLASMA CELL dyscrasia characterized by presence of MYELOMA PROTEINS and clonal bone marrow plasma cells without end-organ damage (e.g., renal impairment). It is distinguished from MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE by a much higher risk of progression to symptomatic MULTIPLE MYELOMA.		02.8220
AL Amyloidosis
[description not available]		07.3573
Immunoglobulin Light-chain Amyloidosis
A nonproliferative disorder of the PLASMA CELL characterized by excessive production and misfolding of IMMUNOGLOBULIN LIGHT CHAINS that form insoluble amyloid fibrils (see AMYLOID DEPOSITS) in various tissues. Clinical features include LIVER FAILURE; MULTIPLE MYELOMA; NEPHROTIC SYNDROME; RESTRICTIVE CARDIOMYOPATHY, and neuropathies.		07.3573
Abnormalities, Autosome
[description not available]		09.886
Cardiac Toxicity
[description not available]		04.140
Cardiotoxicity
Damage to the HEART or its function secondary to exposure to toxic substances such as drugs used in CHEMOTHERAPY; IMMUNOTHERAPY; or RADIATION.		09.140
Diseases of Endocrine System
[description not available]		02.4110
Benign Monoclonal Gammopathies
[description not available]		02.4110
Endocrine System Diseases
Pathological processes of the ENDOCRINE GLANDS, and diseases resulting from abnormal level of available HORMONES.		02.4110
Minimal Disease, Residual
[description not available]		09.5175
Diffuse Lymphocytic Lymphoma, Poorly-Differentiated
[description not available]		04.9421
Lymphoma, Mantle-Cell
A form of non-Hodgkin lymphoma having a usually diffuse pattern with both small and medium lymphocytes and small cleaved cells. It accounts for about 5% of adult non-Hodgkin lymphomas in the United States and Europe. The majority of mantle-cell lymphomas are associated with a t(11;14) translocation resulting in overexpression of the CYCLIN D1 gene (GENES, BCL-1).		16.9421
Peripheral Nerve Diseases
[description not available]		06.3243
Peripheral Nervous System Diseases
Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.		06.3243
Lymphoma of Mucosa-Associated Lymphoid Tissue
[description not available]		06.8990
2019 Novel Coronavirus Disease
[description not available]		06.8990
Brill-Symmers Disease
[description not available]		08.29101
Lymphoma, Follicular
Malignant lymphoma in which the lymphomatous cells are clustered into identifiable nodules within the LYMPH NODES. The nodules resemble to some extent the GERMINAL CENTER of lymph node follicles and most likely represent neoplastic proliferation of lymph node-derived follicular center B-LYMPHOCYTES.		110.29101
Lymphoma, B-Cell, Marginal Zone
Extranodal lymphoma of lymphoid tissue associated with mucosa that is in contact with exogenous antigens. Many of the sites of these lymphomas, such as the stomach, salivary gland, and thyroid, are normally devoid of lymphoid tissue. They acquire mucosa-associated lymphoid tissue (MALT) type as a result of an immunologically mediated disorder.		06.8990
Benign Meningeal Neoplasms
[description not available]		02.610
Angioblastic Meningioma
[description not available]		02.610
Neurilemoma
[description not available]		02.610
Acoustic Neurinoma, Bilateral
[description not available]		02.610
Meningeal Neoplasms
Benign and malignant neoplastic processes that arise from or secondarily involve the meningeal coverings of the brain and spinal cord.		02.610
Meningioma
A relatively common neoplasm of the CENTRAL NERVOUS SYSTEM that arises from arachnoidal cells. The majority are well differentiated vascular tumors which grow slowly and have a low potential to be invasive, although malignant subtypes occur. Meningiomas have a predilection to arise from the parasagittal region, cerebral convexity, sphenoidal ridge, olfactory groove, and SPINAL CANAL. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2056-7)		02.610
Neurilemmoma
A neoplasm that arises from SCHWANN CELLS of the cranial, peripheral, and autonomic nerves. Clinically, these tumors may present as a cranial neuropathy, abdominal or soft tissue mass, intracranial lesion, or with spinal cord compression. Histologically, these tumors are encapsulated, highly vascular, and composed of a homogenous pattern of biphasic fusiform-shaped cells that may have a palisaded appearance. (From DeVita Jr et al., Cancer: Principles and Practice of Oncology, 5th ed, pp964-5)		02.610
Neurofibromatosis 2
An autosomal dominant disorder characterized by a high incidence of bilateral acoustic neuromas as well as schwannomas (NEURILEMMOMA) of other cranial and peripheral nerves, and other benign intracranial tumors including meningiomas, ependymomas, spinal neurofibromas, and gliomas. The disease has been linked to mutations of the NF2 gene (GENES, NEUROFIBROMATOSIS 2) on chromosome 22 (22q12) and usually presents clinically in the first or second decade of life.		02.610
Auricular Fibrillation
[description not available]		02.610
Cardiac Failure
[description not available]		03.8230
Atrial Fibrillation
Abnormal cardiac rhythm that is characterized by rapid, uncoordinated firing of electrical impulses in the upper chambers of the heart (HEART ATRIA). In such case, blood cannot be effectively pumped into the lower chambers of the heart (HEART VENTRICLES). It is caused by abnormal impulse generation.		02.610
Heart Failure
A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.		03.8230
Bone Loss, Osteoclastic
[description not available]		03.9821
Debility
[description not available]		03.9911
Recrudescence
[description not available]		011.27166
Familial Waldenstrom's Macroglobulinaemia
[description not available]		06.941
Waldenstrom Macroglobulinemia
A lymphoproliferative disorder characterized by pleomorphic B-LYMPHOCYTES including PLASMA CELLS, with increased levels of monoclonal serum IMMUNOGLOBULIN M. There is lymphoplasmacytic cells infiltration into bone marrow and often other tissues, also known as lymphoplasmacytic lymphoma. Clinical features include ANEMIA; HEMORRHAGES; and hyperviscosity.		18.941
Granuloma, Hodgkin
[description not available]		02.5820
T-Cell Lymphoma
[description not available]		07.8430
Hodgkin Disease
A malignant disease characterized by progressive enlargement of the lymph nodes, spleen, and general lymphoid tissue. In the classical variant, giant usually multinucleate Hodgkin's and REED-STERNBERG CELLS are present; in the nodular lymphocyte predominant variant, lymphocytic and histiocytic cells are seen.		02.5820
Lymphoma, T-Cell
A group of heterogeneous lymphoid tumors representing malignant transformations of T-lymphocytes.		02.8430
Acute Febrile Neutrophilic Dermatosis
[description not available]		02.9430
Cell Transformation, Neoplastic
Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.		02.2110
Malignant Melanoma
[description not available]		02.5720
Melanoma
A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445)		07.5720
Gastrointestinal Stromal Neoplasm
[description not available]		02.2510
Gastrointestinal Stromal Tumors
All tumors in the GASTROINTESTINAL TRACT arising from mesenchymal cells (MESODERM) except those of smooth muscle cells (LEIOMYOMA) or Schwann cells (SCHWANNOMA).		02.2510
Heart Disease, Ischemic
[description not available]		02.5820
Myocardial Ischemia
A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (CORONARY ARTERY DISEASE), to obstruction by a thrombus (CORONARY THROMBOSIS), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (MYOCARDIAL INFARCTION).		07.5820
Chronic Illness
[description not available]		05.5222
Chronic Disease
Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care (Dictionary of Health Services Management, 2d ed). For epidemiological studies chronic disease often includes HEART DISEASES; STROKE; CANCER; and diabetes (DIABETES MELLITUS, TYPE 2).		05.5222
Symptom Cluster
[description not available]		02.2510
Syndrome
A characteristic symptom complex.		07.2510
Chicken Pox
[description not available]		02.2510
Shingles
[description not available]		02.2510
Chickenpox
A highly contagious infectious disease caused by the varicella-zoster virus (HERPESVIRUS 3, HUMAN). It usually affects children, is spread by direct contact or respiratory route via droplet nuclei, and is characterized by the appearance on the skin and mucous membranes of successive crops of typical pruritic vesicular lesions that are easily broken and become scabbed. Chickenpox is relatively benign in children, but may be complicated by pneumonia and encephalitis in adults. (From Dorland, 27th ed)		02.2510
Herpes Zoster
An acute infectious, usually self-limited, disease believed to represent activation of latent varicella-zoster virus (HERPESVIRUS 3, HUMAN) in those who have been rendered partially immune after a previous attack of CHICKENPOX. It involves the SENSORY GANGLIA and their areas of innervation and is characterized by severe neuralgic pain along the distribution of the affected nerve and crops of clustered vesicles over the area. (From Dorland, 27th ed)		02.2510
Blood Pressure, High
[description not available]		03.3310
Hypertension
Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.		03.3310
Tumour Lysis Syndrome
[description not available]		02.2510
Tumor Lysis Syndrome
A syndrome resulting from cytotoxic therapy, occurring generally in aggressive, rapidly proliferating lymphoproliferative disorders. It is characterized by combinations of hyperuricemia, lactic acidosis, hyperkalemia, hyperphosphatemia and hypocalcemia.		07.2510
Becker Muscular Dystrophy
[description not available]		02.3110
Muscular Dystrophy, Duchenne
An X-linked recessive muscle disease caused by an inability to synthesize DYSTROPHIN, which is involved with maintaining the integrity of the sarcolemma. Muscle fibers undergo a process that features degeneration and regeneration. Clinical manifestations include proximal weakness in the first few years of life, pseudohypertrophy, cardiomyopathy (see MYOCARDIAL DISEASES), and an increased incidence of impaired mentation. Becker muscular dystrophy is a closely related condition featuring a later onset of disease (usually adolescence) and a slowly progressive course. (Adams et al., Principles of Neurology, 6th ed, p1415)		02.3110
Chalazia
[description not available]		07.3110
Blepharitis
Inflammation of the eyelids.		07.3110
Chalazion
A non-neoplastic cyst of the MEIBOMIAN GLANDS of the eyelid.		02.3110
Acute Myelogenous Leukemia
[description not available]		04.4941
Leukemia, Myeloid, Acute
Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.		16.4941
Pyoderma Gangrenosum
An idiopathic, rapidly evolving, and severely debilitating disease occurring most commonly in association with chronic ulcerative colitis. It is characterized by the presence of boggy, purplish ulcers with undermined borders, appearing mostly on the legs. The majority of cases are in people between 40 and 60 years old. Its etiology is unknown.		07.4110
Adenocarcinoma, Basal Cell
[description not available]		02.1510
Cancer of Colon
[description not available]		02.5320
Adenocarcinoma
A malignant epithelial tumor with a glandular organization.		02.1510
Colonic Neoplasms
Tumors or cancer of the COLON.		02.5320
Bladder Cancer
[description not available]		07.1510
Urinary Bladder Neoplasms
Tumors or cancer of the URINARY BLADDER.		02.1510
Dermatitis Medicamentosa
[description not available]		03.5311
Blood Diseases
[description not available]		04.8721
Emesis
[description not available]		06.0533
Hematologic Diseases
Disorders of the blood and blood forming tissues.		04.8721
Nausea
An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses.		012.7155
Vomiting
The forcible expulsion of the contents of the STOMACH through the MOUTH.		011.0533
Lassitude
[description not available]		06.8233
Germinoblastoma
[description not available]		06.3542
Fatigue
The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.		06.8233
Lymphoma
A general term for various neoplastic diseases of the lymphoid tissue.		18.3542
Cutaneous T-Cell Lymphoma
[description not available]		03.5311
Lymphoma, T Cell, Peripheral
[description not available]		05.3922
Lymphoma, T-Cell, Cutaneous
A group of lymphomas exhibiting clonal expansion of malignant T-lymphocytes arrested at varying stages of differentiation as well as malignant infiltration of the skin. MYCOSIS FUNGOIDES; SEZARY SYNDROME; LYMPHOMATOID PAPULOSIS; and PRIMARY CUTANEOUS ANAPLASTIC LARGE CELL LYMPHOMA are the best characterized of these disorders.		03.5311
Lymphoma, T-Cell, Peripheral
A group of malignant lymphomas thought to derive from peripheral T-lymphocytes in lymph nodes and other nonlymphoid sites. They include a broad spectrum of lymphocyte morphology, but in all instances express T-cell markers admixed with epithelioid histiocytes, plasma cells, and eosinophils. Although markedly similar to large-cell immunoblastic lymphoma (LYMPHOMA, LARGE-CELL, IMMUNOBLASTIC), this group's unique features warrant separate treatment.		05.3922
Angiitis
[description not available]		02.6120
Vasculitis
Inflammation of any one of the blood vessels, including the ARTERIES; VEINS; and rest of the vasculature system in the body.		07.6120
Disease Exacerbation
[description not available]		08.877
Bone Cancer
[description not available]		02.1710
Canine Diseases
[description not available]		02.1710
Bone Neoplasms
Tumors or cancer located in bone tissue or specific BONES.		02.1710
Curling Ulcer
Acute stress DUODENAL ULCER, usually observed in patients with extensive third-degree burns.		02.2510
Jejunal Diseases
Pathological development in the JEJUNUM region of the SMALL INTESTINE.		02.2510
Cryoglobulinemia
A condition characterized by the presence of abnormal quantities of CRYOGLOBULINS in the blood. Upon cold exposure, these abnormal proteins precipitate into the microvasculature leading to restricted blood flow in the exposed areas.		02.2510
Duodenal Ulcer
A PEPTIC ULCER located in the DUODENUM.		02.2510
Ulcer
A lesion on the surface of the skin or a mucous surface, produced by the sloughing of inflammatory necrotic tissue.		02.2510
Colorectal Cancer
[description not available]		07.5920
Colorectal Neoplasms
Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI.		02.5920
ER-Negative PR-Negative HER2-Negative Breast Cancer
[description not available]		04.4811
Metastase
[description not available]		04.4811
Neoplasm Metastasis
The transfer of a neoplasm from one organ or part of the body to another remote from the primary site.		04.4811
Triple Negative Breast Neoplasms
Breast neoplasms that do not express ESTROGEN RECEPTORS; PROGESTERONE RECEPTORS; and do not overexpress the NEU RECEPTOR/HER-2 PROTO-ONCOGENE PROTEIN.		16.4811
EBV Infections
[description not available]		02.2110
B-Cell Lymphoma
[description not available]		02.5220
Lymphoma, B-Cell
A group of heterogeneous lymphoid tumors generally expressing one or more B-cell antigens or representing malignant transformations of B-lymphocytes.		02.5220
Epstein-Barr Virus Infections
Infection with human herpesvirus 4 (HERPESVIRUS 4, HUMAN); which may facilitate the development of various lymphoproliferative disorders. These include BURKITT LYMPHOMA (African type), INFECTIOUS MONONUCLEOSIS, and oral hairy leukoplakia (LEUKOPLAKIA, HAIRY).		02.2110
Colonic Inertia
Symptom characterized by the passage of stool once a week or less.		03.5911
Constipation
Infrequent or difficult evacuation of FECES. These symptoms are associated with a variety of causes, including low DIETARY FIBER intake, emotional or nervous disturbances, systemic and structural disorders, drug-induced aggravation, and infections.		08.5911
Adenocarcinoma Of Kidney
[description not available]		02.2110
Cancer of Kidney
[description not available]		02.2110
Carcinoma, Renal Cell
A heterogeneous group of sporadic or hereditary carcinoma derived from cells of the KIDNEYS. There are several subtypes including the clear cells, the papillary, the chromophobe, the collecting duct, the spindle cells (sarcomatoid), or mixed cell-type carcinoma.		14.2110
Kidney Neoplasms
Tumors or cancers of the KIDNEY.		02.2110
Duncan Disease
[description not available]		03.1210
Lymphoproliferative Disorders
Disorders characterized by proliferation of lymphoid tissue, general or unspecified.		08.1210
B-Cell Chronic Lymphocytic Leukemia
[description not available]		02.110
Leukemia, Lymphocytic, Chronic, B-Cell
A chronic leukemia characterized by abnormal B-lymphocytes and often generalized lymphadenopathy. In patients presenting predominately with blood and bone marrow involvement it is called chronic lymphocytic leukemia (CLL); in those predominately with enlarged lymph nodes it is called small lymphocytic lymphoma. These terms represent spectrums of the same disease.		02.110
Androgen-Independent Prostatic Cancer
[description not available]		02.110
Prostatic Neoplasms, Castration-Resistant
Tumors or cancer of the PROSTATE which can grow in the presence of low or residual amount of androgen hormones such as TESTOSTERONE.		02.110
Acute Disease
Disease having a short and relatively severe course.		02.1110
Glomerulonephritis, Lupus
[description not available]		03.0310
Lupus Nephritis
Glomerulonephritis associated with autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Lupus nephritis is histologically classified into 6 classes: class I - normal glomeruli, class II - pure mesangial alterations, class III - focal segmental glomerulonephritis, class IV - diffuse glomerulonephritis, class V - diffuse membranous glomerulonephritis, and class VI - advanced sclerosing glomerulonephritis (The World Health Organization classification 1982).		15.0310
Carcinoma, Non-Small Cell Lung
[description not available]		02.1110
Carcinoma, Non-Small-Cell Lung
A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.		02.1110
Liver Dysfunction
[description not available]		03.5111
Liver Diseases
Pathological processes of the LIVER.		03.5111
Kidney Failure
A severe irreversible decline in the ability of kidneys to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism.		03.5111
Chronic Kidney Failure
[description not available]		03.5111
Kidney Failure, Chronic
The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION.		03.5111
Renal Insufficiency
Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE.		03.5111
Cancer of Skin
[description not available]		02.1310
Skin Neoplasms
Tumors or cancer of the SKIN.		02.1310
Thrombotic Microangiopathies
Diseases that result in THROMBOSIS in MICROVASCULATURE. The two most prominent diseases are PURPURA, THROMBOTIC THROMBOCYTOPENIC; and HEMOLYTIC-UREMIC SYNDROME. Multiple etiological factors include VASCULAR ENDOTHELIAL CELL damage due to SHIGA TOXIN; FACTOR H deficiency; and aberrant VON WILLEBRAND FACTOR formation.		02.1510
Osteolysis
Dissolution of bone that particularly involves the removal or loss of calcium.		02.0610
Neoplasms, Plasma Cell
Neoplasms associated with a proliferation of a single clone of PLASMA CELLS and characterized by the secretion of PARAPROTEINS.		02.0610