Page last updated: 2024-11-13

kpt-185

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

KPT-185: binds CRM1 to inhibit nuclear export; has antineoplastic activity [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID53495165
CHEMBL ID3898452
SCHEMBL ID1335182
MeSH IDM0579400

Synonyms (24)

Synonym
SCHEMBL1335182
S7125
(z)-isopropyl 3-(3-(3-methoxy-5-(trifluoromethyl)phenyl)-1h-1,2,4-triazol-1-yl)acrylate
1333151-73-7
kpt-185
kpt185
AC-32679
n-[3-({2-[(4-{[1-(2-fluoroethyl)-3-azetidinyl]amino}-2-methoxyphenyl)amino]-5-(trifluoromethyl)-4-pyrimidinyl}amino)phenyl]acrylamid e
J-690131
EX-A318
AKOS030526414
kpt 185
NCGC00386294-01
CHEMBL3898452
SW219337-1
isopropyl (z)-3-(3-(3-methoxy-5-(trifluoromethyl)phenyl)-1h-1,2,4-triazol-1-yl)acrylate
CCG-268093
propan-2-yl (z)-3-[3-[3-methoxy-5-(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]prop-2-enoate
nsc-757568
nsc757568
nsc772595
nsc-772595
nlngwflrrrynil-plngdyqasa-n
HY-15611

Research Excerpts

Bioavailability

ExcerptReferenceRelevance
" Orally bioavailable selective inhibitors of nuclear export (SINE) that irreversibly bind to CRM1 and block the function of this protein have been recently developed."( Preclinical activity of a novel CRM1 inhibitor in acute myeloid leukemia.
Blum, W; Caligiuri, M; Croce, CM; Garzon, R; Kauffman, M; Klisovic, R; Marcucci, G; Na, C; Ranganathan, P; Santhanam, R; Shacham, S; Walker, A; Yu, X, 2012
)
0.38
" The orally bioavailable SINE (KPT-251) showed potent anti-tumor activity in a Colo-357 PDAC xenografts model; residual tumor analysis showed activation of Fbw7 concomitant with attenuation of Notch1 and its downstream genes."( Nuclear retention of Fbw7 by specific inhibitors of nuclear export leads to Notch1 degradation in pancreatic cancer.
Abou-Samra, AB; Aboukameel, A; Azmi, AS; Gao, J; Kauffman, M; Mohammad, RM; Shacham, S, 2014
)
0.4
" Inhibition of the exportin-1 (XPO1) mediated nuclear transport by clinical stage orally bioavailable small molecule inhibitors (SINE) prevented the nuclear export of the late intron-containing HIV RNA species and consequently potently suppressed viral replication."( Human Exportin-1 is a Target for Combined Therapy of HIV and AIDS Related Lymphoma.
Andrei, G; Boons, E; Daelemans, D; Jacquemyn, M; Landesman, Y; Neggers, JE; Nogueira, TC; Pannecouque, C; Shacham, S; Snoeck, R; Tamir, S; van den Oord, J; Vanstreels, E; Vercruysse, T, 2015
)
0.42
"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

ExcerptRelevanceReference
" Binding to XPO1 was quantitated from SINE compound treated adherent and suspension cells in vitro, dosed ex vivo human peripheral blood mononuclear cells (PBMCs), and PBMCs from mice dosed orally with drug in vivo."( A method for quantification of exportin-1 (XPO1) occupancy by Selective Inhibitor of Nuclear Export (SINE) compounds.
Baloglu, E; Crochiere, ML; Del Alamo, D; Donovan, S; Kauffman, M; Klebanov, B; Landesman, Y; Lee, M; Shacham, S, 2016
)
0.43
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (1)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Exportin-1Homo sapiens (human)IC50 (µMol)1.00000.00100.58401.6000AID1339772
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (11)

Processvia Protein(s)Taxonomy
protein export from nucleusExportin-1Homo sapiens (human)
ribosomal subunit export from nucleusExportin-1Homo sapiens (human)
ribosomal large subunit export from nucleusExportin-1Homo sapiens (human)
ribosomal small subunit export from nucleusExportin-1Homo sapiens (human)
mRNA export from nucleusExportin-1Homo sapiens (human)
protein export from nucleusExportin-1Homo sapiens (human)
nucleocytoplasmic transportExportin-1Homo sapiens (human)
regulation of centrosome duplicationExportin-1Homo sapiens (human)
regulation of proteasomal ubiquitin-dependent protein catabolic processExportin-1Homo sapiens (human)
protein localization to nucleusExportin-1Homo sapiens (human)
ribosome biogenesisExportin-1Homo sapiens (human)
regulation of protein export from nucleusExportin-1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (4)

Processvia Protein(s)Taxonomy
RNA bindingExportin-1Homo sapiens (human)
nuclear export signal receptor activityExportin-1Homo sapiens (human)
protein bindingExportin-1Homo sapiens (human)
small GTPase bindingExportin-1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (14)

Processvia Protein(s)Taxonomy
kinetochoreExportin-1Homo sapiens (human)
nuclear envelopeExportin-1Homo sapiens (human)
annulate lamellaeExportin-1Homo sapiens (human)
nucleoplasmExportin-1Homo sapiens (human)
nucleolusExportin-1Homo sapiens (human)
cytoplasmExportin-1Homo sapiens (human)
cytosolExportin-1Homo sapiens (human)
Cajal bodyExportin-1Homo sapiens (human)
membraneExportin-1Homo sapiens (human)
nuclear membraneExportin-1Homo sapiens (human)
intracellular membrane-bounded organelleExportin-1Homo sapiens (human)
protein-containing complexExportin-1Homo sapiens (human)
ribonucleoprotein complexExportin-1Homo sapiens (human)
nucleusExportin-1Homo sapiens (human)
cytoplasmExportin-1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (5)

Assay IDTitleYearJournalArticle
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.
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.
AID1347160Primary screen NINDS Rhodamine 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.
AID1347159Primary screen GU Rhodamine qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay2020Proceedings 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.
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.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (24)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's0 (0.00)29.6817
2010's21 (87.50)24.3611
2020's3 (12.50)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 18.90

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 moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index18.90 (24.57)
Research Supply Index3.26 (2.92)
Research Growth Index4.52 (4.65)
Search Engine Demand Index15.26 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (18.90)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials1 (4.17%)5.53%
Reviews0 (0.00%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other23 (95.83%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]