Compounds > sar405838
Page last updated: 2024-11-13

sar405838

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Description

SAR405838: an inhibitor of the interaction of MDM2 and p53; has antineoplastic activity; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID53476877
CHEMBL ID2381408
CHEMBL ID3961782
SCHEMBL ID3704267
SCHEMBL ID5585402
SCHEMBL ID10188383
SCHEMBL ID12230015
MeSH IDM000600711

Synonyms (52)

Synonym
(2's,3'r,4's,5'r)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro [indole-3,3'-pyrrolidine]-5'-carboxylic acid (trans-4-hydroxy-cyclohexyl)-amide
IDKAKZRYYDCJDU-HBMMIIHUSA-N
(2's,3'r,4's,5'r)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid (trans-4-hydroxy-cyclohexyl)-amide
chembl2381408 ,
bdbm50433561
S7649
sar-405838
sar 405838
sar405838
mi-77301
SCHEMBL3704267
SCHEMBL5585402
CS-5003
bdbm119726
us8680132, mi- 77301 (free amine)
us8680132, mi- 77301 (tfa salt)
bdbm119727
SCHEMBL10188383
SCHEMBL12230015
(2's,3r,4's,5'r)-6-chloro-4'-(3-chloro-2-fluorophenyl)-2'-(2,2-dimethylpropyl)-n-(trans-4-hydroxycyclohexyl)-2-oxo-1,2-dihydrospiro(indole-3,3'-pyrrolidine)-5'-carboxamide
sar 405838 [who-dd]
8570LZ3RCA ,
1303607-60-4
(2's,3'r,4's,5'r)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro (indole-3,3'-pyrrolidine)-5'-carboxylic acid (trans-4-hydroxy-cyclohexyl)-amide
spiro(3h-indole-3,3'-pyrrolidine)-5'-carboxamide, 6-chloro-4'-(3-chloro-2-fluorophenyl)-2'-(2,2-dimethylpropyl)-1,2-dihydro-n-(trans-4-hydroxycyclohexyl)-2-oxo-, (2's,3r,4's,5'r)-
unii-8570lz3rca
mi-773 (sar405838)
AC-32665
HY-18986
J-690122
5-[(1-ethyl-2,2,6,6-tetramethyl-4-piperidinyl)oxy]-n-[4-({[5-(2-methyl-2-propanyl)-1,2-oxazol-3-yl]carbamoyl}amino)phenyl]-2-pyridin ecarboxamide
sar405838 (mi-77301)
EX-A659
AKOS030526391
mi773
mi 773
(2's,3r,4's,5'r)-6-chloro-4'-(3-chloro-2-fluorophenyl)-2'-(2,2-dimethylpropyl)-n-(trans-4-hydroxycyclohexyl)-2-oxo-1,2-dihydrospiro[indole-3,3'-pyrrolidine]-5'-carboxamide
7hc ,
(2's,3r,4's,5'r)-6-chloro-4'-(3-chloro-2-fluorophenyl)-n-((1r,4r)-4-hydroxycyclohexyl)-2'-neopentyl-2-oxospiro[indoline-3,3'-pyrrolidine]-5'-carboxamide
mfcd28976052
DB12541
CHEMBL3961782
IDKAKZRYYDCJDU-AEPXTFJPSA-N ,
AMY19461
sar405838 (mi-773)
(2'r,3r,3's,5's)-6-chloro-3'-(3-chloro-2-fluorophenyl)-5'-(2,2-dimethylpropyl)-n-(4-hydroxycyclohexyl)-2-oxospiro[1h-indole-3,4'-pyrrolidine]-2'-carboxamide
(2's,3r,4's,5'r)-6-chloro-4'-(3-chloro-2-fluorophenyl)-2'-(2,2-dimethylpropyl)-1,2-dihydro-n-(trans-4-hydroxycyclohexyl)-2-oxospiro[3h-indole-3,3'-pyrrolidine]-5'-carboxamide
CCG-264716
Q27269599
MS-30203
(2's,3r,4's,5'r)-6-chloro-4'-(3-chloro-2-fluorophenyl)-2'-(2,2-dimethylpropyl)-1,2-dihydro-n-(trans-4-hydroxycyclohexyl)-2-oxo-spiro[3h-indole-3,3'-pyrrolidine]-5'-carboxamide;sar405838
A888769

Research Excerpts

Overview

SAR405838 is a potent and specific MDM2 inhibitor currently being evaluated in Phase I clinical trials for the treatment of human cancer.

ExcerptReferenceRelevance
"SAR405838 is a potent and specific MDM2 inhibitor currently being evaluated in Phase I clinical trials for the treatment of human cancer. "( Significant Differences in the Development of Acquired Resistance to the MDM2 Inhibitor SAR405838 between In Vitro and In Vivo Drug Treatment.
Debussche, L; Hoffman-Luca, CG; Lu, J; McEachern, D; Wang, S; Yang, CY; Ziazadeh, D, 2015)		2.08

Treatment

ExcerptReferenceRelevance
"Treatment with SAR405838 was associated with increased plasma MIC-1, reflecting p53 pathway activation."( A phase I study of SAR405838, a novel human double minute 2 (HDM2) antagonist, in patients with solid tumours.
de Jonge, M; de Weger, VA; Dickson, MA; Hsu, K; Langenberg, M; Le Cesne, A; Macé, S; Schellens, JH; Thomas, K; Tuffal, G; Wagner, AJ; Zheng, W, 2017)		1.12

Compound-Compound Interactions

ExcerptReferenceRelevance
" No significant drug-drug interactions were observed."( A phase I study of the HDM2 antagonist SAR405838 combined with the MEK inhibitor pimasertib in patients with advanced solid tumours.
de Jonge, M; de Weger, VA; Demers, B; Deutsch, E; Goodstal, S; Hsu, K; Langenberg, MHG; Lolkema, M; Macé, S; Schellens, JHM; Thomas, K; Tuffal, G; Varga, A, 2019)		0.78
[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)
E3 ubiquitin-protein ligase Mdm2Homo sapiens (human)IC50 (µMol)0.10000.00060.358210.0000AID1692744
E3 ubiquitin-protein ligase Mdm2Homo sapiens (human)Ki0.00200.00090.19811.2400AID1195730; AID1420859; AID1422083; AID1434519; AID1555897; AID1692743; AID1807822; AID746381
[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)
E3 ubiquitin-protein ligase Mdm2Homo sapiens (human)Kd0.00270.00000.25851.0000AID1075196
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (64)

Processvia Protein(s)Taxonomy
regulation of cell cycleE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
ubiquitin-dependent protein catabolic processE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
negative regulation of transcription by RNA polymerase IIE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
protein polyubiquitinationE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
blood vessel developmentE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
blood vessel remodelingE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
regulation of heart rateE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
atrioventricular valve morphogenesisE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
endocardial cushion morphogenesisE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
ventricular septum developmentE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
atrial septum developmentE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
ubiquitin-dependent protein catabolic processE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
apoptotic processE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrestE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
traversing start control point of mitotic cell cycleE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
positive regulation of cell population proliferationE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
response to xenobiotic stimulusE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
response to toxic substanceE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
response to iron ionE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
positive regulation of gene expressionE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
negative regulation of protein processingE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
negative regulation of neuron projection developmentE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
protein ubiquitinationE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
protein sumoylationE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
protein destabilizationE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
response to magnesium ionE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
positive regulation of proteasomal ubiquitin-dependent protein catabolic processE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
protein localization to nucleusE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
regulation of protein catabolic processE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
response to cocaineE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
proteasome-mediated ubiquitin-dependent protein catabolic processE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
negative regulation of DNA damage response, signal transduction by p53 class mediatorE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
establishment of protein localizationE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
response to etherE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
negative regulation of DNA-templated transcriptionE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
positive regulation of mitotic cell cycleE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
response to antibioticE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
positive regulation of protein export from nucleusE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
response to steroid hormoneE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
positive regulation of muscle cell differentiationE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
proteolysis involved in protein catabolic processE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
protein autoubiquitinationE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
cardiac septum morphogenesisE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
protein-containing complex assemblyE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
cellular response to hydrogen peroxideE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
cellular response to vitamin B1E3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
cellular response to alkaloidE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
cellular response to growth factor stimulusE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
cellular response to peptide hormone stimulusE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
cellular response to estrogen stimulusE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
cellular response to hypoxiaE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
cellular response to gamma radiationE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
cellular response to UV-CE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
fibroblast activationE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
cellular response to actinomycin DE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
negative regulation of signal transduction by p53 class mediatorE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
negative regulation of intrinsic apoptotic signaling pathway by p53 class mediatorE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
response to formaldehydeE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
positive regulation of vascular associated smooth muscle cell proliferationE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
positive regulation of vascular associated smooth muscle cell migrationE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
amyloid fibril formationE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
response to water-immersion restraint stressE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
negative regulation of apoptotic processE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
cell cycleE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
regulation of gene expressionE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (18)

Processvia Protein(s)Taxonomy
p53 bindingE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
ubiquitin-protein transferase activityE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
protein bindingE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
5S rRNA bindingE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
zinc ion bindingE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
ligase activityE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
SUMO transferase activityE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
enzyme bindingE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
protein domain specific bindingE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
ubiquitin protein ligase bindingE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
receptor serine/threonine kinase bindingE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
identical protein bindingE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
peroxisome proliferator activated receptor bindingE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
ribonucleoprotein complex bindingE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
ubiquitin bindingE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
ubiquitin protein ligase activityE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
NEDD8 ligase activityE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
disordered domain specific bindingE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (10)

Processvia Protein(s)Taxonomy
nuclear bodyE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
nucleusE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
nucleoplasmE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
nucleolusE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
cytoplasmE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
cytosolE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
plasma membraneE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
transcription repressor complexE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
endocytic vesicle membraneE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
protein-containing complexE3 ubiquitin-protein ligase Mdm2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (40)

Assay IDTitleYearJournalArticle
AID1443819Chemical stability of compound in 1:1 MeOH to H2O solution assessed as isomerization by measuring compound purity retainment after 7 days by UPLC analysis2017Journal of medicinal chemistry, 04-13, Volume: 60, Issue:7
Discovery of 4-((3'R,4'S,5'R)-6″-Chloro-4'-(3-chloro-2-fluorophenyl)-1'-ethyl-2″-oxodispiro[cyclohexane-1,2'-pyrrolidine-3',3″-indoline]-5'-carboxamido)bicyclo[2.2.2]octane-1-carboxylic Acid (AA-115/APG-115): A Potent and Orally Active Murine Double Minut
AID1420859Inhibition of FAM-tagged p53-based fluorescent probe binding to human His-tagged MDM2 (1 to 118 residues) after 15 mins by fluorescence polarization assay2018European journal of medicinal chemistry, Oct-05, Volume: 158Role of p53 circuitry in tumorigenesis: A brief review.
AID1443823Clearance in rat at 5 mg/kg, iv2017Journal of medicinal chemistry, 04-13, Volume: 60, Issue:7
Discovery of 4-((3'R,4'S,5'R)-6″-Chloro-4'-(3-chloro-2-fluorophenyl)-1'-ethyl-2″-oxodispiro[cyclohexane-1,2'-pyrrolidine-3',3″-indoline]-5'-carboxamido)bicyclo[2.2.2]octane-1-carboxylic Acid (AA-115/APG-115): A Potent and Orally Active Murine Double Minut
AID1195731Cytotoxicity against human SJSA1 cells2015Journal of medicinal chemistry, Feb-12, Volume: 58, Issue:3
Small-molecule inhibitors of the MDM2-p53 protein-protein interaction (MDM2 Inhibitors) in clinical trials for cancer treatment.
AID1195735Cytotoxicity against human RS4:11 cells2015Journal of medicinal chemistry, Feb-12, Volume: 58, Issue:3
Small-molecule inhibitors of the MDM2-p53 protein-protein interaction (MDM2 Inhibitors) in clinical trials for cancer treatment.
AID1392507Induction of apoptosis in human HCT116 p53+ cells at 5 uM by Annexin V-FITC staining-based flow cytometric analysis relative to Nutlin-3a2018Bioorganic & medicinal chemistry, 05-15, Volume: 26, Issue:9
Design, in silico prioritization and biological profiling of apoptosis-inducing lactams amenable by the Castagnoli-Cushman reaction.
AID1392511Antiproliferative activity against human HCT116 p53+/+ cells assessed as growth inhibition after 24 hrs by EdU/Hoechst 33342 staining-based fluorescence analysis2018Bioorganic & medicinal chemistry, 05-15, Volume: 26, Issue:9
Design, in silico prioritization and biological profiling of apoptosis-inducing lactams amenable by the Castagnoli-Cushman reaction.
AID1392509Activation of p53 in human U2OS cells harboring p53-dependent EGFP reporter gene assessed as increase in p53 transcriptional activity at 5 uM after 48 hrs by propidium iodide satining-based automated fluorescent imaging analysis relative to Nutlin-3a2018Bioorganic & medicinal chemistry, 05-15, Volume: 26, Issue:9
Design, in silico prioritization and biological profiling of apoptosis-inducing lactams amenable by the Castagnoli-Cushman reaction.
AID1555897Binding affinity to MDM2 (unknown origin)2019European journal of medicinal chemistry, Aug-15, Volume: 176Development of selective small molecule MDM2 degraders based on nutlin.
AID1129365Cytotoxicity against human SJSA1 cells assessed as growth inhibition after 16 hrs by EdU incorporation assay in presence of 10% human serum2014Journal of medicinal chemistry, Apr-10, Volume: 57, Issue:7
Novel inhibitors of the MDM2-p53 interaction featuring hydrogen bond acceptors as carboxylic acid isosteres.
AID1443822AUC in rat at 5 mg/kg, iv2017Journal of medicinal chemistry, 04-13, Volume: 60, Issue:7
Discovery of 4-((3'R,4'S,5'R)-6″-Chloro-4'-(3-chloro-2-fluorophenyl)-1'-ethyl-2″-oxodispiro[cyclohexane-1,2'-pyrrolidine-3',3″-indoline]-5'-carboxamido)bicyclo[2.2.2]octane-1-carboxylic Acid (AA-115/APG-115): A Potent and Orally Active Murine Double Minut
AID1443790Cmax in rat at 25 mg/kg, po2017Journal of medicinal chemistry, 04-13, Volume: 60, Issue:7
Discovery of 4-((3'R,4'S,5'R)-6″-Chloro-4'-(3-chloro-2-fluorophenyl)-1'-ethyl-2″-oxodispiro[cyclohexane-1,2'-pyrrolidine-3',3″-indoline]-5'-carboxamido)bicyclo[2.2.2]octane-1-carboxylic Acid (AA-115/APG-115): A Potent and Orally Active Murine Double Minut
AID746381Binding affinity to human MDM22013Bioorganic & medicinal chemistry letters, May-01, Volume: 23, Issue:9
Inhibitors of the p53/hdm2 protein-protein interaction-path to the clinic.
AID1443821In vivo induction of MDM2 upregulation in human SJSA1 cell tumor xenografted in SCID mouse at 100 mg/kg administered as single dose through oral gavage measured at 6 and 24 hrs post last dose by Western blot analysis2017Journal of medicinal chemistry, 04-13, Volume: 60, Issue:7
Discovery of 4-((3'R,4'S,5'R)-6″-Chloro-4'-(3-chloro-2-fluorophenyl)-1'-ethyl-2″-oxodispiro[cyclohexane-1,2'-pyrrolidine-3',3″-indoline]-5'-carboxamido)bicyclo[2.2.2]octane-1-carboxylic Acid (AA-115/APG-115): A Potent and Orally Active Murine Double Minut
AID1392512Antiproliferative activity against human HCT116 p53-/- cells assessed as growth inhibition after 24 hrs by EdU/Hoechst 33342 staining-based fluorescence analysis2018Bioorganic & medicinal chemistry, 05-15, Volume: 26, Issue:9
Design, in silico prioritization and biological profiling of apoptosis-inducing lactams amenable by the Castagnoli-Cushman reaction.
AID1195736Cytotoxicity against human LNCAP cells2015Journal of medicinal chemistry, Feb-12, Volume: 58, Issue:3
Small-molecule inhibitors of the MDM2-p53 protein-protein interaction (MDM2 Inhibitors) in clinical trials for cancer treatment.
AID1443796Oral bioavailability in rat at 25 mg/kg2017Journal of medicinal chemistry, 04-13, Volume: 60, Issue:7
Discovery of 4-((3'R,4'S,5'R)-6″-Chloro-4'-(3-chloro-2-fluorophenyl)-1'-ethyl-2″-oxodispiro[cyclohexane-1,2'-pyrrolidine-3',3″-indoline]-5'-carboxamido)bicyclo[2.2.2]octane-1-carboxylic Acid (AA-115/APG-115): A Potent and Orally Active Murine Double Minut
AID1443825In vivo induction of ubiquitinated-MDM2 upregulation in human SJSA1 cell tumor xenografted in SCID mouse at 100 mg/kg administered as single dose through oral gavage measured at 6 and 24 hrs post last dose by Western blot analysis2017Journal of medicinal chemistry, 04-13, Volume: 60, Issue:7
Discovery of 4-((3'R,4'S,5'R)-6″-Chloro-4'-(3-chloro-2-fluorophenyl)-1'-ethyl-2″-oxodispiro[cyclohexane-1,2'-pyrrolidine-3',3″-indoline]-5'-carboxamido)bicyclo[2.2.2]octane-1-carboxylic Acid (AA-115/APG-115): A Potent and Orally Active Murine Double Minut
AID1443820Chemical stability of compound in cell culture media assessed as isomerization by measuring compound purity retainment after 7 days by UPLC analysis2017Journal of medicinal chemistry, 04-13, Volume: 60, Issue:7
Discovery of 4-((3'R,4'S,5'R)-6″-Chloro-4'-(3-chloro-2-fluorophenyl)-1'-ethyl-2″-oxodispiro[cyclohexane-1,2'-pyrrolidine-3',3″-indoline]-5'-carboxamido)bicyclo[2.2.2]octane-1-carboxylic Acid (AA-115/APG-115): A Potent and Orally Active Murine Double Minut
AID1443785Antitumor activity against human SJSA1 cells xenografted in SCID mouse assessed as tumor growth inhibition at 50 mg/kg dosed via oral gavage administered qd for 14 days2017Journal of medicinal chemistry, 04-13, Volume: 60, Issue:7
Discovery of 4-((3'R,4'S,5'R)-6″-Chloro-4'-(3-chloro-2-fluorophenyl)-1'-ethyl-2″-oxodispiro[cyclohexane-1,2'-pyrrolidine-3',3″-indoline]-5'-carboxamido)bicyclo[2.2.2]octane-1-carboxylic Acid (AA-115/APG-115): A Potent and Orally Active Murine Double Minut
AID1443786Antitumor activity against human SJSA1 cells xenografted in SCID mouse assessed as tumor regression at 100 mg/kg dosed via oral gavage administered qd for 14 days2017Journal of medicinal chemistry, 04-13, Volume: 60, Issue:7
Discovery of 4-((3'R,4'S,5'R)-6″-Chloro-4'-(3-chloro-2-fluorophenyl)-1'-ethyl-2″-oxodispiro[cyclohexane-1,2'-pyrrolidine-3',3″-indoline]-5'-carboxamido)bicyclo[2.2.2]octane-1-carboxylic Acid (AA-115/APG-115): A Potent and Orally Active Murine Double Minut
AID1434519Inhibition of PMDM6-F binding to recombinant human His-tagged MDM2 (1 to 118 residues) after 15 mins by fluorescence polarization assay2017European journal of medicinal chemistry, Jan-27, Volume: 126Discovery of novel polycyclic spiro-fused carbocyclicoxindole-based anticancer agents.
AID1692743Inhibition of FAM tagged p53-based peptide binding to recombinant human His-tagged MDM2 protein (residues 1 to 118 residues) incubated for 15 mins by fluorescence-polarization-based binding assay2020Journal of medicinal chemistry, 11-25, Volume: 63, Issue:22
Opportunities for Tapping into Three-Dimensional Chemical Space through a Quaternary Carbon.
AID1443826In vivo induction of p21 upregulation in human SJSA1 cell tumor xenografted in SCID mouse at 100 mg/kg administered as single dose through oral gavage measured at 6 and 24 hrs post last dose by Western blot analysis2017Journal of medicinal chemistry, 04-13, Volume: 60, Issue:7
Discovery of 4-((3'R,4'S,5'R)-6″-Chloro-4'-(3-chloro-2-fluorophenyl)-1'-ethyl-2″-oxodispiro[cyclohexane-1,2'-pyrrolidine-3',3″-indoline]-5'-carboxamido)bicyclo[2.2.2]octane-1-carboxylic Acid (AA-115/APG-115): A Potent and Orally Active Murine Double Minut
AID1443792Half life in rat at 25 mg/kg, po2017Journal of medicinal chemistry, 04-13, Volume: 60, Issue:7
Discovery of 4-((3'R,4'S,5'R)-6″-Chloro-4'-(3-chloro-2-fluorophenyl)-1'-ethyl-2″-oxodispiro[cyclohexane-1,2'-pyrrolidine-3',3″-indoline]-5'-carboxamido)bicyclo[2.2.2]octane-1-carboxylic Acid (AA-115/APG-115): A Potent and Orally Active Murine Double Minut
AID1195730Binding affinity to MDM2 (unknown origin)2015Journal of medicinal chemistry, Feb-12, Volume: 58, Issue:3
Small-molecule inhibitors of the MDM2-p53 protein-protein interaction (MDM2 Inhibitors) in clinical trials for cancer treatment.
AID1443798In vivo induction of cleaved PARP upregulation in human SJSA1 cell tumor xenografted in SCID mouse at 100 mg/kg administered as single dose through oral gavage measured at 6 and 24 hrs post last dose by Western blot analysis2017Journal of medicinal chemistry, 04-13, Volume: 60, Issue:7
Discovery of 4-((3'R,4'S,5'R)-6″-Chloro-4'-(3-chloro-2-fluorophenyl)-1'-ethyl-2″-oxodispiro[cyclohexane-1,2'-pyrrolidine-3',3″-indoline]-5'-carboxamido)bicyclo[2.2.2]octane-1-carboxylic Acid (AA-115/APG-115): A Potent and Orally Active Murine Double Minut
AID1443799In vivo induction of cleaved caspase-3 upregulation in human SJSA1 cell tumor xenografted in SCID mouse at 100 mg/kg administered as single dose through oral gavage measured at 6 and 24 hrs post last dose by Western blot analysis2017Journal of medicinal chemistry, 04-13, Volume: 60, Issue:7
Discovery of 4-((3'R,4'S,5'R)-6″-Chloro-4'-(3-chloro-2-fluorophenyl)-1'-ethyl-2″-oxodispiro[cyclohexane-1,2'-pyrrolidine-3',3″-indoline]-5'-carboxamido)bicyclo[2.2.2]octane-1-carboxylic Acid (AA-115/APG-115): A Potent and Orally Active Murine Double Minut
AID1195738Antitumor activity against human SJSA1 cells xenografted in mouse assessed as tumor regression at 200 mg/kg, po2015Journal of medicinal chemistry, Feb-12, Volume: 58, Issue:3
Small-molecule inhibitors of the MDM2-p53 protein-protein interaction (MDM2 Inhibitors) in clinical trials for cancer treatment.
AID1692744Inhibition of MDM2 (unknown origin) by cell-based assay2020Journal of medicinal chemistry, 11-25, Volume: 63, Issue:22
Opportunities for Tapping into Three-Dimensional Chemical Space through a Quaternary Carbon.
AID1443791AUC in rat at 25 mg/kg, po2017Journal of medicinal chemistry, 04-13, Volume: 60, Issue:7
Discovery of 4-((3'R,4'S,5'R)-6″-Chloro-4'-(3-chloro-2-fluorophenyl)-1'-ethyl-2″-oxodispiro[cyclohexane-1,2'-pyrrolidine-3',3″-indoline]-5'-carboxamido)bicyclo[2.2.2]octane-1-carboxylic Acid (AA-115/APG-115): A Potent and Orally Active Murine Double Minut
AID1422083Inhibition of MDM2 (unknown origin)2018European journal of medicinal chemistry, Nov-05, Volume: 159The development of piperidinones as potent MDM2-P53 protein-protein interaction inhibitors for cancer therapy.
AID1195732Cytotoxicity against human HCT116 cells2015Journal of medicinal chemistry, Feb-12, Volume: 58, Issue:3
Small-molecule inhibitors of the MDM2-p53 protein-protein interaction (MDM2 Inhibitors) in clinical trials for cancer treatment.
AID1807822Binding affinity to recombinant human His6-tagged HDM2 (1 to 118 residues) assessed as reduction in PMDM6-F binding incubated for 15 to 30 mins by fluorescence polarization assay2021Journal of medicinal chemistry, 11-11, Volume: 64, Issue:21
Discovery of
AID1195737Antitumor activity against human LNCAP cells xenografted in mouse assessed as tumor regression at 100 mg/kg, po2015Journal of medicinal chemistry, Feb-12, Volume: 58, Issue:3
Small-molecule inhibitors of the MDM2-p53 protein-protein interaction (MDM2 Inhibitors) in clinical trials for cancer treatment.
AID1443797In vivo induction of p53 activation in human SJSA1 cell tumor xenografted in SCID mouse at 100 mg/kg administered as single dose through oral gavage measured at 6 and 24 hrs post last dose by Western blot analysis2017Journal of medicinal chemistry, 04-13, Volume: 60, Issue:7
Discovery of 4-((3'R,4'S,5'R)-6″-Chloro-4'-(3-chloro-2-fluorophenyl)-1'-ethyl-2″-oxodispiro[cyclohexane-1,2'-pyrrolidine-3',3″-indoline]-5'-carboxamido)bicyclo[2.2.2]octane-1-carboxylic Acid (AA-115/APG-115): A Potent and Orally Active Murine Double Minut
AID1443818Chemical stability of compound in 1:1 CH3CN to H2O solution assessed as isomerization by measuring compound purity retainment after 7 days by UPLC analysis2017Journal of medicinal chemistry, 04-13, Volume: 60, Issue:7
Discovery of 4-((3'R,4'S,5'R)-6″-Chloro-4'-(3-chloro-2-fluorophenyl)-1'-ethyl-2″-oxodispiro[cyclohexane-1,2'-pyrrolidine-3',3″-indoline]-5'-carboxamido)bicyclo[2.2.2]octane-1-carboxylic Acid (AA-115/APG-115): A Potent and Orally Active Murine Double Minut
AID1075195Antiproliferative activity against human SJSA1 cells assessed as inhibition of EdU incorporation after 1 hr by Click-iT EdU HCS assay in presence of 10% human serum2014Journal of medicinal chemistry, Feb-27, Volume: 57, Issue:4
Discovery of AMG 232, a potent, selective, and orally bioavailable MDM2-p53 inhibitor in clinical development.
AID1075196Binding affinity to human MDM2 by by Surface Plasmon Resonace (SPR) spectroscopy binding assay2014Journal of medicinal chemistry, Feb-27, Volume: 57, Issue:4
Discovery of AMG 232, a potent, selective, and orally bioavailable MDM2-p53 inhibitor in clinical development.
AID1443824Volume of distribution in steady state in rat at 5 mg/kg, iv2017Journal of medicinal chemistry, 04-13, Volume: 60, Issue:7
Discovery of 4-((3'R,4'S,5'R)-6″-Chloro-4'-(3-chloro-2-fluorophenyl)-1'-ethyl-2″-oxodispiro[cyclohexane-1,2'-pyrrolidine-3',3″-indoline]-5'-carboxamido)bicyclo[2.2.2]octane-1-carboxylic Acid (AA-115/APG-115): A Potent and Orally Active Murine Double Minut
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (30)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's0 (0.00)29.6817
2010's27 (90.00)24.3611
2020's3 (10.00)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 22.65

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 Index22.65 (24.57)
Research Supply Index3.53 (2.92)
Research Growth Index4.53 (4.65)
Search Engine Demand Index23.28 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (22.65)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials3 (10.00%)5.53%
Reviews7 (23.33%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other20 (66.67%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]
SubstanceRelationship StrengthStudiesTrialsClassesRoles
niacinamide
nicotinamide : A pyridinecarboxamide that is pyridine in which the hydrogen at position 3 is replaced by a carboxamide group.		4.8821pyridine alkaloid;
pyridinecarboxamide;
vitamin B3		anti-inflammatory agent;
antioxidant;
cofactor;
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor;
EC 3.5.1.98 (histone deacetylase) inhibitor;
Escherichia coli metabolite;
geroprotector;
human urinary metabolite;
metabolite;
mouse metabolite;
neuroprotective agent;
Saccharomyces cerevisiae metabolite;
Sir2 inhibitor
1,3-dipropyl-8-cyclopentylxanthine
DPCPX : An oxopurine that is 7H-xanthine substituted at positions 1 and 3 by propyl groups and at position 8 by a cyclohexyl group.		3.3510oxopurineadenosine A1 receptor antagonist;
EC 3.1.4.* (phosphoric diester hydrolase) inhibitor
4-aminobenzoic acid
para-Aminobenzoates: Benzoic acids, salts, or esters that contain an amino group attached to carbon number 4 of the benzene ring structure.. 4-aminobenzoate : An aromatic amino-acid anion that is the conjugate base of 4-aminobenzoic acid.		3.2510aminobenzoate;
aromatic amino-acid anion		Escherichia coli metabolite;
plant metabolite;
Saccharomyces cerevisiae metabolite
cytarabine
[no description available]		3.2710beta-D-arabinoside;
monosaccharide derivative;
pyrimidine nucleoside		antimetabolite;
antineoplastic agent;
antiviral agent;
immunosuppressive agent
indazoles
Indazoles: A group of heterocyclic aromatic organic compounds consisting of the fusion of BENZENE and PYRAZOLES.		3.2310indazole
2-piperidone
2-piperidone: structure given in first source. piperidin-2-one : A delta-lactam that is piperidine which is substituted by an oxo group at position 2.		2.1710delta-lactam;
piperidones		EC 1.2.1.88 (L-glutamate gamma-semialdehyde dehydrogenase) inhibitor
phenyl acetate
phenyl acetate: The ester formed between phenol and acetic acid. Don't confuse with phenylacetic acid derivatives listed under PHENYLACETATES.. phenyl acetate : An acetate ester obtained by the formal condensation of phenol with acetic acid.		2.1710benzenes;
phenyl acetates
cp 424391
CP 424391: a growth hormone secretagogue; structure in first source		3.3510
nutlin 2
[no description available]		3.2110
nutlin 1
nutlin 1: an MDM2 antagonist; structure in first source		3.6220
abt-737
[no description available]		2.1110aromatic amine;
aryl sulfide;
biphenyls;
C-nitro compound;
monochlorobenzenes;
N-arylpiperazine;
N-sulfonylcarboxamide;
secondary amino compound;
tertiary amino compound		anti-allergic agent;
anti-inflammatory agent;
antineoplastic agent;
apoptosis inducer;
B-cell lymphoma 2 inhibitor
nutlin-3a
nutlin 3: an MDM2 antagonist; structure in first source		4.9960stilbenoid
pb 12
[no description available]		3.2110
rg7388
RG7388: structure in first source		4.3550
rg7112
[no description available]		4.8550
amg 232
[no description available]		4.3450
nitrophenols
Nitrophenols: PHENOLS carrying nitro group substituents.		2.1110
mi-219
MI-219: an MDM2 inhibitor; structure in first source		2.5320
ConditionIndicatedRelationship StrengthStudiesTrials
Bone Cancer
[description not available]		02.5220
Osteogenic Sarcoma
[description not available]		02.8130
Bone Neoplasms
Tumors or cancer located in bone tissue or specific BONES.		02.5220
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)		02.8130
Benign Neoplasms
[description not available]		08.4462
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.		08.4462
Leucocythaemia
[description not available]		02.5320
Leukemia
A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006)		02.5320
Carcinogenesis
The origin, production or development of cancer through genotypic and phenotypic changes which upset the normal balance between cell proliferation and cell death. Carcinogenesis generally requires a constellation of steps, which may occur quickly or over a period of many years.		03.0910
Benign Neoplasms, Brain
[description not available]		02.5920
Brain Neoplasms
Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain.		02.5920
Carcinoma, Non-Small Cell Lung
[description not available]		04.8621
Lassitude
[description not available]		04.4511
Cancer of Gastrointestinal Tract
[description not available]		04.4511
Atypical Lipomatous Tumor
[description not available]		05.6932
Cancer of Lung
[description not available]		04.8621
Malignant Melanoma
[description not available]		04.4511
Cancer of Skin
[description not available]		04.4511
Thrombopenia
[description not available]		06.1832
Emesis
[description not available]		04.4511
Anorexia
The lack or loss of APPETITE accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder ANOREXIA NERVOSA.		04.4511
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.		04.8621
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.		04.4511
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)		05.6932
Lung Neoplasms
Tumors or cancer of the LUNG.		04.8621
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)		04.4511
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.		04.4511
Skin Neoplasms
Tumors or cancer of the SKIN.		04.4511
Thrombocytopenia
A subnormal level of BLOOD PLATELETS.		06.1832
Vomiting
The forcible expulsion of the contents of the STOMACH through the MOUTH.		04.4511
Carcinoma, Papillary
A malignant neoplasm characterized by the formation of numerous, irregular, finger-like projections of fibrous stroma that is covered with a surface layer of neoplastic epithelial cells. (Stedman, 25th ed)		02.1510
Disease Models, Animal
Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.		02.5420
Cancer of the Thyroid
[description not available]		02.1510
Thyroid Neoplasms
Tumors or cancer of the THYROID GLAND.		02.1510
Hematologic Malignancies
[description not available]		03.0610
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.		03.0610
Colorectal Cancer
[description not available]		02.1510
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.		02.1510
Astrocytoma, Grade IV
[description not available]		02.1710
Glioblastoma
A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures.		07.1710
Local Neoplasm Recurrence
[description not available]		02.1310
Response Evaluation Criteria in Solid Tumors
An internationally recognized set of published rules used for evaluation of cancer treatment that define when tumors found in cancer patients improve, worsen, or remain stable during treatment. These criteria are based specifically on the response of the tumor(s) to treatment, and not on the overall health status of the patient resulting from treatment.		03.5111
Neuroblastoma
A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51)		07.1310
Breast Cancer
[description not available]		02.1310
Breast Neoplasms
Tumors or cancer of the human BREAST.		02.1310