Details of the Drug

General Information of Drug (ID: DM65PTO)

Drug Name

AMG 232

Synonyms

KRT-232

Indication

Disease Entry	ICD 11	Status	REF
Merkel cell carcinoma	2C34	Phase 2	[1]
Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[2]
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Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 2

Molecular Weight (mw)

568.6

Logarithm of the Partition Coefficient (xlogp)

5.8

Rotatable Bond Count (rotbonds)

9

Hydrogen Bond Donor Count (hbonddonor)

1

Hydrogen Bond Acceptor Count (hbondacc)

5

Chemical Identifiers

Formula: C28H35Cl2NO5S
IUPAC Name: 2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-1-[(2S)-3-methyl-1-propan-2-ylsulfonylbutan-2-yl]-2-oxopiperidin-3-yl]acetic acid
Canonical SMILES: CC(C)[C@@H](CS(=O)(=O)C(C)C)N1[C@@H]([C@H](C[C@](C1=O)(C)CC(=O)O)C2=CC(=CC=C2)Cl)C3=CC=C(C=C3)Cl
InChI: InChI=1S/C28H35Cl2NO5S/c1-17(2)24(16-37(35,36)18(3)4)31-26(19-9-11-21(29)12-10-19)23(20-7-6-8-22(30)13-20)14-28(5,27(31)34)15-25(32)33/h6-13,17-18,23-24,26H,14-16H2,1-5H3,(H,32,33)/t23-,24-,26-,28-/m1/s1
InChIKey: DRLCSJFKKILATL-YWCVFVGNSA-N

Cross-matching ID

Repurposed Drugs (RPD)

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Ubiquitin-protein ligase E3 Mdm2 (MDM2)	TT08GJW	MDM2_HUMAN	Modulator	[3]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Drug Response	[4]
Nestin (NES)	OTZ9PZ14	NEST_HUMAN	Gene/Protein Processing	[4]
Zinc finger E-box-binding homeobox 1	OTEDXTGD	ZEB1_HUMAN	Gene/Protein Processing	[4]

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Molecular Interaction Atlas (MIA)

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Merkel cell carcinoma

ICD Disease Classification

2C34

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Ubiquitin-protein ligase E3 Mdm2 (MDM2)	DTT	MDM2	1.19E-04	0.05	0.16

Molecular Expression Atlas (MEA)

Jump to Detail Molecular Expression Atlas of This Drug

References

1	ClinicalTrials.gov (NCT03787602) This Study Evaluates KRT-232, a Novel Oral Small Molecule Inhibitor of MDM2, for the Treatment of Patients With (p53WT) Merkel Cell Carcinoma Who Have Failed Anti-PD-1/ PD-L1 Immunotherapy. U.S. National Institutes of Health.
2	ClinicalTrials.gov (NCT02110355) A Phase 1b/2a Study Evaluating AMG 232 in Metastatic Melanoma. U.S. National Institutes of Health.
3	Discovery of a small molecule MDM2 inhibitor (AMG 232) for treating cancer. J Med Chem. 2014 Aug 14;57(15):6332-41.
4	Potent effect of the MDM2 inhibitor AMG232 on suppression of glioblastoma stem cells. Cell Death Dis. 2018 Jul 18;9(8):792. doi: 10.1038/s41419-018-0825-1.