Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM65PTO)

• Drug Name: AMG 232 Drug Info
• 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]

• Cross-matching ID:
  PubChem CID: 58573469
  ChEBI ID: CHEMBL3125702
  CAS Number: CAS 1352066-68-2
  TTD Drug ID: DM65PTO

Molecule-Related Drug Atlas

Drug(s) Targeting Ubiquitin-protein ligase E3 Mdm2 (MDM2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
RG7388	DMF5GZI	Acute myeloid leukaemia	2A60	Phase 3	[5]
APG-115	DMIFA0L	Prolymphocytic leukaemia	2A82.1	Phase 2	[6]
ALRN-6924	DMLBWT1	Haematological malignancy	2B33.Y	Phase 2	[6]
ASTX295	DM9EM5G	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[7]
HDM201	DMVRTCW	Haematological malignancy	2B33.Y	Phase 1	[6]
DS-3032	DMA2B5Y	Haematological malignancy	2B33.Y	Phase 1	[8]
RG7775	DMXBS6U	Acute myeloid leukaemia	2A60	Phase 1	[9]
JNJ-26854165	DMNSJ3C	Non-small-cell lung cancer	2C25.Y	Phase 1	[10]
BI 907828	DM2Z4YQ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[11]
MI-219	DM196LK	Triple negative breast cancer	2C60-2C65	Investigative	[12]

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]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Zinc finger E-box-binding homeobox 1	OTEDXTGD	ZEB1_HUMAN	Gene/Protein Processing	[4]

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.
• [5] Pre-clinical evaluation of the MDM2-p53 antagonist RG7388 alone and in combination with chemotherapy in neuroblastoma. Oncotarget. 2015 Apr 30;6(12):10207-21.
• [6] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [7] Clinical pipeline report, company report or official report of Astex Pharmaceuticals.
• [8] Drugging the p53 pathway: understanding the route to clinical efficacy. Nat Rev Drug Discov. 2014 Mar;13(3):217-36.
• [9] Phase I clinical trail of RG7775 for treating Acute myelogenous leukemia. Roche.
• [10] Serdemetan antagonizes the Mdm2-HIF1alpha axis leading to decreased levels of glycolytic enzymes. PLoS One. 2013 Sep 6;8(9):e74741.
• [11] MDM2 inhibition: an important step forward in cancer therapy. Leukemia. 2020 Nov;34(11):2858-2874.
• [12] MI-219-zinc combination: a new paradigm in MDM2 inhibitor-based therapy. Oncogene. 2011 Jan 6;30(1):117-26.