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

General Information of Drug (ID: DMF5GZI)

• Drug Name: RG7388 Drug Info
• Synonyms: Idasanutlin; RG7388; 1229705-06-9; Idasanutlin (RG-7388); RG-7388; UNII-QSQ883V35U; QSQ883V35U; CHEMBL2402737; Benzoic acid, 4-((((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-(2,2-dimethylpropyl)-2-pyrrolidinyl)carbonyl)amino)-3-methoxy-; RO5503781; Idasanutlin [USAN:INN]; Benzoic acid, 4-[[[(2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-(2,2-dimethylpropyl)-2-pyrrolidinyl]carbonyl]amino]-3-methoxy-; RG-7388;Idasanutlin; RO-5503781; SCHEMBL442856

Indication

Disease Entry	ICD 11	Status	REF
Acute myeloid leukaemia	2A60	Phase 3	[1]
Solid tumour/cancer	2A00-2F9Z	Phase 3	[2]
Polycythemia vera	2A20.4	Phase 2	[3]
Haematological malignancy	2B33.Y	Phase 1	[4]

• Cross-matching ID:
  PubChem CID: 53358942
  CAS Number: CAS 1229705-06-9
  TTD Drug ID: DMF5GZI

Molecule-Related Drug Atlas

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
APG-115	DMIFA0L	Prolymphocytic leukaemia	2A82.1	Phase 2	[3]
ALRN-6924	DMLBWT1	Haematological malignancy	2B33.Y	Phase 2	[3]
AMG 232	DM65PTO	Merkel cell carcinoma	2C34	Phase 2	[7]
ASTX295	DM9EM5G	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[8]
HDM201	DMVRTCW	Haematological malignancy	2B33.Y	Phase 1	[3]
DS-3032	DMA2B5Y	Haematological malignancy	2B33.Y	Phase 1	[9]
RG7775	DMXBS6U	Acute myeloid leukaemia	2A60	Phase 1	[10]
JNJ-26854165	DMNSJ3C	Non-small-cell lung cancer	2C25.Y	Phase 1	[11]
BI 907828	DM2Z4YQ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[12]
MI-219	DM196LK	Triple negative breast cancer	2C60-2C65	Investigative	[13]

Drug(s) Targeting Erbb4 tyrosine kinase receptor (Erbb-4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dacomitinib	DMOH8VY	Non-small-cell lung cancer	2C25.Y	Approved	[14]
CI-1033	DMSI8N3	Lymphoma	2A80-2A86	Phase 2	[15]
JI-101	DMM02VJ	Solid tumour/cancer	2A00-2F9Z	Phase 2	[16]
JNJ-26483327	DMSQ3AZ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[17]
PMID24915291C38	DMBXT9J	Discovery agent	N.A.	Investigative	[18]
HDS-029	DMLRUVA	Discovery agent	N.A.	Investigative	[19]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Erbb4 tyrosine kinase receptor (Erbb-4)	TT0JESD	ERBB4_HUMAN	Inhibitor	[5]
Ubiquitin-protein ligase E3 Mdm2 (MDM2)	TT08GJW	MDM2_HUMAN	Modulator	[6]

References

• [1] ClinicalTrials.gov (NCT02545283) A Study of Idasanutlin With Cytarabine Versus Cytarabine Plus Placebo in Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML) (MIRROS). U.S. National Institutes of Health.
• [2] Small molecules, big targets: drug discovery faces the protein-protein interaction challenge.Nat Rev Drug Discov. 2016 Aug;15(8):533-50.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] ClinicalTrials.gov (NCT02407080) Open Label Study of Single Agent Oral RG7388 in Patients With Polycythemia Vera and Essential Thrombocythemia. U.S. National Institutes of Health.
• [5] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1799).
• [6] 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.
• [7] Discovery of a small molecule MDM2 inhibitor (AMG 232) for treating cancer. J Med Chem. 2014 Aug 14;57(15):6332-41.
• [8] Clinical pipeline report, company report or official report of Astex Pharmaceuticals.
• [9] Drugging the p53 pathway: understanding the route to clinical efficacy. Nat Rev Drug Discov. 2014 Mar;13(3):217-36.
• [10] Phase I clinical trail of RG7775 for treating Acute myelogenous leukemia. Roche.
• [11] Serdemetan antagonizes the Mdm2-HIF1alpha axis leading to decreased levels of glycolytic enzymes. PLoS One. 2013 Sep 6;8(9):e74741.
• [12] MDM2 inhibition: an important step forward in cancer therapy. Leukemia. 2020 Nov;34(11):2858-2874.
• [13] MI-219-zinc combination: a new paradigm in MDM2 inhibitor-based therapy. Oncogene. 2011 Jan 6;30(1):117-26.
• [14] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7422).
• [15] A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
• [16] A pilot study of JI-101, an inhibitor of VEGFR-2, PDGFR-, and EphB4 receptors, in combination with everolimus and as a single agent in an ovarian cancer expansion cohort.Invest New Drugs.2015 Dec;33(6):1217-24.
• [17] National Cancer Institute Drug Dictionary (drug id 596693).
• [18] Discovery of a series of 2,5-diaminopyrimidine covalent irreversible inhibitors of Bruton's tyrosine kinase with in vivo antitumor activity. J Med Chem. 2014 Jun 26;57(12):5112-28.
• [19] Tyrosine kinase inhibitors. 19. 6-Alkynamides of 4-anilinoquinazolines and 4-anilinopyrido[3,4-d]pyrimidines as irreversible inhibitors of the erbB... J Med Chem. 2006 Feb 23;49(4):1475-85.