Details of the Drug

General Information of Drug (ID: DMF5GZI)

Drug Name

RG7388

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]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 1

Molecular Weight (mw)

616.5

Topological Polar Surface Area (xlogp)

4.3

Rotatable Bond Count (rotbonds)

8

Hydrogen Bond Donor Count (hbonddonor)

3

Hydrogen Bond Acceptor Count (hbondacc)

8

Chemical Identifiers

Formula: C31H29Cl2F2N3O4
IUPAC Name: 4-[[(2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-(2,2-dimethylpropyl)pyrrolidine-2-carbonyl]amino]-3-methoxybenzoic acid
Canonical SMILES: CC(C)(C)C[C@H]1[C@]([C@H]([C@@H](N1)C(=O)NC2=C(C=C(C=C2)C(=O)O)OC)C3=C(C(=CC=C3)Cl)F)(C#N)C4=C(C=C(C=C4)Cl)F
InChI: InChI=1S/C31H29Cl2F2N3O4/c1-30(2,3)14-24-31(15-36,19-10-9-17(32)13-21(19)34)25(18-6-5-7-20(33)26(18)35)27(38-24)28(39)37-22-11-8-16(29(40)41)12-23(22)42-4/h5-13,24-25,27,38H,14H2,1-4H3,(H,37,39)(H,40,41)/t24-,25-,27+,31-/m0/s1
InChIKey: TVTXCJFHQKSQQM-LJQIRTBHSA-N

Cross-matching ID

PubChem CID: 53358942
CAS Number: 1229705-06-9
DrugBank ID: DB12325
TTD ID: D0OC4O

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]

------------------------------------------------------------------------------------

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Acute myeloid leukaemia

ICD Disease Classification

2A60

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Erbb4 tyrosine kinase receptor (Erbb-4)	DTT	ERBB4	7.08E-23	-0.51	-1.17
Ubiquitin-protein ligase E3 Mdm2 (MDM2)	DTT	MDM2	8.31E-13	0.12	0.44

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

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.