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
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 616.5
  Logarithm of the Partition Coefficient (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
  ChEBI ID: CHEMBL2402737
  CAS Number: 1229705-06-9
  UNII: QSQ883V35U
  DrugBank ID: DB12325
  TTD ID: D0OC4O
• Drug-Molecule Activity Atlas (DMA)NEW: Click to Jump to the Detailed DMA Information of This Drug
• Drug Pharmacogenomic Perturbation (DPP)NEW: Click to Jump to the Detailed DPP Information of This Drug
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

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 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

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.