Details of the Drug

General Information of Drug (ID: DM942HP)

• Drug Name: Brivanib
• Synonyms: Brivanib; 649735-46-6; BMS-540215; Brivanib (BMS-540215); BMS 540215; UNII-DDU33B674I; Brivanib [USAN]; BMS540215; DDU33B674I; CHEMBL377300; (2R)-1-[4-(4-Fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy]propanol; Brivanib (USAN); (2R)-1-[4-[(4-FLUORO-2-METHYL-1H-INDOL-5-YL)OXY]-5-METHYL-PYRROLO[2,1-F][1,2,4]TRIAZIN-6-YL]OXYPROPAN-2-OL; (2R)-1-({4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl}oxy)propan-2-ol

Indication

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Phase 3	[1], [2]
Liver cancer	2C12	Phase 3	[1], [2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 370.4
  Topological Polar Surface Area (xlogp); 3
  Rotatable Bond Count (rotbonds); 5
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 6
• Chemical Identifiers:
  Formula: C19H19FN4O3
  IUPAC Name: (2R)-1-[4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl]oxypropan-2-ol
  Canonical SMILES: CC1=CC2=C(N1)C=CC(=C2F)OC3=NC=NN4C3=C(C(=C4)OC[C@@H](C)O)C
  InChI: InChI=1S/C19H19FN4O3/c1-10-6-13-14(23-10)4-5-15(17(13)20)27-19-18-12(3)16(26-8-11(2)25)7-24(18)22-9-21-19/h4-7,9,11,23,25H,8H2,1-3H3/t11-/m1/s1
  InChIKey: WCWUXEGQKLTGDX-LLVKDONJSA-N
• Cross-matching ID:
  PubChem CID: 11234052
  ChEBI ID: CHEBI:94562
  CAS Number: 649735-46-6
  DrugBank ID: DB11958
  TTD ID: D0HS5V

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Vascular endothelial growth factor receptor 2 (KDR)	TTUTJGQ	VGFR2_HUMAN	Modulator	[3]

Molecular Expression Atlas of This Drug

• The Studied Disease: Breast cancer
• ICD Disease Classification: 2C60-2C65

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Vascular endothelial growth factor receptor 2 (KDR)	DTT	KDR	1.98E-01	0.11	0.2

References

• [1] 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: 5671).
• [2] ClinicalTrials.gov (NCT01108705) Comparison of Brivanib and Best Supportive Care (BSC) With Placebo and BSC for Treatment of Liver Cancer in Asian Patients Who Have Failed Sorafenib Treatment. U.S. National Institutes of Health.
• [3] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [4] Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling.Mol Cancer Ther.2008 Oct;7(10):3129-40.
• [5] Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem. 2002 Dec 19;45(26):5687-93.
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [7] 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
• [8] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [9] 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.
• [10] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [11] Clinical pipeline report, company report or official report of Exelixis (2011).
• [12] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services
• [13] Emerging drugs for ovarian cancer. Expert Opin Emerg Drugs. 2008 Sep;13(3):523-36.