Details of the Drug

General Information of Drug (ID: DMC56T4)

• Drug Name: RAF265
• Synonyms: RAF265; 927880-90-8; CHIR-265; RAF 265; RAF-265; CHIR 265; RAF265 (CHIR-265); 1-Methyl-5-[[2-[5-(trifluoromethyl)-1h-imidazol-2-yl]-4-pyridinyl]oxy]-n-[4-(trifluoromethyl)phenyl]-1h-benzimidazol-2-amine; CHIR265; RAF265(CHIR-265); UNII-8O434L3768; 8O434L3768; 1-methyl-5-[2-[5-(trifluoromethyl)-1H-imidazol-2-yl]pyridin-4-yl]oxy-N-[4-(trifluoromethyl)phenyl]benzimidazol-2-amine; 1-Methyl-5-({2-[5-(Trifluoromethyl)-1h-Imidazol-2-Yl]pyridin-4-Yl}oxy)-N-[4-(Trifluoromethyl)phenyl]-1h-Benzimidazol-2-Amine; PubChem22594

Indication

Disease Entry	ICD 11	Status	REF
Melanoma	2C30	Phase 2	[1], [2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 3:
  Molecular Weight (mw); 518.4
  Topological Polar Surface Area (xlogp); 5.4
  Rotatable Bond Count (rotbonds); 5
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 11
• Chemical Identifiers:
  Formula: C24H16F6N6O
  IUPAC Name: 1-methyl-5-[2-[5-(trifluoromethyl)-1H-imidazol-2-yl]pyridin-4-yl]oxy-N-[4-(trifluoromethyl)phenyl]benzimidazol-2-amine
  Canonical SMILES: CN1C2=C(C=C(C=C2)OC3=CC(=NC=C3)C4=NC=C(N4)C(F)(F)F)N=C1NC5=CC=C(C=C5)C(F)(F)F
  InChI: InChI=1S/C24H16F6N6O/c1-36-19-7-6-15(10-17(19)34-22(36)33-14-4-2-13(3-5-14)23(25,26)27)37-16-8-9-31-18(11-16)21-32-12-20(35-21)24(28,29)30/h2-12H,1H3,(H,32,35)(H,33,34)
  InChIKey: YABJJWZLRMPFSI-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 11656518
  ChEBI ID: CHEBI:91451
  CAS Number: 927880-90-8
  TTD ID: D03AND

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: Melanoma
• ICD Disease Classification: 2C30

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: 5674).
• [2] ClinicalTrials.gov (NCT00304525) A Study to Evaluate RAF265, an Oral Drug Administered to Subjects With Locally Advanced or Metastatic Melanoma. U.S. National Institutes of Health.
• [3] RAF265, a dual BRAF and VEGFR2 inhibitor, prevents osteoclast formation and resorption. Therapeutic implications. Invest New Drugs. 2013 Feb;31(1):200-5.
• [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.