Details of the Drug

General Information of Drug (ID: DMX054A)

• Drug Name: CP-547632
• Synonyms: BFF; CP 547632; CP-547,632; 3-(4-Bromo-2,6-difluorobenzyloxy)-5-(3-(4-pyrrolidin-1-ylbutyl)ureido)isothiazole-4-carboxylic acid amide

Indication

Disease Entry	ICD 11	Status	REF
Non-small-cell lung cancer	2C25.Y	Phase 2	[1], [2]
Ovarian cancer	2C73	Phase 2	[1], [2]
Solid tumour/cancer	2A00-2F9Z	Phase 2	[1], [2]

• Therapeutic Class: Anticancer Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 532.4
  Topological Polar Surface Area (xlogp); 3.7
  Rotatable Bond Count (rotbonds); 10
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 8
• Chemical Identifiers:
  Formula: C20H24BrF2N5O3S
  IUPAC Name: 3-[(4-bromo-2,6-difluorophenyl)methoxy]-5-(4-pyrrolidin-1-ylbutylcarbamoylamino)-1,2-thiazole-4-carboxamide
  Canonical SMILES: C1CCN(C1)CCCCNC(=O)NC2=C(C(=NS2)OCC3=C(C=C(C=C3F)Br)F)C(=O)N
  InChI: InChI=1S/C20H24BrF2N5O3S/c21-12-9-14(22)13(15(23)10-12)11-31-18-16(17(24)29)19(32-27-18)26-20(30)25-5-1-2-6-28-7-3-4-8-28/h9-10H,1-8,11H2,(H2,24,29)(H2,25,26,30)
  InChIKey: HXHAJRMTJXHJJZ-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 9811611
  CAS Number: 252003-65-9
  DrugBank ID: DB12962
  TTD ID: D00YPR

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	Inhibitor	[3], [4]

Molecular Expression Atlas of This Drug

• The Studied Disease: Non-small-cell lung cancer
• ICD Disease Classification: 2C25.Y

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Vascular endothelial growth factor receptor 2 (KDR)	DTT	KDR	2.74E-02	0.49	1.48

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: 7881).
• [2] ClinicalTrials.gov (NCT00096239) CP-547,632 in Treating Patients With Recurrent or Persistent Ovarian Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer. U.S. National Institutes of Health.
• [3] 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.
• [4] YM-359445, an orally bioavailable vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor, has highly potent antitumor activity against established tumors. Clin Cancer Res. 2006 Mar 1;12(5):1630-8.
• [5] 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.
• [6] Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem. 2002 Dec 19;45(26):5687-93.
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [8] 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
• [9] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [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.