Details of the Drug

General Information of Drug (ID: DMDOCNW)

• Drug Name: E-7050
• Synonyms: C-Met and VEGF-2 tyrosine kinase inhibitor (oral, cancer), Eisai

Indication

Disease Entry	ICD 11	Status	REF
Head and neck cancer	2D42	Phase 1	[1], [2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 633.7
  Topological Polar Surface Area (xlogp); 4.1
  Rotatable Bond Count (rotbonds); 8
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 9
• Chemical Identifiers:
  Formula: C33H37F2N7O4
  IUPAC Name: 1-N'-[2-fluoro-4-[2-[[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]amino]pyridin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
  Canonical SMILES: CN1CCN(CC1)C2CCN(CC2)C(=O)NC3=NC=CC(=C3)OC4=CC(=C(C=C4)NC(=O)C5(CC5)C(=O)NC6=CC=C(C=C6)F)F
  InChI: InChI=1S/C33H37F2N7O4/c1-40-16-18-41(19-17-40)24-9-14-42(15-10-24)32(45)39-29-21-26(8-13-36-29)46-25-6-7-28(27(35)20-25)38-31(44)33(11-12-33)30(43)37-23-4-2-22(34)3-5-23/h2-8,13,20-21,24H,9-12,14-19H2,1H3,(H,37,43)(H,38,44)(H,36,39,45)
  InChIKey: UQRCJCNVNUFYDX-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 16118392
  CAS Number: 928037-13-2
  DrugBank ID: DB11977
  TTD ID: D09ETH

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Proto-oncogene c-Met (MET)	TTNDSF4	MET_HUMAN	Modulator	[3]
Vascular endothelial growth factor receptor 2 (KDR)	TTUTJGQ	VGFR2_HUMAN	Modulator	[3]

Molecular Expression Atlas of This Drug

• The Studied Disease: Head and neck cancer
• ICD Disease Classification: 2D42

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
Proto-oncogene c-Met (MET)	DTT	MET	1.08E-03	-0.24	-0.4

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: 7956).
• [2] ClinicalTrials.gov (NCT02533102) Pharmacokinetics and Food Effect of Single Oral Dose of E7050 in Healthy Volunteers.
• [3] E7050: a dual c-Met and VEGFR-2 tyrosine kinase inhibitor promotes tumor regression and prolongs survival in mouse xenograft models. Cancer Sci. 2010 Jan;101(1):210-5.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [5] Clinical pipeline report, company report or official report of Exelixis (2011).
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
• [8] Antitumor Activity of Amivantamab (JNJ-61186372), an EGFR-MET Bispecific Antibody, in Diverse Models of EGFR Exon 20 Insertion-Driven NSCLC. Cancer Discov. 2020 Aug;10(8):1194-1209.
• [9] 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: 1815).
• [10] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [11] Beperminogene perplasmid for the treatment of critical limb ischemia. Expert Rev Cardiovasc Ther. 2014 Oct;12(10):1145-56.
• [12] 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: 7948).
• [13] 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.
• [14] Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem. 2002 Dec 19;45(26):5687-93.
• [15] 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
• [16] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [17] 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.
• [18] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [19] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services
• [20] Emerging drugs for ovarian cancer. Expert Opin Emerg Drugs. 2008 Sep;13(3):523-36.