Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMUKC5L)

• Drug Name: Tivozanib Drug Info
• Synonyms: ASP4130/AV-951

Indication

Disease Entry	ICD 11	Status	REF
Renal cell carcinoma	2C90	Approved	[1]

• Cross-matching ID:
  PubChem CID: 9911830
  ChEBI ID: CHEBI:91327
  CAS Number: CAS 475108-18-0
  TTD Drug ID: DMUKC5L

Molecule-Related Drug Atlas

Drug(s) Targeting Vascular endothelial growth factor receptor 3 (FLT-4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fruquintinib	DMHOSCQ	Colorectal cancer	2B91.Z	Approved	[2]
E-3810	DM42PFT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[3]
Sulfatinib	DMPOTM4	Neuroendocrine cancer	2B72.1	Phase 3	[4]
PI-88	DMGZPX6	Hepatocellular carcinoma	2C12.02	Phase 3	[5]
Taberminogene vadenovec	DMW5PHL	Vascular restinosis	BE2Z	Phase 3	[6]
ABT-869	DMREDYP	Solid tumour/cancer	2A00-2F9Z	Phase 3	[7]
MGCD516	DM752PU	Solid tumour/cancer	2A00-2F9Z	Phase 2/3	[8]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[9]
VATALANIB	DMY0UEQ	Solid tumour/cancer	2A00-2F9Z	Phase 2	[10]
MK-2461	DM21WBH	Alzheimer disease	8A20	Phase 1/2	[11]

Drug(s) Targeting Vascular endothelial growth factor receptor 1 (FLT-1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fruquintinib	DMHOSCQ	Colorectal cancer	2B91.Z	Approved	[2]
E-3810	DM42PFT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[3]
Sulfatinib	DMPOTM4	Neuroendocrine cancer	2B72.1	Phase 3	[4]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[9]
X-82	DMW1NKO	Age-related macular degeneration	9B75.0	Phase 2	[12]
OCV-101	DMT9QI2	Pancreatic cancer	2C10	Phase 2	[13]
LY3012212	DMRVEHY	Arteriosclerosis	BD40	Phase 2	[14]
OTSGC-A24	DMN0ZQ5	Colorectal cancer	2B91.Z	Phase 1/2	[15]
CEP-11981	DMYDTJ6	Solid tumour/cancer	2A00-2F9Z	Phase 1	[16]
EW-A-401	DM3VC6T	Peripheral vascular disease	BD4Z	Phase 1	[17]

Drug(s) Targeting Vascular endothelial growth factor receptor 2 (KDR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[18]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[19]
Regorafenib	DMHSY1I	Gastrointestinal stromal tumour	2B5B	Approved	[20]
Sunitinib	DMCBJSR	Acute undifferentiated leukemia		Approved	[21]
Axitinib	DMGVH6N	Renal cell carcinoma	2C90	Approved	[22]
Vandetanib	DMRICNP	Solid tumour/cancer	2A00-2F9Z	Approved	[23]
Pazopanib HCl	DM6U9CQ	Renal cell carcinoma	2C90	Approved	[24]
Fruquintinib	DMHOSCQ	Colorectal cancer	2B91.Z	Approved	[2]
Cabozantinib	DMIYDT4	Medullary thyroid gland carcinoma		Approved	[25]
Lenvatinib	DMB1IU4	Thyroid cancer	2D10	Approved	[26]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Vascular endothelial growth factor receptor 1 (FLT-1)	TT2Q6G1	VGFR1_HUMAN	Inhibitor	[1]
Vascular endothelial growth factor receptor 2 (KDR)	TTUTJGQ	VGFR2_HUMAN	Modulator	[1]
Vascular endothelial growth factor receptor 3 (FLT-4)	TTDCBX5	VGFR3_HUMAN	Modulator	[1]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services
• [2] Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy. Cancer Biol Ther. 2014;15(12):1635-45.
• [3] E-3810 is a potent dual inhibitor of VEGFR and FGFR that exerts antitumor activity in multiple preclinical models. Cancer Res. 2011 Feb 15;71(4):1396-405.
• [4] Clinical pipeline report, company report or official report of Hutchison Medi Pharma.
• [5] Company report (Medigen)
• [6] Advances in kinase targeting: current clinical use and clinical trials. Trends Pharmacol Sci. 2014 Nov;35(11):604-20.
• [7] Preclinical activity of ABT-869, a multitargeted receptor tyrosine kinase inhibitor. Mol Cancer Ther. 2006 Apr;5(4):995-1006.
• [8] 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: 1814).
• [9] Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients. Br J Pharmacol. 2013 Apr;168(7):1687-706.
• [10] Discovery and evaluation of 2-anilino-5-aryloxazoles as a novel class of VEGFR2 kinase inhibitors. J Med Chem. 2005 Mar 10;48(5):1610-9.
• [11] MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res. 2010 Feb 15;70(4):1524-33.
• [12] National Cancer Institute Drug Dictionary (drug id 695817).
• [13] Phase I trial of OTS11101, an anti-angiogenic vaccine targeting vascular endothelial growth factor receptor 1 in solid tumor.Cancer Sci.2013 Jan;104(1):98-104.
• [14] Icrucumab, a fully human monoclonal antibody against the vascular endothelial growth factor receptor-1, in the treatment of patients with advanced solid malignancies: a Phase 1 study. Invest New Drugs. 2014 Apr;32(2):303-11.
• [15] J Clin Oncol 33, 2015 (suppl 3; abstr 65).
• [16] 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: 8189).
• [17] DOI: http://dx.doi.org/10.1016/j.tips.2014.09.007
• [18] 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.
• [19] Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem. 2002 Dec 19;45(26):5687-93.
• [20] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [21] 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
• [22] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [23] 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.
• [24] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [25] Clinical pipeline report, company report or official report of Exelixis (2011).
• [26] Emerging drugs for ovarian cancer. Expert Opin Emerg Drugs. 2008 Sep;13(3):523-36.