TIVOZANIB

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H19ClN4O5
Molecular Weight	454.863
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC2=C(C=C1OC)C(OC3=CC(Cl)=C(NC(=O)NC4=NOC(C)=C4)C=C3)=CC=N2

InChI

InChIKey=SPMVMDHWKHCIDT-UHFFFAOYSA-N

InChI=1S/C22H19ClN4O5/c1-12-8-21(27-32-12)26-22(28)25-16-5-4-13(9-15(16)23)31-18-6-7-24-17-11-20(30-3)19(29-2)10-14(17)18/h4-11H,1-3H3,(H2,25,26,27,28)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24019545
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/23788831

Tivozanib (formerly AV-951, KRN-951) is a potent and selective VEGFR tyrosine kinase inhibitor and inhibits angiogenesis and vascular permeability in tumor tissues. It completed phase III a trial investigation for the treatment of renal cell carcinomas, but has not been still approved. In addition, this drug is in the phase II of clinical trial for the investigation it in patients with glioblastoma and colorectal carcinoma.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Vascular endothelial growth factor receptor 11 Target ID: CHEMBL2095227 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=16982756	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Renal cell carcinoma 31 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24019545	Primary	Phase III 656	Unknown Approved Use Unknown
Glioblastoma 65 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27853960	Primary	Phase II 1132	Unknown Approved Use Unknown
Colorectal cancer 101 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27401244	Primary	Phase II 1132	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
		252160391
KRN951, a highly potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, has antitumor activities and affects functional vascular properties.	2006 Sep 15	16982756
Anti-tumor activity and tumor vessel normalization by the vascular endothelial growth factor receptor tyrosine kinase inhibitor KRN951 in a rat peritoneal disseminated tumor model.	2008 Mar	18201272
Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity.	2011 Oct 30	22037377
Vascular endothelial growth factor (VEGF) receptors: drugs and new inhibitors.	2012 Dec 27	23098265
A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery.	2013 Apr 15	23398362

Patents

Sample Use Guides

In Vivo Use Guide

Advanced Renal Cell Carcinoma: 1.5 mg orally once daily. Subjects will receive 1.5 mg tivozanib once daily beginning on Day 1 for 3 weeks followed by 1 week off treatment. One cycle will be defined as 4 weeks of treatment. Cycles will be repeated every 4 weeks.

Route of Administration: Oral

In Vitro Use Guide

KRN951 (TIVOZANIB) potently inhibited VEGF-induced VEGFR-2 phosphorylation in endothelial cells at in vitro subnanomolar IC50 values (IC50 = 0.16 nmol/L). It also inhibited ligand-induced phosphorylation of platelet-derived growth factor receptor-beta (PDGFR-beta) and c-Kit (IC50 = 1.72 and 1.63 nmol/L, respectively). KRN951 blocked VEGF-dependent, but not VEGF-independent, activation of mitogen-activated protein kinases and proliferation of endothelial cells. In addition, it inhibited VEGF-mediated migration of human umbilical vein endothelial cells.

Name

Type

Language

TIVOZANIB

Official Name

English

KIL8951

Code

English

KIL-8951

Code

English

UREA, N-(2-CHLORO-4-((6,7-DIMETHOXY-4-QUINOLINYL)OXY)PHENYL)-N'-(5-METHYL-3-ISOXAZOLYL)-

Systematic Name

English

N-(2-CHLORO-4-((6,7-DIMETHOXYQUINOLIN-4-YL)OXY)PHENYL)-N'-(5-METHYLISOXAZOL-3-YL)UREA

Systematic Name

English

Tivozanib [WHO-DD]

Common Name

English

tivozanib [INN]

Common Name

English

KRN-951

Code

English

TIVOZANIB [USAN]

Common Name

English

AV-951

Code

English

Classification Tree Code System Code

WHO-ATC

L01XE34