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Details

Stereochemistry ACHIRAL
Molecular Formula C22H19ClN4O5
Molecular Weight 454.8638
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TIVOZANIB

SMILES

Cc1cc(=NC(=Nc2ccc(cc2Cl)Oc3ccnc4cc(c(cc43)OC)OC)O)[nH]o1

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

Molecular Formula C22H19ClN4O5
Molecular Weight 454.8638
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: 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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions
PubMed

PubMed

TitleDatePubMed
KRN951, a highly potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, has antitumor activities and affects functional vascular properties.
2006 Sep 15
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
Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity.
2011 Oct 30
Vascular endothelial growth factor (VEGF) receptors: drugs and new inhibitors.
2012 Dec 27
A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery.
2013 Apr 15
Patents

Sample Use Guides

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
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.
Substance Class Chemical
Created
by admin
on Fri Jun 25 21:21:56 UTC 2021
Edited
by admin
on Fri Jun 25 21:21:56 UTC 2021
Record UNII
172030934T
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TIVOZANIB
INN   USAN   WHO-DD  
USAN   INN  
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
Created by admin on Fri Jun 25 21:21:56 UTC 2021 , Edited by admin on Fri Jun 25 21:21:56 UTC 2021
NCI_THESAURUS C93259
Created by admin on Fri Jun 25 21:21:56 UTC 2021 , Edited by admin on Fri Jun 25 21:21:56 UTC 2021
Code System Code Type Description
CAS
475108-18-0
Created by admin on Fri Jun 25 21:21:56 UTC 2021 , Edited by admin on Fri Jun 25 21:21:56 UTC 2021
PRIMARY
DRUG BANK
DB11800
Created by admin on Fri Jun 25 21:21:56 UTC 2021 , Edited by admin on Fri Jun 25 21:21:56 UTC 2021
PRIMARY
DRUG CENTRAL
5258
Created by admin on Fri Jun 25 21:21:56 UTC 2021 , Edited by admin on Fri Jun 25 21:21:56 UTC 2021
PRIMARY
PUBCHEM
9911830
Created by admin on Fri Jun 25 21:21:56 UTC 2021 , Edited by admin on Fri Jun 25 21:21:56 UTC 2021
PRIMARY
NCI_THESAURUS
C85444
Created by admin on Fri Jun 25 21:21:56 UTC 2021 , Edited by admin on Fri Jun 25 21:21:56 UTC 2021
PRIMARY
INN
9203
Created by admin on Fri Jun 25 21:21:56 UTC 2021 , Edited by admin on Fri Jun 25 21:21:56 UTC 2021
PRIMARY
ChEMBL
CHEMBL1289494
Created by admin on Fri Jun 25 21:21:56 UTC 2021 , Edited by admin on Fri Jun 25 21:21:56 UTC 2021
PRIMARY
EVMPD
SUB64411
Created by admin on Fri Jun 25 21:21:56 UTC 2021 , Edited by admin on Fri Jun 25 21:21:56 UTC 2021
PRIMARY
WIKIPEDIA
TIVOZANIB
Created by admin on Fri Jun 25 21:21:56 UTC 2021 , Edited by admin on Fri Jun 25 21:21:56 UTC 2021
PRIMARY
FDA UNII
172030934T
Created by admin on Fri Jun 25 21:21:56 UTC 2021 , Edited by admin on Fri Jun 25 21:21:56 UTC 2021
PRIMARY
Related Record Type Details
EXCRETED UNCHANGED
FECAL
TARGET -> INHIBITOR
IC50
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
IC50
BINDER->LIGAND
Protein binding of tivozanib is ? 99%, primarily to albumin in vitro and is independent of concentration.
TARGET -> INHIBITOR
IC50
METABOLIC ENZYME -> SUBSTRATE
MAJOR
TARGET -> INHIBITOR
IC50
METABOLIC ENZYME -> SUBSTRATE
???????????????????????????? expressed in extrahepatic tissues such as the lung and intestine, it is unlikely that this isoform would be extensively involved in generating the metabolites observed following incubations with human liver microsomes.
SALT/SOLVATE -> PARENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
blood-to-plasma ratio PHARMACOKINETIC
Tmax PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC Females had a longer estimated T1/2 (129 hours) compared to males (110 hours).
PHARMACOKINETIC