U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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 of TIVOZANIB

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

Molecular Formula C22H19ClN4O5
Molecular Weight 454.863
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
12.1 ng/mL
1.34 mg single, oral
dose: 1.34 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TIVOZANIB serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
14.4 ng/mL
1.34 mg single, oral
dose: 1.34 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TIVOZANIB serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
18.8 ng/mL
1.34 mg single, oral
dose: 1.34 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TIVOZANIB serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
15.9 ng/mL
1.34 mg single, oral
dose: 1.34 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TIVOZANIB serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
16.21 ng/mL
1.34 mg single, oral
dose: 1.34 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TIVOZANIB serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
21.66 ng/mL
1.34 mg single, oral
dose: 1.34 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TIVOZANIB serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
17.33 ng/mL
1.34 mg single, oral
dose: 1.34 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TIVOZANIB serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
9.293 ng/mL
0.89 mg 1 times / day multiple, oral
dose: 0.89 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TIVOZANIB serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
10.19 ng/mL
1.34 mg 1 times / day multiple, oral
dose: 1.34 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TIVOZANIB serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
17.65 ng/mL
1.78 mg 1 times / day multiple, oral
dose: 1.78 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TIVOZANIB serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
50.03 ng/mL
0.89 mg 1 times / day multiple, oral
dose: 0.89 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TIVOZANIB serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
67.46 ng/mL
1.34 mg 1 times / day multiple, oral
dose: 1.34 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TIVOZANIB serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
110 ng/mL
1.78 mg 1 times / day multiple, oral
dose: 1.78 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TIVOZANIB serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
15.51 ng/mL
1.34 mg 1 times / day multiple, oral
dose: 1.34 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TIVOZANIB serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
94.29 ng/mL
1.34 mg 1 times / day steady-state, oral
dose: 1.34 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TIVOZANIB serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1084 ng × h/mL
1.34 mg single, oral
dose: 1.34 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TIVOZANIB serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
2491 ng × h/mL
1.34 mg single, oral
dose: 1.34 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TIVOZANIB serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
2309 ng × h/mL
1.34 mg single, oral
dose: 1.34 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TIVOZANIB serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
1680 ng × h/mL
1.34 mg single, oral
dose: 1.34 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TIVOZANIB serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
1960 ng × h/mL
1.34 mg single, oral
dose: 1.34 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TIVOZANIB serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
4449 ng × h/mL
1.34 mg single, oral
dose: 1.34 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TIVOZANIB serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
6715 ng × h/mL
1.34 mg single, oral
dose: 1.34 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TIVOZANIB serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
131.2 ng × h/mL
0.89 mg 1 times / day multiple, oral
dose: 0.89 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TIVOZANIB serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
159.2 ng × h/mL
1.34 mg 1 times / day multiple, oral
dose: 1.34 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TIVOZANIB serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
274.3 ng × h/mL
1.78 mg 1 times / day multiple, oral
dose: 1.78 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TIVOZANIB serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
856 ng × h/mL
0.89 mg 1 times / day multiple, oral
dose: 0.89 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TIVOZANIB serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
1180.2 ng × h/mL
1.34 mg 1 times / day multiple, oral
dose: 1.34 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TIVOZANIB serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
1997.2 ng × h/mL
1.78 mg 1 times / day multiple, oral
dose: 1.78 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TIVOZANIB serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
258.2 ng × h/mL
1.34 mg 1 times / day multiple, oral
dose: 1.34 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TIVOZANIB serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
1640.6 ng × h/mL
1.34 mg 1 times / day steady-state, oral
dose: 1.34 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TIVOZANIB serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
89.3 h
1.34 mg single, oral
dose: 1.34 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TIVOZANIB serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
122 h
1.34 mg single, oral
dose: 1.34 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TIVOZANIB serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
121 h
1.34 mg single, oral
dose: 1.34 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TIVOZANIB serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
103 h
1.34 mg single, oral
dose: 1.34 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TIVOZANIB serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
118.7 h
1.34 mg single, oral
dose: 1.34 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TIVOZANIB serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
316.2 h
1.34 mg single, oral
dose: 1.34 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TIVOZANIB serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
577.8 h
1.34 mg single, oral
dose: 1.34 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TIVOZANIB serum
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Funbound
Doses

Doses

DosePopulationAdverse events​
2 mg 1 times / day multiple, oral
Highest studied dose
Dose: 2 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2 mg, 1 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Sources:
DLT: Hypertension, Proteinuria...
Dose limiting toxicities:
Hypertension (grade 3, 28.6%)
Proteinuria (grade 3, 14.3%)
Ataxia (grade 3, 14.3%)
Sources:
1.5 mg 1 times / day multiple, oral
MTD
Dose: 1.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1.5 mg, 1 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Sources:
DLT: Hypertension, Serum transaminase increased...
Dose limiting toxicities:
Hypertension (12.5%)
Serum transaminase increased (grade 3-4, 12.5%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Ataxia grade 3, 14.3%
DLT
2 mg 1 times / day multiple, oral
Highest studied dose
Dose: 2 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2 mg, 1 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Sources:
Proteinuria grade 3, 14.3%
DLT
2 mg 1 times / day multiple, oral
Highest studied dose
Dose: 2 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2 mg, 1 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Sources:
Hypertension grade 3, 28.6%
DLT
2 mg 1 times / day multiple, oral
Highest studied dose
Dose: 2 mg, 1 times / day
Route: oral
Route: multiple
Dose: 2 mg, 1 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Sources:
Hypertension 12.5%
DLT
1.5 mg 1 times / day multiple, oral
MTD
Dose: 1.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1.5 mg, 1 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Sources:
Serum transaminase increased grade 3-4, 12.5%
DLT
1.5 mg 1 times / day multiple, oral
MTD
Dose: 1.5 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1.5 mg, 1 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Sources:
PubMed

PubMed

TitleDatePubMed
A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery.
2013-04-15
Vascular endothelial growth factor (VEGF) receptors: drugs and new inhibitors.
2012-12-27
Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity.
2011-10-30
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.
2008-03
KRN951, a highly potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, has antitumor activities and affects functional vascular properties.
2006-09-15
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 Wed Apr 02 06:51:46 GMT 2025
Edited
by admin
on Wed Apr 02 06:51:46 GMT 2025
Record UNII
172030934T
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
KIL-8951
Preferred Name English
TIVOZANIB
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
KIL8951
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 Wed Apr 02 06:51:46 GMT 2025 , Edited by admin on Wed Apr 02 06:51:46 GMT 2025
NCI_THESAURUS C93259
Created by admin on Wed Apr 02 06:51:46 GMT 2025 , Edited by admin on Wed Apr 02 06:51:46 GMT 2025
Code System Code Type Description
RXCUI
2534233
Created by admin on Wed Apr 02 06:51:46 GMT 2025 , Edited by admin on Wed Apr 02 06:51:46 GMT 2025
PRIMARY
CAS
475108-18-0
Created by admin on Wed Apr 02 06:51:46 GMT 2025 , Edited by admin on Wed Apr 02 06:51:46 GMT 2025
PRIMARY
SMS_ID
100000134791
Created by admin on Wed Apr 02 06:51:46 GMT 2025 , Edited by admin on Wed Apr 02 06:51:46 GMT 2025
PRIMARY
DRUG BANK
DB11800
Created by admin on Wed Apr 02 06:51:46 GMT 2025 , Edited by admin on Wed Apr 02 06:51:46 GMT 2025
PRIMARY
DRUG CENTRAL
5258
Created by admin on Wed Apr 02 06:51:46 GMT 2025 , Edited by admin on Wed Apr 02 06:51:46 GMT 2025
PRIMARY
EPA CompTox
DTXSID20963865
Created by admin on Wed Apr 02 06:51:46 GMT 2025 , Edited by admin on Wed Apr 02 06:51:46 GMT 2025
PRIMARY
PUBCHEM
9911830
Created by admin on Wed Apr 02 06:51:46 GMT 2025 , Edited by admin on Wed Apr 02 06:51:46 GMT 2025
PRIMARY
USAN
ZZ-29A
Created by admin on Wed Apr 02 06:51:46 GMT 2025 , Edited by admin on Wed Apr 02 06:51:46 GMT 2025
PRIMARY
NCI_THESAURUS
C85444
Created by admin on Wed Apr 02 06:51:46 GMT 2025 , Edited by admin on Wed Apr 02 06:51:46 GMT 2025
PRIMARY
INN
9203
Created by admin on Wed Apr 02 06:51:46 GMT 2025 , Edited by admin on Wed Apr 02 06:51:46 GMT 2025
PRIMARY
ChEMBL
CHEMBL1289494
Created by admin on Wed Apr 02 06:51:46 GMT 2025 , Edited by admin on Wed Apr 02 06:51:46 GMT 2025
PRIMARY
EVMPD
SUB64411
Created by admin on Wed Apr 02 06:51:46 GMT 2025 , Edited by admin on Wed Apr 02 06:51:46 GMT 2025
PRIMARY
WIKIPEDIA
TIVOZANIB
Created by admin on Wed Apr 02 06:51:46 GMT 2025 , Edited by admin on Wed Apr 02 06:51:46 GMT 2025
PRIMARY
DAILYMED
172030934T
Created by admin on Wed Apr 02 06:51:46 GMT 2025 , Edited by admin on Wed Apr 02 06:51:46 GMT 2025
PRIMARY
FDA UNII
172030934T
Created by admin on Wed Apr 02 06:51:46 GMT 2025 , Edited by admin on Wed Apr 02 06:51:46 GMT 2025
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