Home Protein Tyrosine Kinase VEGFR inhibitor - c-Kit inhibitor - PDGFR inhibitor Tivozanib For research use only.

Tivozanib

Synonyms: AV-951, KRN-951

Tivozanib is a potent and selective VEGFR inhibitor for VEGFR1/2/3 with IC50 of 30 nM/6.5 nM/15 nM, and also inhibits PDGFR and c-Kit, low activity observed against FGFR-1, Flt3, c-Met, EGFR and IGF-1R. Phase 3.

Tivozanib Chemical Structure

Tivozanib Chemical Structure

CAS No. 475108-18-0

Purity & Quality Control

Tivozanib Related Products

Signaling Pathway

VEGFR Signaling Pathways

VEGFR Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
MCF7 cells Proliferation assay Antiproliferative activity against human MCF7 cells, IC50=0.38 μM 24583357
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
U-2 OS qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
Rh18 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells) 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells 29435139
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells 29435139
Click to View More Cell Line Experimental Data

Biological Activity

Description Tivozanib is a potent and selective VEGFR inhibitor for VEGFR1/2/3 with IC50 of 30 nM/6.5 nM/15 nM, and also inhibits PDGFR and c-Kit, low activity observed against FGFR-1, Flt3, c-Met, EGFR and IGF-1R. Phase 3.
Targets
VEGFR2 [1]
(Cell-free assay)		 VEGFR3 [1]
(Cell-free assay)		 EphB2 [1]
(Cell-free assay)		 VEGFR1 [1]
(Cell-free assay)		 PDGFRα [1]
(Cell-free assay)		 Click to View More Targets
6.5 nM 15 nM 24 nM 30 nM 40 nM
In vitro
In vitro AV-951 is a novel quinoline-urea derivative. AV-951 blocks VEGF-dependent activation of mitogen-activated protein kinases and proliferation of endothelial cells. [1]
Kinase Assay Kinase Assays
Cell-free kinase assays are done in quadruplicate with 1 μM ATP to determine the IC50 values of AV-951 against a variety of recombinant receptor and nonreceptor tyrosine kinases including VEGFR1, VEGFR2, VEGFR3, c-Kit, PDGFRβ, Flt-3 and FGFR1.
Cell Research Cell lines Human umbilical vein endothelial cells (HUVEC) and normal human dermal fibroblasts
Concentrations 1 μM
Incubation Time 15 minutes
Method Human umbilical vein endothelial cells (HUVEC) and normal human dermal fibroblasts-based assays are done to determine the ability of AV-951 to inhibit ligand-dependent phosphorylation of tyrosine kinase receptors. The cells are starved overnight in appropriate basic medium containing 0.5% fetal bovine serum (FBS). The cells are incubated for 1 hour following the addition of AV-951 or 0.1% DMSO, and then stimulated with the cognate ligand at 37 °C. Receptor phosphorylation is induced for 5 minutes except for VEGFR3 (10 minutes), c-Met (10 minutes), and c-Kit (15 minutes). All the ligands used in the assays are human recombinant proteins, except for VEGF-C, a rat recombinant protein. Following cell lysis, receptors are immunoprecipitated with appropriate antibodies and subjected to immunoblotting with phosphotyrosine. Quantification of the blots and calculation of IC50 values are carried ou
In Vivo
In vivo In vivo studies show that AV-951 also decreases the micro vessel density and suppresses VEGFR2 phosphorylation levels in tumor xenografts, especially at a concentration of 1mg/kg (p.o. administration). AV-951 shows almost complete inhibition of tumor xenografts growth (TGI>85%) in athymic rats. [1] Another study in rat peritoneal disseminated tumor model shows that AV-951 could prolong the survival of the tumor-bearing rats with the MST of 53.5 days. AV-951 displays antitumor activity against many human tumor xenografts including lung, breast, colon, ovarian, pancreas and prostate cancer. [2]
Animal Research Animal Models A549 xenografts in Athymic rats (RH-rnu/rnu)
Dosages 1 mg/kg
Administration Oral administration
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT04645160 Recruiting
Cholangiocarcinoma|Bile Duct Neoplasm|Biliary Tract Malignancy
National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC)
 March 4 2022 Phase 1|Phase 2
NCT03136627 Completed
Carcinoma Renal Cell
AVEO Pharmaceuticals Inc.|Bristol-Myers Squibb
 March 22 2017 Phase 1|Phase 2
NCT01853644 Completed
Recurrent Epithelial Ovarian Cancer|Recurrent Fallopian Tube Cancer|Recurrent Primary Peritoneal Cancer
Northwestern University|National Comprehensive Cancer Network
 June 6 2013 Phase 2
NCT01834183 Withdrawn
Renal Cell Carcinoma
Dana-Farber Cancer Institute
 June 2013 Phase 2
NCT01807156 Terminated
Hepatocellular Cancer
Emory University|AVEO Pharmaceuticals Inc.
 March 2013 Phase 2

Chemical Information & Solubility

Molecular Weight 454.86 Formula

C22H19ClN4O5
CAS No. 475108-18-0 SDF Download Tivozanib SDF
Smiles CC1=CC(=NO1)NC(=O)NC2=C(C=C(C=C2)OC3=C4C=C(C(=CC4=NC=C3)OC)OC)Cl
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 20 mg/mL ( (43.96 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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In vivo Formulation Calculator

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In vivo Formulation Calculator (Clear solution)

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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Frequently Asked Questions

Question 1:
Would you please provide a little bit more detail regarding how to prepare the Tivozanib for in vivo treatment and the storage condition?

Answer:
For in vivo formula, we recommend to use 2% DMSO+30% PEG 300+ddH2O up to 1mg/mL. Once dissolved it in solution, please make small aliquots and store them at -80C up to 6 months without repeated thawing and refreezing.

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