1. Protein Tyrosine Kinase/RTK
  2. VEGFR

Tivozanib (Synonyms: AV-951; KRN951)

Cat. No.: HY-10977 Purity: 99.52%
Handling Instructions

Tivozanib (AV-951; KRN951) is a highly potent and selective VEGFR 1/2/3 inhibitor with IC50s of 0.21, 0.16, and 0.24 nM in cell assay, respectively.

For research use only. We do not sell to patients.
Tivozanib Chemical Structure

Tivozanib Chemical Structure

CAS No. : 475108-18-0

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Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 79 In-stock
5 mg USD 72 In-stock
10 mg USD 102 In-stock
50 mg USD 288 In-stock
100 mg USD 504 In-stock
200 mg USD 900 In-stock
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  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

Tivozanib (AV-951; KRN951) is a highly potent and selective VEGFR 1/2/3 inhibitor with IC50s of 0.21, 0.16, and 0.24 nM in cell assay, respectively.

IC50 & Target

IC50: 0.21 nM (VEGFR 1), 0.16 nM (VEGFR 2), 0.24 nM (VEGFR 3)[1]

In Vitro

Tivozanib potently inhibits VEGF-induced VEGFR2 phosphorylation in endothelial cells (IC50=0.16 nM). It also inhibits ligand-induced phosphorylation of PDGFRβ and c-Kit (IC50=1.72 and 1.63 nM, respectively). Tivozanib blocks VEGF-dependent, but not VEGF-independent, activation of mitogenactivated protein kinases and proliferation of endothelial cells. It inhibits VEGF-mediated migration of human umbilical vein endothelial cells[1].

In Vivo

Following p.o. administration to athymic rats, Tivozanib decreases the microvessel density within tumor xenografts and attenuates VEGFR-2 phosphorylation levels in tumor endothelium. It also displays antitumor activity against a wide variety of human tumor xenografts, including lung, breast, colon, ovarian, pancreas, and prostate cancer[1].

Clinical Trial
References
Preparing Stock Solutions
Concentration Volume Mass 1 mg 5 mg 10 mg
1 mM 2.1985 mL 10.9924 mL 21.9848 mL
5 mM 0.4397 mL 2.1985 mL 4.3970 mL
10 mM 0.2198 mL 1.0992 mL 2.1985 mL
Please refer to the solubility information to select the appropriate solvent.
Kinase Assay

Cell-free kinase assays are done in quadruplicate with 1 μM ATP to determine the IC50 values of KRN951 against a variety of recombinant receptor and nonreceptor tyrosine kinases[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay
[1]

KRN951 is dissolved in DMSO and diluted in growth medium immediately before use[1].

Cell-based assays are done to determine the ability of KRN951 to inhibit ligand-dependent phosphorylation of receptor tyrosine kinases. Briefly, the cells are starved overnight in appropriate basic medium containing 0.5% fetal bovine serum (FBS). Following the addition of KRN951 or 0.1% DMSO, the cells are incubated for 1 hour 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 out[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

KRN951 is suspended in vehicle (0.5% methyl cellulose in distilled water[1].

Mice: Cancer cells are s.c. inoculated into the right flank of the athymic rats. Once established, tumors of 1,500 mm3 are surgically excised and smaller tumor fragments (20-30 mg) are s.c. implanted in the right flank of irradiated rats. Oral administration of KRN951 (0.2 or 1 mg/kg) or vehicle is initiated at the day of randomization (day 0). Tumor volume is measured twice weekly with Vernier calipers, and calculated[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

454.86

Formula

C₂₂H₁₉ClN₄O₅

CAS No.

475108-18-0

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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Tivozanib
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