product name Tivozanib (KRN-951)
Description: Tivozanib, also known as KRN951 or AV-951, is an orally bioavailable, potent and selective VEGFR inhibitor for VEGFR1/2/3 with IC50 of 30 nM/6.5 nM/15 nM. Tivozanib binds to and inhibits VEGFRs 1, 2 and 3, which may result in the inhibition of endothelial cell migration and proliferation, inhibition of tumor angiogenesis and tumor cell death.
References: Cancer Res. 2006 Sep 15;66(18):9134-42; Cancer Sci. 2008 Mar;99(3):623-30.
454.86
Formula
C22H19ClN4O5
CAS No.
475108-18-0
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 20 mg/mL (43.96 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
0.5% methylcellulose: 30 mg/mL
Synonyms
KRN-951, AV-951
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19401897
| In Vitro |
In vitro activity: Tivozanib (AV-951) is a novel quinoline-urea derivative. AV-951 blocks VEGF-dependent activation of mitogen-activated protein kinases and proliferation of endothelial cells. Kinase Assay: 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 Assay: 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 out. |
|---|---|
| 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. 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. |
| Animal model | A549 xenografts in Athymic rats (RH-rnu/rnu) |
| Formulation & Dosage | Formulated in 0.5% methylcellulose in distilled water; 1mg/kg; oral gavage |
| References | Cancer Res. 2006 Sep 15;66(18):9134-42; Cancer Sci. 2008 Mar;99(3):623-30. |
Related Posts
product name Tivozanib (KRN-951)
Description: Tivozanib, also known as KRN951 or AV-951, is an orally bioavailable, potent and selective VEGFR inhibitor for VEGFR1/2/3 with IC50 of 30 nM/6.5 nM/15 nM. Tivozanib binds to and inhibits VEGFRs 1, 2 and 3, which may result in the inhibition of endothelial cell migration and proliferation, inhibition of tumor angiogenesis and tumor cell death.
References: Cancer Res. 2006 Sep 15;66(18):9134-42; Cancer Sci. 2008 Mar;99(3):623-30.
454.86
Formula
C22H19ClN4O5
CAS No.
475108-18-0
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 20 mg/mL (43.96 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
0.5% methylcellulose: 30 mg/mL
Synonyms
KRN-951, AV-951
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19401897
| In Vitro |
In vitro activity: Tivozanib (AV-951) is a novel quinoline-urea derivative. AV-951 blocks VEGF-dependent activation of mitogen-activated protein kinases and proliferation of endothelial cells. Kinase Assay: 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 Assay: 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 out. |
|---|---|
| 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. 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. |
| Animal model | A549 xenografts in Athymic rats (RH-rnu/rnu) |
| Formulation & Dosage | Formulated in 0.5% methylcellulose in distilled water; 1mg/kg; oral gavage |
| References | Cancer Res. 2006 Sep 15;66(18):9134-42; Cancer Sci. 2008 Mar;99(3):623-30. |