CAS NO: | 475108-18-0 |
规格: | ≥98% |
包装 | 价格(元) |
2mg | 电议 |
5mg | 电议 |
10mg | 电议 |
25mg | 电议 |
50mg | 电议 |
100mg | 电议 |
250mg | 电议 |
500mg | 电议 |
Molecular Weight (MW) | 454.86 |
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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 | Tivozanib; KRN-951, AV-951; AV951; AV 951; KRN951; KRN 951 Chemical Name: 1-(2-chloro-4-((6,7-dimethoxyquinolin-4-yl)oxy)phenyl)-3-(5-methylisoxazol-3-yl)urea SMILES Code: O=C(NC1=NOC(C)=C1)NC2=CC=C(OC3=CC=NC4=CC(OC)=C(OC)C=C34)C=C2Cl |
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. Tivozanib potently inhibits VEGF-induced VEGFR2 phosphorylation in endothelial cells with IC50 of 0.16 nM. It also inhibits ligand-induced phosphorylation of PDGFRβ and c-Kit with IC50 of 1.72 and 1.63 nM, respectively. Tivozanib inhibits VEGF-mediated migration of human umbilical vein 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. |
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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. |
Effects of KRN951 on VEGFR-2 phosphorylation levels on tumor endothelium and tumor microvessel density. Cancer Res. 2006 Sep 15;66(18):9134-42. | DCE-MRI analysis of tumor vascular permeability. Athymic rats bearing Calu-6 tumors were randomized at day –1 and then treated with 0.2 mg/kg KRN951 (○), 1 mg/kg KRN951 (?), or vehicle (o) once daily for 14 days (days 0-13). Cancer Res. 2006 Sep 15;66(18):9134-42. | Effects of KRN951 on tumor vessel diameter and pericyte coverage. Cancer Res. 2006 Sep 15;66(18):9134-42. |