Tivozanib-AV-951-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemETivozanibCat. No.: HY-10977CAS No.: 475108-18-0Synonyms: AV-951; KRN951分式: CHClNO分量: 454.86作靶点: VEGFR作通路: Protein Tyrosine Kinase/RTK储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 25 mg/mL

2、 (54.96 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.1985 mL 10.9924 mL 21.9848 mL5 mM 0.4397 mL 2.1985 mL 4.3970 mL10 mM 0.2198 mL 1.0992 mL 2.1985 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验 请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，

3、当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.50 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.50 mM); Clear solution1/3 Master of Small Molecules 您边的抑制剂师www.MedChemEB

4、IOLOGICAL ACTIVITY物活性 Tivozanib (AV-951; KRN951)是有效，选择性的 VEGFR 1/2/3 抑制剂，IC50 值分别为0.21，0.16，and 0.24nM。IC50 & Target VEGFR1 VEGFR2 VEGFR330 nM (IC50) 6.5 nM (IC50) 15 nM (IC50)体外研究 Tivozanib potently inhibits VEGF-induced VEGFR2 phosphorylation in endothelial cells (IC50=0.16 nM). Italso inhibits li

5、gand-induced phosphorylation of PDGFR and c-Kit (IC50=1.72 and 1.63 nM, respectively).Tivozanib blocks VEGF-dependent, but not VEGF-independent, activation of mitogenactivated proteinkinases and proliferation of endothelial cells. It inhibits VEGF-mediated migration of human umbilical veinendothelia

6、l cells 1.体内研究 Following p.o. administration to athymic rats, Tivozanib decreases the microvessel density within tumorxenografts and attenuates VEGFR-2 phosphorylation levels in tumor endothelium. It also displays antitumoractivity against a wide variety of human tumor xenografts, including lung, br

7、east, colon, ovarian, pancreas,and prostate cancer 1.PROTOCOLKinase Assay Cell-free kinase assays are done in quadruplicate with 1 M ATP to determine the IC50 values of KRN951against a variety of recombinant receptor and nonreceptor tyrosine kinases 1.MCE has not independently confirmed the accuracy

8、 of these methods. They are for reference only.Cell Assay 1 Cell-based assays are done to determine the ability of KRN951 to inhibit ligand-dependent phosphorylationof receptor tyrosine kinases. Briefly, the cells are starved overnight in appropriate basic medium containing0.5% fetal bovine serum (F

9、BS). Following the addition of KRN951 or 0.1% DMSO, the cells are incubated for1 hour and then stimulated with the cognate ligand at 37C. Receptor phosphorylation is induced for 5minutes except for VEGFR3 (10 minutes), c-Met (10 minutes), and c-Kit (15 minutes). All the ligands used inthe assays are

10、 human recombinant proteins, except for VEGF-C, a rat recombinant protein. Following celllysis, receptors are immunoprecipitated with appropriate antibodies and subjected to immunoblotting withphosphotyrosine. Quantification of the blots and calculation of IC50 values are carried out 1.MCE has not i

11、ndependently confirmed the accuracy of these methods. They are for reference only.Animal Mice: Cancer cells are s.c. inoculated into the right flank of the athymic rats. Once established, tumors ofAdministration 1 1,500 mm3 are surgically excised and smaller tumor fragments (20-30 mg) are s.c. impla

12、nted in the rightflank of irradiated rats. Oral administration of KRN951 (0.2 or 1 mg/kg) or vehicle is initiated at the day ofrandomization (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

13、are for reference only.户使本产品发表的科研献 Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemE Technical University of Munich. 24.01.2018. Patent. US20170349880A1. Harvard Medical School LINCS LIBRARYSee more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Nakamura K, et al. KRN951, a highly potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, has antitumoractivities and affects functional vascular properties. Cancer Res. 2006 Sep 15;66(18):913