1、Product Data SheetTivozanibCat. No.: HY-10977CAS No.: 475108-18-0分式: CHClNO分量: 454.86作靶點(diǎn): VEGFR作通路: Protein Tyrosine Kinase/RTK儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 25 mg/mL (54.96 mM; Need ultrasonic)SolventMass1 mg 5 mg 10 mgConcentration制備儲(chǔ)備液1 mM 2

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請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?6 個(gè)內(nèi)使，-20C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?1 個(gè)內(nèi)使。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍浮Ｒ韵氯芙獍付颊?qǐng)先按照 In Vitro 式配制澄清的儲(chǔ)備液，再依次添加助溶劑：為保證實(shí)驗(yàn)

3、結(jié)果的可靠性，澄 的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的式助溶1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.50 mM); Clear solution此案可獲得 2.5 mg/mL (5.50 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 400 L PE

4、G300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.50 mM); Clear solution此案可獲得 2.5 mg/mL (5.50 mM，飽和度未知) 的澄清溶液。Page 1 of 2 www.MedChemE以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄均勻。DMSO 儲(chǔ)備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合BIOLOGIC

5、AL ACTIVITY物活性 Tivozanib (AV-951; KRN951)是有效，選擇性的 VEGFR 1/2/3 抑制劑，IC50 值分別為0.21，0.16，and 0.24 nM。IC & Target VEGFR1 VEGFR2 VEGFR330 nM (IC50) 6.5 nM (IC50) 15 nM (IC50)體外研究 Tivozanib potently inhibits VEGF-induced VEGFR2 phosphorylation in endothelial cells (IC50=0.16 nM). It also inhibitsligand-ind

6、uced 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 protein kinases and proliferation ofendothelial cells. It inhibits VEGF-mediated migration of human umbilical vein endothelial cell

7、s1.體內(nèi)研究 Following p.o. administration to athymic rats, Tivozanib decreases the microvessel density within tumor xenograftsand attenuates VEGFR-2 phosphorylation levels in tumor endothelium. It also displays antitumor activity against awide variety of human tumor xenografts, including lung, breast, c

8、olon, ovarian, pancreas, and prostate cancer1.PROTOCOLKinase Assay Cell-free kinase assays are done in quadruplicate with 1 M ATP to determine the IC50 values of KRN951 against avariety of recombinant receptor and nonreceptor tyrosine kinases1.MCE has not independently confirmed the accuracy of thes

9、e methods. They are for reference only.Cell Assay 1 Cell-based assays are done to determine the ability of KRN951 to inhibit ligand-dependent phosphorylation ofreceptor tyrosine kinases. Briefly, the cells are starved overnight in appropriate basic medium containing 0.5% fetalbovine serum (FBS). Fol

10、lowing the addition of KRN951 or 0.1% DMSO, the cells are incubated for 1 hour and thenstimulated with the cognate ligand at 37C. Receptor phosphorylation is induced for 5 minutes except for VEGFR3 (10minutes), c-Met (10 minutes), and c-Kit (15 minutes). All the ligands used in the assays are human

11、recombinantproteins, except for VEGF-C, a rat recombinant protein. Following cell lysis, receptors are immunoprecipitated withappropriate antibodies and subjected to immunoblotting with phosphotyrosine. Quantification of the blots andcalculation of IC50 values are carried out1.MCE has not independen

12、tly 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 of 1,500 mm3Administration 1 are surgically excised and smaller tumor fragments (20-30 mg) are s.c. implanted in t

13、he 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). Tumorvolume is measured twice weekly with Vernier calipers, and calculated1.MCE has not independently confirmed the accuracy of these methods. They are for re

14、ference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. Technical University of Munich. 24.01.2018.Page 2 of 3 www.MedChemE Patent. US20170349880A1. Harvard Medical School LINCS LIBRARYSee more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Nakamura K, et al. KRN951, a highly potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, has antitumor activities and affectsfunctional vascular properties. Cancer Res. 2006 Sep 15;66(18):9134-42.M