Brivanib-BMS-540215-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEBrivanibCat. No.: HY-10337CAS No.: 649735-46-6Synonyms: BMS-540215分式: CHFNO分量: 370.38作靶点: VEGFR; Autophagy作通路: Protein Tyrosine Kinase/RTK; Autophagy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

2、 DMSO : 50 mg/mL (135.00 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.6999 mL 13.4996 mL 26.9993 mL5 mM 0.5400 mL 2.6999 mL 5.3999 mL10 mM 0.2700 mL 1.3500 mL 2.6999 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

3、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，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 (6.75 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 (6.75 mM); Clear solution1/3 Master

4、of Small Molecules 您边的抑制剂师www.MedChemE3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (6.75 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Brivanib种ATP竞争性的 VEGFR2 抑制剂，IC50 值为 25 nM；可以适度抑制 VEGFR-1 和 FGFR-1，对VEGFR2 的选择性是对 PDGFR- 的 240 倍。IC50 & Target VEGFR225 nM (IC50)体外研究 Brivanib inhibits VEGFR1

5、 and FGFR-1 with IC50 of 0.38 M and 0.148 M. Brivanib is not sensitive toPDGFR, EGFR, LCK, PKC or JAK-3 with IC50 all above 1900 nM. Brivanib could inhibit the proliferation ofVEGF-stimulated HUVECs with IC50 of 40 nM, compared to 276 nM in FGF-stimulated HUVECs. On theother hand, brivanib exhibits

6、low activity to tumor cell lines 1. Brivanib doses 20 M paradoxicallyenhances FGF-induced LX-2 cell proliferation, whereas higher brivanib doses (30 M) inhibits LX-2 cellproliferation. The inhibitory effect of brivanib on liver fibrosis is not through inhibition of TGF-1-inducedstellate cell activat

7、ion, and is possibly through inhibition of PDGF-BB-induced stellate cell activation 3.体内研究 Brivanib displays antitumor activities in H3396 xenograft in athymic mice. At a dose of 60 and 90 mg/kg(p.o.), brivanib completely inhibits the tumor growth, with TGI of 85% and 97%, respectively 1. Moreover,b

8、rivanib significantly suppresses tumor growth in Hepatocellular carcinoma (HCC) xenografts, which due tothe decrease in phosphorylation of VEGFR2. The results show that the tumor weights in 06-0606 xenograftmice are 55% and 13%, compared with the controls at a dose of 50 mg/kg and 100 mg/kg. Brivani

9、b issuggested to be efficient in treatment of HCC 2. Brivanib (50 mg/kg, p.o.) attenuates liver fibrosis andstellate cell activation induced by BDL in mice. Brivanib inhibits growth factor and growth factor receptormRNA expression in sham control animals but shows variable effects in bile duct ligat

10、ed animals 3.PROTOCOLCell Assay 3 Viability is measured in LX-2 cells using the Cell Counting Kit-8 (CCK-8). Using 96-well plates with 2,000cells per well, HSCs are incubated in 10% FBS-supplemented DMEM for 24 hours, followed by starvation inserum-free media. After 24 hours of starvation, brivanib

11、is added at different doses. Two hours later, 5 ng/mLPDGF-BB is added. The cells are incubated for an additional 72 hours and cell viability is measured. Eachexperiment is performed in three replicates at least four times.MCE has not independently confirmed the accuracy of these methods. They are fo

12、r reference only.Animal Male mice 4-6 weeks of age are treated 3 times a week with a total of 12 intraperitoneal (i.p.) injections ofAdministration 3 150 mL/kg TAA. At the onset of TAA treatment, placebo or brivanib (25 or 50 mg/kg) is administered orally on5 consecutive days with weekend breaks. Th

13、e animals are sacrificed 4 weeks after the start of the injections.MCE has not independently confirmed the accuracy of these methods. They are for reference only.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemE户使本产品发表的科研献 Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. Harvard Medical School LI

14、NCS LIBRARYSee more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Bhide RS, et al. Discovery and preclinical studies of (R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5- methylpyrrolo2,1-f1,2,4triazin-6-yloxy)propan- 2-ol (BMS-540215), an in vivo active potent VEGFR-2 inhibitor. J Med

15、Chem, 2006, 49 (7), 2143-2146.2. Huynh H, et al. Brivanib alaninate, a dual inhibitor of vascular endothelial growth factor receptor and fibroblast growth factor receptortyrosine kinases, induces growth inhibition in mouse models of human hepatocellular carcinoma. Clin Cancer Res, 2008,3. Nakamura I, et al. Correction: Brivanib Attenuates Hepatic Fibrosis In Vivo and Stellate Cell Activation In Vitro by Inhibition of FGF,VEGF and PDGF Signaling. PLoS