Brivanib-alaninate-BMS-582664-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEBrivanib alaninateCat. No.: HY-10336CAS No.: 649735-63-7Synonyms: BMS-582664分式: CHFNO分量: 441.46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 mont

2、h溶解性数据体外实验 DMSO : 125 mg/mL (283.15 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.2652 mL 11.3261 mL 22.6521 mL5 mM 0.4530 mL 2.2652 mL 4.5304 mL10 mM 0.2265 mL 1.1326 mL 2.2652 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。BIOLOGICAL ACTIVITY物活性 Bri

3、vanib alaninate种ATP竞争性的 VEGFR2 抑制剂，IC50 值为 25 nM；可以适度抑制 VEGFR1 和FGFR1，对 VEGFR2 的选择性是对 PDGFR的 240 倍。IC50 & Target VEGFR225 nM (IC50)1/3 Master of Small Molecules 您边的抑制剂师www.MedChemE体外研究 Brivanib inhibits VEGFR1 and FGFR-1 with IC50 of 0.38 M and 0.148 M. Brivanib is not sensitive toPDGFR, EGFR, LCK,

4、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 low activity to tumor cell lines 1. Brivanib doses 20 M paradoxicallyenhances FGF-induced L

5、X-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 activation, and is possibly through inhibition of PDGF-BB-induced stellate cell activation 3.体内研究

6、 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,brivanib significantly suppresses tumor growth in Hepatocellular carcinoma (HCC) xenografts

7、, 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. Brivanib issuggested to be efficient in treatment of HCC 2. Brivanib (50 mg/kg, p.o.) attenuates

8、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 ligated animals 3.PROTOCOLCell Assay 3 Viability is measured in LX-2 cells using the Cell Count

9、ing 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 is added at different doses. Two hours later, 5 ng/mLPDGF-BB is added. The cells are incub

10、ated for an additional 72 hours and cell viability is measured. Eachexperiment is performed in three replicates at least four times 3.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Male mice 4-6 weeks of age are treated 3 times a week with a tot

11、al 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. The animals are sacrificed 4 weeks after the start of the injections3.MCE has not independ

12、ently confirmed the accuracy of these methods. They 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. Harvard Medical School LINCS LIBRARYSee more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Bhide RS, et al. Discovery and preclinical studies of (

13、R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5- methylpyrrolo2,1-f1,2,4triazin-6-2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEyloxy)propan- 2-ol (BMS-540215), an in vivo active potent VEGFR-2 inhibitor. J Med Chem, 2006, 49 (7), 2143-2146.2. Huynh H, et al. Brivanib alaninate, a dual inhibitor o

14、f 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, 14(19), 6146-6153.3. 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 One. 2015 Nov 3;10