BMS-309403 - FABP4 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEBMS-309403Cat. No.: HY-101903CAS No.: 300657-03-8分式: CHNO分量: 474.55作靶點(diǎn): FABP作通路: Metabolic Enzyme/Protease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 : 62.5 mg/mL (131.70 mM)H2O : 40% PEG

2、300 5% Tween-80 45% salineSolubility: 2.08 mg/mL (4.38 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.08 mg/mL (4.38 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEBIOLOGICAL ACTIVITY物活性 BMS-309403有效，選擇和可滲透細(xì)胞的脂 酸結(jié)合蛋 (aFABP) 抑制劑，其Ki值于 2 nM。IC50 & Target Ki: l

3、ess than 2 nM (FABP4), 250 nM (FABP3), 350 nM (FABP5) 1體外研究 BMS-309403 binds to FABP4 with high affinity and shows over 100-fold selectivity against FABP5 as well asthe heart isoform FABP3 1. BMS-309403 interacts with the fatty-acid-binding pocket within the interior of theprotein and competitively

4、inhibits the binding of endogenous fatty acids. Treatment with BMS-309403significantly decreased MCP-1 production from THP-1 macrophages in a dose- and time-dependent manner2. BMS-309403 stimulates glucose uptake in C2C12 myotubes in a temporal and dose dependent mannervia activation of AMP-activate

5、d protein kinase (AMPK) signaling pathway but independent of FABPs 3.體內(nèi)研究 A 6 week treatment with BMS-309403 improves endothelial function, phosphorylated and total eNOS andreduced plasma triglyceride levels but does not affect endothelium-independent relaxations. In culturedhuman microvascular endo

6、thelial cells, lipid-induced A-FABP expression is associated with reducedphosphorylated eNOS and NO production and is reversed by BMS-309403 4. The extent of atheroscleroticlesion area in the proximal aorta is significantly reduced in the BMS-309403-treated group compared withvehicle-treated control

7、s in both the early and late intervention studies 2.PROTOCOLAnimal Mice: To determine the effects of pharmacological inhibition of the actions of A-FABP, either the A-FABPAdministration 4 inhibitor BMS-309403 (15 mg/kg) or vehicle (4% Tween 80) are administered chronically by daily oral gavagefor 6

8、weeks in ApoE/ mice (starting at weeks 12 of age). Mice are anaesthetized with a bolus injection ofpentobarbitone sodium (230 mg/kg) and their aorta removed and dissected for further analysis 4.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶(hù)使本產(chǎn)品發(fā)表的科研獻(xiàn)

9、 Cell Death Dis. 2019 May 16;10(6):382. Parasitol Res. 2019 Jun;118(6):1919-1926.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Sulsky R, et al. Potent and selective biphenyl azole inhibitors of adipocyte fatty acid binding protein (aFABP). Bioorg Med Chem Lett.2007 Jun 15;17(

10、12):3511-5.2. Furuhashi M, et al. Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2. Nature. 2007 Jun21;447(7147):959-65.3. Lin W, et al. BMS309403 stimulates glucose uptake in myotubes through activation of AMP-activated protein kinase. PLoS One.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE2012;7(8):e44570.4. Lee MY, et al. Chronic administration of BMS309403 improves endothelial function in apolipoprotein E-deficient mice and in culturedhuman endothelial cells. Br J Pharmacol. 2011 Apr;162(7):1564-76.McePdfHeightCaution: Product has not be