产品说明书

BMS-309403

Print
Chemical Structure| 300657-03-8 同义名 : Adipocyte FABP Inhibitor;Fatty Acid Binding Protein 4 Inhibitor;FABP4 Inhibitor;aP2 Inhibitor;ALBP Inhibitor;A-FABP Inhibitor
CAS号 : 300657-03-8
货号 : A115684
分子式 : C31H26N2O3
纯度 : 99%+
分子量 : 474.55
MDL号 : MFCD09991687
存储条件：

粉末 Sealed in dry,Room Temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(221.26 mM)，配合低频超声，并水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 Adipocyte fatty acid binding protein (aFABP) is a 14.6 kDa cytosolic protein located in adipocytes and macrophages, and assists in the intracellular transport of fatty acids. It is one of a class of fatty acid binding proteins (FABPs) that are found predominately in the liver, heart, intestine, and connective tissues[5]. BMS-309403 is a potent, selective and cell-permeable inhibitor of FABP4 with a Ki of less than 2 nM, which exhibits Ki values 250 nM for FABP3 and 350 nM for FABP5[5]. BMS-309403 interacts with the fatty-acid-binding pocket within the interior of the protein and competitively inhibits the binding of endogenous fatty acids. Treatment with BMS-309403 significantly decreased MCP-1 production from THP-1 macrophages in a dose- and time-dependent manner[6]. BMS-309403 stimulates glucose uptake in C2C12 myotubes in a temporal and dose dependent manner via activation of AMP-activated protein kinase (AMPK) signaling pathway but independent of FABPs[7]. The extent of atherosclerotic lesion area in the proximal aorta is significantly reduced in the BMS-309403-treated group compared with vehicle-treated controls in both the early and late intervention studies[6]. A 6 weeks treatment with BMS-309403 improves endothelial function, phosphorylated and total eNOS (endothelial nitric oxide synthase) and reduced plasma triglyceride levels. In cultured human microvascular endothelial cells, lipid-induced aFABP expression is associated with reduced phosphorylated eNOS and NO production and is reversed by BMS-309403[8].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.11mL

0.42mL

0.21mL

10.54mL

2.11mL

1.05mL

21.07mL

4.21mL

2.11mL
参考文献

[1]Suhre K, Römisch-Margl W, et al. Identification of a potential biomarker for FABP4 inhibition: the power of lipidomics in preclinical drug testing. J Biomol Screen. 2011 Jun;16(5):467-75.

[2]Lan H, Cheng CC, et al. Small-molecule inhibitors of FABP4/5 ameliorate dyslipidemia but not insulin resistance in mice with diet-induced obesity. J Lipid Res. 2011 Apr;52(4):646-56.

[3]Mosińska P, Szczepaniak A, et al. Chain length of dietary fatty acids determines gastrointestinal motility and visceromotor function in mice in a fatty acid binding protein 4-dependent manner. Eur J Nutr. 2019 Sep 27.

[4]Okamura Y, Otani K, et al. Vasculo-protective effect of BMS-309403 is independent of its specific inhibition of fatty acid-binding protein 4. Pflugers Arch. 2017 Sep;469(9):1177-1188.

[5]Sulsky R, Magnin DR, Huang Y, Simpkins L, Taunk P, Patel M, Zhu Y, Stouch TR, Bassolino-Klimas D, Parker R, Harrity T, Stoffel R, Taylor DS, Lavoie TB, Kish K, Jacobson BL, Sheriff S, Adam LP, Ewing WR, Robl JA. Potent and selective biphenyl azole inhibitors of adipocyte fatty acid binding protein (aFABP). Bioorg Med Chem Lett. 2007 Jun 15;17(12):3511-5. doi: 10.1016/j.bmcl.2006.12.044. Epub 2006 Dec 21. PMID: 17502136.

[6]Furuhashi M, Tuncman G, Görgün CZ, Makowski L, Atsumi G, Vaillancourt E, Kono K, Babaev VR, Fazio S, Linton MF, Sulsky R, Robl JA, Parker RA, Hotamisligil GS. Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2. Nature. 2007 Jun 21;447(7147):959-65. doi: 10.1038/nature05844. Epub 2007 Jun 6. PMID: 17554340; PMCID: PMC4076119.

[7]Lin W, Huang X, Zhang L, Chen D, Wang D, Peng Q, Xu L, Li J, Liu X, Li K, Ding K, Jin S, Li J, Wu D. BMS309403 stimulates glucose uptake in myotubes through activation of AMP-activated protein kinase. PLoS One. 2012;7(8):e44570. doi: 10.1371/journal.pone.0044570. Epub 2012 Aug 31. PMID: 22952994; PMCID: PMC3432117.

[8]Lee MY, Li H, Xiao Y, Zhou Z, Xu A, Vanhoutte PM. Chronic administration of BMS309403 improves endothelial function in apolipoprotein E-deficient mice and in cultured human endothelial cells. Br J Pharmacol. 2011 Apr;162(7):1564-76. doi: 10.1111/j.1476-5381.2010.01158.x. PMID: 21175571; PMCID: PMC3057294.