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].
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