Biological Activity
BMS-309403 is a potent, selective and cell-permeable inhibitor of fatty acid binding protein 4 (FABP4) with a Ki of less than 2 nM.
In Vitro
BMS-309403 binds to FABP4 with high affinity and shows over 100-fold selectivity against FABP5 as well as the heart isoform FABP3[1]. 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[2]. 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[3].
In Vivo
A 6 week treatment with BMS-309403 improves endothelial function, phosphorylated and total eNOS and reduced plasma triglyceride levels but does not affect endothelium-independent relaxations. In cultured human microvascular endothelial cells, lipid-induced A-FABP expression is associated with reduced phosphorylated eNOS and NO production and is reversed by BMS-309403[4]. 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[2].
References & source
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.
