Background:

BMS-303141 is a potent inhibitor of ATP-citrate lyase with IC50 value of 0.13 μM [1].

ATP-citrate lyase (ACL) is a cytosolic enzyme that responsible for the production of cytosolic acetyl-CoA, a precursor required for de novo biosyntheses of cholesterol and fatty acids. Inhibition of ACL is used to treat dyslipidemia and obesity [1].

BMS-303141 is a potent ATP-citrate lyase inhibitor. In HepG2 cells, BMS-303141 inhibited total lipid syntheses with IC50 value of 8 μM. Also, BMS-303141 showed no cytotoxicity up to 50 μM [1].

In mice, BMS-303141 exhibited an oral bioavailability of 55%. In high-fat fed mice, BMS-303141 reduced the levels of plasma triglyceride, cholesterol by 20-30% and glucose by 30-50% and inhibited weight gain [1]. BMS-303141 inhibited ACL with IC50 value of 0.94 μM for human ACL in a concentration dependant way [2].

参考文献:
[1].  Li JJ, Wang H, Tino JA, et al. 2-hydroxy-N-arylbenzenesulfonamides as ATP-citrate lyase inhibitors. Bioorg Med Chem Lett, 2007, 17(11): 3208-3211.
[2].  Ma Z, Chu CH, Cheng D. A novel direct homogeneous assay for ATP citrate lyase. J Lipid Res, 2009, 50(10): 2131-2135.