Biological Activity of BMS-303141

BMS-303141 is a potent ATP-citrate lyase (ACL) inhibitor with IC50 value of 0.13 uM (human recombinant ACL).
IC50 value: 0.13 uM [1]
Target: ATP citrate lyase
in vitro: In HepG2 cells, BMS-303141 showed inhibition of total lipid syntheses with an IC50 of 8 μM. A cell based Alamar Blue cytotoxicity assay was used in parallel to differentiate the effect on the inhibition of lipid synthesis versus potential cytotoxicity. Under identical incubation conditions, BMS-303141 showed no cytotoxicity up to 50 μM, indicating the observed inhibition of lipid synthesis was not a result of compound-induced cytotoxicity [1].
in vivo: In mice, BMS-303141 showed an oral bioavailability of 55% but a relatively short half-life of 2.1 h.20 We therefore decided to dose BMS-303141 admixed in the food to assure greater duration of exposure in subsequent chronic efficacy studies.There were a total of four groups in the study; mice on normal diet and high-fat diet controls, and two treated groups that were supplemented with BMS-303141 in their high-fat diet to an equivalent daily dose of 10 or 100 mg/kg. The study was continued for a total of 34 days. Food consumption and body weight gain were tracked along with weekly assessment of lipid and glucose plasma chemistries [1].

References on BMS-303141

[1]. Li JJ, et al. 2-hydroxy-N-arylbenzenesulfonamides as ATP-citrate lyase inhibitors. Bioorg Med Chem Lett. 2007 Jun 1;17(11):3208-11.
Abstract
A novel series of 2-hydroxy-N-arylbenzenesulfonamides were identified to be ATP-citrate lyase (ACL) inhibitors with compound 9 displaying potent in vitro activity (IC(50)=0.13 microM). Chronic oral dosing of compound 9 in high-fat fed mice lowered plasma cholesterol, triglyceride, and glucose, as well as inhibited weight gain.