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. 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.

 Zotarolimus A179578 ABT 578

 Zonisamide sodium salt

 ZM323881

 Zibotentan

 ZM 241385