BMS-779788

A potent, highly selective partial LXR agonist with Ki of 14 nM for LXRβ, shows moderate selectivity (5-fold) over LXRα (Ki=68 nM) ; only has activity for PXR (ECU0=2 uM) in a panel of 14 NHRs; induces LXR target genes in blood in vivo (EC50=610 nM) ; increases in biliary cholesterol and decreases in phospholipid and bile acid in animal models.Atherosclerosis Phase 1 Clinical (In Vitro) :The LXR selective partial agonist BMS-779788 is identified with potent induction of ATP binding transporters ABCA1 and ABCG1 in human whole blood (EC50=1.2 μM, 55% efficacy) . (In Vivo) :BMS-779788 induces LXR target genes in blood in vivo with an EC50=610 nM, a value similar to its in vitro blood gene induction potency. BMS-779788 is 29- and 12-fold less potent than the full agonist T0901317 in elevating plasma triglyceride and LDL cholesterol, respectively, with similar results for plasma cholesteryl ester transfer protein and apolipoprotein B. In mice BMS-779788 displays peripheral induction of ABCA1 at 3 and 10 mpk doses with no significant elevation of plasma or hepatic triglycerides at these doses, showing an improved profile compared to a full pan-agonist.