BMS-779788

BMS-779788 is a LXR partial agonist with IC50 values of 68 nM for LXRα and 14 nM for LXRβ.

Signaling Pathways >> Metabolic Enzyme/Protease >> LXR

Research Areas >> Metabolic Disease

IC50: 68 nM (LXRα); 14 nM (LXRβ)[1]

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)[2].

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[1]. 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[2].

Monkeys: Male cynomolgus monkeys are used in the study. For a single-dose pharmacokinetic (PK)-pharmacodynamic (PD) study, 2 animals each are treated either with vehicle [0.5% carboxymethyl cellulose and 2% Tween 80 in purified water) or 1 mg/kg BMS-779788. For the 7 day PD study, 18 animals are randomized into 6 treatment groups (N=3/group; 3-6 kg) and received the following treatments at 7 AM daily for 7 days by oral gavage: vehicle, 10 mg/kg per day T0901317 and 0.3, 1, 3, or 10 mg/kg per day BMS-779788[1].

[1]. Kirchgessner TG, et al. Pharmacological characterization of a novel liver X receptor agonist with partial LXRα activity and a favorable window in nonhuman primates. J Pharmacol Exp Ther. 2015 Feb;352(2):305-14.

[2]. Kick E, et al. Liver X receptor (LXR) partial agonists: biaryl pyrazoles and imidazoles displaying a preference for LXRβ. Bioorg Med Chem Lett. 2015 Jan 15;25(2):372-7.

T0901317 | GW3965 HCl | WAY 252623 | SR 9243 | (20S)-Protopanaxatriol | 27-Hydroxycholesterol | GSK 2033 | AZ876 | SR 9238 | 24-Hydroxycholesterol | BMS-852927 | Nagilactone B | RGX-104 | Rovazolac