GW3965 is a liver X receptor full agonist on hLXRα and hLXRβ. GW3965 has an EC50 = 125 nM in a cell-free ligand-sensing assay of LXRα and profiles as a full agonist on hLXRα and hLXRβ in cell-based assays with EC50 = 190 nM and 30 nM, respectively. Angiotensin II-mediated increases in blood pressure can be reduced by GW3965 hydrochloride. In HepG2 cells, the EC50 for GW3965 is greater than 4 μM. In an animal study, GW3965 hydrochloride decreased lesion area by 53% 34% in male and female LDLR-/- mice, respectively. GW3965 induced expression of ATP-binding cassettes A1 and G1 in modified low-density lipoprotein-loaded macrophages in vitro as well as in the aortas of hyperlipidemic mice. Additionally, GW3965 hydrochloride increases ABCA1 gene expression and raises circulating HDL levels. GW3965 hydrochloride displays potent antiatherogenic activity in mouse models of atherosclerosis.