LXR-623 is a is a highly selective and orally bioavailable synthetic agonist of Liver X receptors (LXR) alpha and beta that has shown promise in animal models of atherosclerosis. In nonhuman primates with normal lipid levels, LXR-623 significantly reduced total (50-55%) and LDL-cholesterol (LDLc) (70-77%) in a time- and dose-dependent manner and increased expression of the target genes ABCA1 and ABCG1 in peripheral blood cells of rats, mice and monkeys. LXR-623 demonstrated efficacy for reducing lesion progression in the murine LDLR(-/-) atherosclerosis model with no associated increase in hepatic lipogenesis either in this model or Syrian hamsters and displayed a unique and favorable pharmacological profile suggesting it may be suitable for evaluation in patients with atherosclerotic dyslipidemia. Results from a single ascending-dose study of the safety, pharmacokinetics, and pharmacodynamics of LXR-623 in healthy humans confirmed the effect of LXR-623 concentration on ABCA1 and ABCG1 expression. LXR-623 was absorbed rapidly with peak concentrations (Cmax) achieved at about 2 hours and increased Cmax and area under the concentration-time curve in a dose-proportional manner. The mean terminal disposition half-life was between 41 and 43 hours independently of dose. Central nervous system—related adverse events were observed at the 2 top doses tested. LXR-623 showed brain penetration and caused tumor regression in a glioblastoma (GBM) mouse model which characterize it as a potentially potent, highly-specific anti-GBM therapy.