LXRβ Agonist

LXRβ ligand 1 is a LXR β ligand-binding domain agonist, with an EC₅₀ of 57 μM and a K_i of 28 μM against human LXR β. LXRβ ligand 1 forms hydrogen bonds with His435, stabilizes the His-Trp activation switch, and locks the ligand-binding domain in an agonist conformation; its tert-butyl moiety occupies a hydrophobic subpocket, while its phenyl moiety forms a π-π stacking interaction with Phe329. LXRβ ligand 1 serves as a structural unit for the development of LXRβ modulators.

AU403 is a potent, brain-penetrant, isoform-selective LXRβ/PPARδ dual agonist (EC₅₀ ≈ 45 nM for LXRβ and EC₅₀ ≈ 40 nM for PPARδ). AU403 is designed to bypass LXRα-driven hepatotoxicity. AU403 significantly improves cognitive functions and reduces amyloid-β plaque burden in 3xTg-AD mice. AU403 is a promising dual-acting agonist for the research of Alzheimer’s disease.

LXRβ agonist-2 is an orally active and selective LXRβ agonist. LXRβ agonist-2 increases high-density lipoprotein cholesterol levels without elevating plasma triglyceride levels. LXRβ agonist-2 decreases lipid accumulation area in the aortic arch. LXRβ agonist-2 can be used for the research of atherosclerosis.

LXRα agonist 1 is a selective LXRα agonist, with EC₅₀ values of 42 nM and 266 nM against purified LXRα and LXRβ, respectively. LXRα agonist 1 acts as a lipotoxicity inducer, triggering the production of toxic saturated fatty acids in tumor cells, and induces lipotoxicity-mediated cancer cell death when combined with the Raf inhibitor Sorafenib (HY-10201). LXRα agonist 1 can be used in the research of hepatocellular carcinoma.