Discovery and structure–activity relationship studies of indole derivatives as liver X receptor (LXR) agonists

Abstract A structurally novel liver X receptor (LXR) agonist ( 1 ) was identified from internal compound collection utilizing the combination of structure-based virtual screening and high-throughput gene profiling. Compound 1 increased ABCA1 gene expression by eightfold and SREBP1c by threefold in differentiated THP-1 macrophage cell lines. Confirmation of its agonistic activity against LXR was obtained in the co-factor recruitment and reporter transactivation assays. Structure–activity relationship studies on compound 1 are described.