Discovery and structure-activity relationship studies of indole derivatives as liver X receptor (LXR) agonists.
Bakir F,
Kher S,
Pannala M,
Wilson N,
Nguyen T,
Sircar I,
Takedomi K,
Fukushima C,
Zapf J,
Xu K,
Zhang SH,
Liu J,
Morera L,
Schneider L,
Sakurai N,
Jack R,
Cheng JF.
Department of Chemistry, Tanabe Research Laboratories USA, Inc., 4540 Towne Centre Court, San Diego, CA 92121, USA.
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.
PMID: 17416521 [PubMed - indexed for MEDLINE]