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

  • Bioorg Med Chem Lett. 2007 Jun 15;17(12):3473-9. doi: 10.1016/j.bmcl.2007.03.076.
Farid Bakir  1 ,  Sunil Kher ,  Madhavi Pannala ,  Norma Wilson ,  Trang Nguyen ,  Ila Sircar ,  Kei Takedomi ,  Chiaki Fukushima ,  James Zapf ,  Kui Xu ,  Shao-Hui Zhang ,  Juping Liu ,  Lisa Morera ,  Lisa Schneider ,  Naoki Sakurai ,  Rick Jack ,  Jie-Fei Cheng
Affiliations
  • 1. Department of Chemistry, Tanabe Research Laboratories USA, Inc., 4540 Towne Centre Court, San Diego, CA 92121, USA.
PMID: 17416521 DOI: 10.1016/j.bmcl.2007.03.076
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.