Discovery of a new class of liver receptor homolog-1 (LRH-1) antagonists: virtual screening, synthesis and biological evaluation

Abstract

Targeting LRH-1: Virtual screening and molecular modeling were used to identify novel antagonists of liver receptor homolog-1 (LRH-1), an emerging therapeutic target for breast cancer. Hit compounds were synthesized and biologically assayed, and the preliminary results suggest that raloxifene-based analogues, substituted at the position C-7 of the benzothiophene ring, might generate an inactive protein conformation through binding and thus antagonize this nuclear receptor.

Keywords: antagonists; breast cancer; high-throughput virtual screening; ligand binding domains; nuclear receptor.