title: 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.
authors.affiliation: Department of Chemistry, Imperial College London, London, SW7 2AZ (England).
authors.forename: Jullien
authors.initials: J
authors.lastname: Rey
authors.forename: Haipeng
authors.initials: H
authors.lastname: Hu
authors.forename: Fiona
authors.initials: F
authors.lastname: Kyle
authors.forename: Chun-Fui
authors.initials: CF
authors.lastname: Lai
authors.forename: Laki
authors.initials: L
authors.lastname: Buluwela
authors.forename: R Charles
authors.initials: RC
authors.lastname: Coombes
authors.forename: Eric A
authors.initials: EA
authors.lastname: Ortlund
authors.forename: Simak
authors.initials: S
authors.lastname: Ali
authors.forename: James P
authors.initials: JP
authors.lastname: Snyder
authors.forename: Anthony G M
authors.initials: AG
authors.lastname: Barrett
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D019556:COS Cells; D002522:Chlorocebus aethiops; D015195:Drug Design; D005260:Female; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D011487:Protein Conformation / Q000187:drug effects; D020849:Raloxifene Hydrochloride / Q000031:analogs & derivatives* / Q000494:pharmacology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D008024:Ligands; C082631:NR5A2 protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D020849:Raloxifene Hydrochloride