title: Identification and structure-activity relationship of phenolic acyl hydrazones as selective agonists for the estrogen-related orphan nuclear receptors ERRbeta and ERRgamma.
abstract: The first small molecule agonists of the estrogen-related receptors have been identified. GSK4716 (3) and GSK9089 (4) show binding to ERRgamma with remarkable selectivity over the classical estrogen receptors. Notably, in cell-based reporter assays, 3 mimics the protein ligand PGC-1alpha in activation of human ERRbeta and ERRgamma.
authors.affiliation: Discovery Research, GlaxoSmithKline, Five Moore Drive, Research Triangle Park, North Carolina 27707, USA. william.j.zuercher@gsk.com
authors.forename: William J
authors.initials: WJ
authors.lastname: Zuercher
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Gaillard
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Orband-Miller
authors.forename: Esther Y H
authors.initials: EY
authors.lastname: Chao
authors.forename: Barry G
authors.initials: BG
authors.lastname: Shearer
authors.forename: David G
authors.initials: DG
authors.lastname: Jones
authors.forename: Aaron B
authors.initials: AB
authors.lastname: Miller
authors.forename: Jon L
authors.initials: JL
authors.lastname: Collins
authors.forename: Donald P
authors.initials: DP
authors.lastname: McDonnell
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Willson
mesh_terms: D001667:Binding, Competitive; D047629:Estrogen Receptor beta / Q000819:agonists* / Q000235:genetics; D031541:Fluorescence Resonance Energy Transfer; D017930:Genes, Reporter; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008024:Ligands; D018716:Molecular Mimicry; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010636:Phenols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000819:agonists* / Q000235:genetics; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000096:biosynthesis
chemical_list: D047629:Estrogen Receptor beta; D006360:Heat-Shock Proteins; D006834:Hydrazines; D008024:Ligands; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010636:Phenols; D011960:Receptors, Estrogen; D014157:Transcription Factors; C425824:estrogen receptor gamma