title: Identification of a subtype selective human PPARalpha agonist through parallel-array synthesis.
abstract: Using solid-phase, parallel-array synthesis, a series of urea-substituted thioisobutyric acids was synthesized and assayed for activity on the human PPAR subtypes. GW7647 (3) was identified as a potent human PPARalpha agonist with approximately 200-fold selectivity over PPARgamma and PPARdelta, and potent lipid-lowering activity in animal models of dyslipidemia. GW7647 (3) will be a valuable chemical tool for studying the biology of PPARalpha in human cells and animal models of disease.
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC 27709-3398, USA. pjb5890@gsk.com
authors.forename: P J
authors.initials: PJ
authors.lastname: Brown
authors.forename: L W
authors.initials: LW
authors.lastname: Stuart
authors.forename: K P
authors.initials: KP
authors.lastname: Hurley
authors.forename: M C
authors.initials: MC
authors.lastname: Lewis
authors.forename: D A
authors.initials: DA
authors.lastname: Winegar
authors.forename: J G
authors.initials: JG
authors.lastname: Wilson
authors.forename: W O
authors.initials: WO
authors.lastname: Wilkison
authors.forename: O R
authors.initials: OR
authors.lastname: Ittoop
authors.forename: T M
authors.initials: TM
authors.lastname: Willson
mesh_terms: D000818:Animals; D002087:Butyrates / Q000494:pharmacology; D006224:Cricetinae; D004041:Dietary Fats / Q000494:pharmacology; D015195:Drug Design; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy; D000960:Hypolipidemic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D014157:Transcription Factors / Q000819:agonists*
chemical_list: D002087:Butyrates; D004041:Dietary Fats; D000960:Hypolipidemic Agents; D010671:Phenylurea Compounds; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C121804:GW 9578