title: Discovery of the imidazole-derived GPR40 agonist AM-3189.
abstract: As a follow-up to the GPR40 agonist AMG 837, which was evaluated in clinical trials for the treatment of type II diabetes, further optimization led to the discovery of AM-3189 (13k). AM-3189 is representative of a new class of compounds with minimal CNS penetration, superior pharmacokinetic properties and in vivo efficacy comparable to AMG 837.
authors.affiliation: Department of Therapeutic Discovery, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Metabolic Disorders, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors.forename: Daniel C-H
authors.initials: DC
authors.lastname: Lin
authors.affiliation: Department of Therapeutic Discovery, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Sharma
authors.affiliation: Department of Therapeutic Discovery, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors.forename: Jinqian
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Therapeutic Discovery, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors.forename: Liusheng
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Therapeutic Discovery, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors.forename: An-Rong
authors.initials: AR
authors.lastname: Li
authors.affiliation: Department of Therapeutic Discovery, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors.forename: Todd
authors.initials: T
authors.lastname: Kohn
authors.affiliation: Department of Therapeutic Discovery, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors.forename: Yingcai
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Therapeutic Discovery, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors.forename: Jiwen Jim
authors.initials: JJ
authors.lastname: Liu
authors.affiliation: Department of Therapeutic Discovery, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Bartberger
authors.affiliation: Department of Therapeutic Discovery, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors.forename: Julio C
authors.initials: JC
authors.lastname: Medina
authors.affiliation: Department of Metabolic Disorders, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors.forename: Run
authors.initials: R
authors.lastname: Zhuang
authors.affiliation: Department of Metabolic Disorders, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Metabolic Disorders, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Metabolic Disorders, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Pharmacokinetics & Drug Metabolism, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: Wong
authors.affiliation: Department of Pharmacokinetics & Drug Metabolism, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors.forename: George R
authors.initials: GR
authors.lastname: Tonn
authors.affiliation: Department of Therapeutic Discovery, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Houze
mesh_terms: D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008252:Macaca fascicularis; D051379:Mice; D015394:Molecular Structure; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000819:agonists*; D013329:Structure-Activity Relationship
chemical_list: C000609209:AM-3189; C473034:FFAR1 protein, human; D007093:Imidazoles; D043562:Receptors, G-Protein-Coupled; C029899:imidazole
keywords: AM-3189; AMG 837; Agonist; FFAR1; GPCR; GPR40; Insulin secretagogue; Type II diabetes