title: Phenylalanine derivatives as GPR142 agonists for the treatment of type II diabetes.
abstract: GPR142 is a novel GPCR that is predominantly expressed in pancreatic β-cells. GPR142 agonists potentiate glucose-dependent insulin secretion, and therefore can reduce the risk of hypoglycemia. Optimization of our lead pyridinone-phenylalanine series led to a proof-of-concept compound 22, which showed in vivo efficacy in mice with dose-dependent increase in insulin secretion and a decrease in glucose levels.
authors.affiliation: Amgen Inc, 1120 Veterans Blvd., South San Francisco, CA 94080, USA. xdu@amgen.com
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Du
authors.forename: Yong-Jae
authors.initials: YJ
authors.lastname: Kim
authors.forename: Sujen
authors.initials: S
authors.lastname: Lai
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Mike
authors.initials: M
authors.lastname: Lizarzaburu
authors.forename: Simon
authors.initials: S
authors.lastname: Turcotte
authors.forename: Zice
authors.initials: Z
authors.lastname: Fu
authors.forename: Qingxiang
authors.initials: Q
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Alykhan
authors.initials: A
authors.lastname: Motani
authors.forename: Kozo
authors.initials: K
authors.lastname: Oda
authors.forename: Ryo
authors.initials: R
authors.lastname: Okuyama
authors.forename: Futoshi
authors.initials: F
authors.lastname: Nara
authors.forename: Michiko
authors.initials: M
authors.lastname: Murakoshi
authors.forename: Angela
authors.initials: A
authors.lastname: Fu
authors.forename: Jeff D
authors.initials: JD
authors.lastname: Reagan
authors.forename: Peter
authors.initials: P
authors.lastname: Fan
authors.forename: Yumei
authors.initials: Y
authors.lastname: Xiong
authors.forename: Wang
authors.initials: W
authors.lastname: Shen
authors.forename: Leping
authors.initials: L
authors.lastname: Li
authors.forename: Jonathan
authors.initials: J
authors.lastname: Houze
authors.forename: Julio C
authors.initials: JC
authors.lastname: Medina
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D005951:Glucose Tolerance Test; D057809:HEK293 Cells; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008861:Microsomes / Q000737:chemistry; D010649:Phenylalanine / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D001786:Blood Glucose; C501537:GPR142 protein, human; C511538:GPR142 protein, mouse; D007004:Hypoglycemic Agents; D007328:Insulin; D043562:Receptors, G-Protein-Coupled; D010649:Phenylalanine