title: Potent and Orally Bioavailable GPR142 Agonists as Novel Insulin Secretagogues for the Treatment of Type 2 Diabetes.
abstract: GPR142 is a G protein-coupled receptor that is predominantly expressed in pancreatic β-cells. GPR142 agonists stimulate insulin secretion in the presence of high glucose concentration, so that they could be novel insulin secretagogues with reduced or no risk of hypoglycemia. We report here the optimization of HTS hit compound 1 toward a proof of concept compound 33, which showed potent glucose lowering effects during an oral glucose tolerance test in mice and monkeys.
authors.affiliation: Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
authors.forename: Narihiro
authors.initials: N
authors.lastname: Toda
authors.affiliation: Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Hao
authors.affiliation: Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ogawa
authors.affiliation: Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
authors.forename: Kozo
authors.initials: K
authors.lastname: Oda
authors.affiliation: Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Ming
authors.initials: M
authors.lastname: Yu
authors.affiliation: Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Zice
authors.initials: Z
authors.lastname: Fu
authors.affiliation: Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Yongjae
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Mike
authors.initials: M
authors.lastname: Lizarzaburu
authors.affiliation: Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Sarah
authors.initials: S
authors.lastname: Lively
authors.affiliation: Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Shauna
authors.initials: S
authors.lastname: Lawlis
authors.affiliation: Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Murakoshi
authors.affiliation: Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
authors.forename: Futoshi
authors.initials: F
authors.lastname: Nara
authors.affiliation: Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Watanabe
authors.affiliation: Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Jeff D
authors.initials: JD
authors.lastname: Reagan
authors.affiliation: Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Hui
authors.initials: H
authors.lastname: Tian
authors.affiliation: Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Angela
authors.initials: A
authors.lastname: Fu
authors.affiliation: Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Alykhan
authors.initials: A
authors.lastname: Motani
authors.affiliation: Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Qingxiang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Yi-Jyun
authors.initials: YJ
authors.lastname: Lin
authors.affiliation: Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Run
authors.initials: R
authors.lastname: Zhuang
authors.affiliation: Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Peter
authors.initials: P
authors.lastname: Fan
authors.affiliation: Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Julio
authors.initials: J
authors.lastname: Medina
authors.affiliation: Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
authors.forename: Leping
authors.initials: L
authors.lastname: Li
authors.affiliation: Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Izumi
authors.affiliation: Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Okuyama
authors.affiliation: Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Shibuya
keywords: GPR142; agonist; diabetes; glucose lowering; insulin secretagogue