Discovery and pharmacological effects of a novel GPR142 antagonist

  • J Recept Signal Transduct Res. 2017 Jun;37(3):290-296. doi: 10.1080/10799893.2016.1247861.
Michiko Murakoshi  1 ,  Harumi Kuwabara  2 ,  Miyuki Nagasaki  3 ,  Yu Mei Xiong  4 ,  Jeff D Reagan  4 ,  Hiroaki Maeda  5 ,  Futoshi Nara  3
Affiliations
  • 1. a Biological Research Department , Daiichi Sankyo RD Novare Co. Ltd. , Tokyo , Japan.
  • 2. b Pain & Neuroscience Laboratories, Research Function, R&D Division , Daiichi Sankyo Co. Ltd. , Tokyo , Japan.
  • 3. c Biologics & Immuno-Oncology Laboratories Research Function , R&D Division , Daiichi Sankyo Co. Ltd. , Tokyo , Japan.
  • 4. d Department of Cardio-Metabolic Disorders , Amgen, Inc. , South San Francisco , CA , USA.
  • 5. e Immunology & Inflammatory Disease Field , Asubio Pharma Co. Ltd. , Kobe , Japan.
PMID: 27807998 DOI: 10.1080/10799893.2016.1247861
Abstract

GPR142 is a G-protein-coupled receptor (GPCR), whose most potent and efficacious ligand has been reported as being the natural amino acid l-tryptophan. GPR142 is highly expressed in pancreatic β-cells and immune cells, suggesting the receptor may play a role in the pathogenesis and development of diabetes or inflammatory diseases. In a previous report, we developed GPR142 agonists as Insulin secretagogues. In this report, we show the discovery of a selective, potent small-molecule GPR142 antagonist, CLP-3094, and its pharmacological characteristics. These data support targeting this receptor for the treatment of chronic inflammatory diseases.

Keywords
GPR142 antagonist; KO mouse; anti-CII Ab-induced arthritis; inflammatory diseases; l-tryptophan.
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