Discovery and pharmacological effects of a novel GPR142 antagonist

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
• l-tryptophan
• KO mouse
• anti-CII Ab-induced arthritis
• inflammatory diseases

Acknowledgements

We gratefully acknowledge Dr. Akiyoshi Fukamizu for the thoughtful advice. I am very grateful to Yayoi Mizutani for her valuable cooperation in my experiments.

Disclosure statement

The authors report that there are no conflicts of interest to declare.