Discovery of a potent G-protein-coupled receptor 119 agonist for the treatment of type 2 diabetes

Bioorg Med Chem. 2021 Apr 1:35:116071. doi: 10.1016/j.bmc.2021.116071. Epub 2021 Feb 13.

Abstract

The ever-growing prevalence of Type-2 diabetes in the world has an urgent need for multiple orally effective agents that can regulate glucose homeostasis. G-Protein coupled receptor 119 (GPR 119) agonists have demonstrated the glucose-dependent insulin secretion and showed beneficial effects on glycemic control in humans and/or relevant animal models. Herein, we describe our efforts towards identification of a potent and oral GPR 119 agonist 13c (ZY-G19), which showed in vitro potency in the cell-based assay and in vivo efficacy without exerting any significant signs of toxicity in relevant animal models.

Keywords: GPR119 agonist; Insulin sensitizers; Thiazolidinediones (TZDs); Type 2 diabetes mellitus (T2DM).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Female
  • Glucose Tolerance Test
  • Humans
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Structure
  • Rats
  • Rats, Wistar
  • Receptors, G-Protein-Coupled / agonists*
  • Receptors, G-Protein-Coupled / metabolism
  • Structure-Activity Relationship

Substances

  • GPR119 protein, human
  • Hypoglycemic Agents
  • Receptors, G-Protein-Coupled