Development of novel ligands for peptide GPCRs

Curr Opin Pharmacol. 2016 Dec:31:57-62. doi: 10.1016/j.coph.2016.08.009. Epub 2016 Sep 5.

Abstract

Incretin based glucagon-like peptide-1 receptor (GLP-1R) agonists which target a G-protein coupled receptor (GPCR) are currently used in the treatment of type 2 diabetes. This review focuses on GPCRs from pancreatic β-cells, including GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucagon, somatostatin, pancreatic polypeptide (PP), cholecystokinin (CCK), peptide YY (PYY), oxyntomodulin (OXM) and ghrelin receptors. In addition, fatty acids GPCRs are thought to have an increasing role in regulating peptide secretions namely short fatty acids GPCR (GPR41, GPR43), medium chain fatty acid GPCR (GPR84), long chain fatty acid GPCR (GPR40, GPR120) and cannabinoid-like GPCR (GPR55, GPR119). Several pre-clinical and clinical trials are currently ongoing in peptide GPCR based therapies, including dual and triple agonist peptides which activate two or more GPCRs simultaneously.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Design
  • Fatty Acids
  • Glucagon-Like Peptide-1 Receptor / agonists
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Incretins / metabolism
  • Insulin-Secreting Cells / metabolism
  • Ligands
  • Peptides / metabolism
  • Receptors, G-Protein-Coupled / agonists*
  • Receptors, G-Protein-Coupled / metabolism

Substances

  • Fatty Acids
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Incretins
  • Ligands
  • Peptides
  • Receptors, G-Protein-Coupled