Discovery of novel FFA4 (GPR120) receptor agonists with β-arrestin2-biased characteristics

Future Med Chem. 2015;7(18):2429-37. doi: 10.4155/fmc.15.160. Epub 2015 Dec 14.

Abstract

Background: Free fatty acid 4 (FFA4) (GPR120) receptor functions as a receptor for unsaturated long-chain free fatty acids by regulating the secretion of glucagon-like peptide-1 and suppressing the inflammatory process, in which these two distinct biological functions are modulated by two signaling pathways, Gq and β-arrestin2, respectively.

Results: By using pharmacophore modeling and virtual screening methods, several compounds are found with excellent activities for agonizing FFA4 receptor. It needs to be noted that among them, some molecules demonstrate appealing β-arrestin2-biased properties for the FFA4 receptor.

Conclusion: These compounds may serve as the useful toolkits for detecting differential biased mechanism and developing new candidate therapeutic agents of the FFA4 receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arrestins / metabolism*
  • Drug Discovery*
  • Drug Evaluation, Preclinical
  • Humans
  • Molecular Structure
  • Receptors, G-Protein-Coupled / agonists*
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction / drug effects
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • beta-Arrestins

Substances

  • Arrestins
  • FFAR4 protein, human
  • Receptors, G-Protein-Coupled
  • Small Molecule Libraries
  • beta-Arrestins