Emerging Approaches to GPCR Ligand Screening for Drug Discovery

Trends Mol Med. 2015 Nov;21(11):687-701. doi: 10.1016/j.molmed.2015.09.002. Epub 2015 Oct 16.

Abstract

The superfamily of G-protein-coupled receptors (GPCRs) represents the largest class of cell surface receptors and, thus, a prominent family of drug targets. Recently, there has been significant progress in determination of GPCR crystal structures. The structure-based ligand discovery of GPCRs is emerging as a powerful path to drug development. Sensor surface-immobilized GPCRs can identify direct receptor-ligand interactions of a range of chemical libraries. This type of screening shows great promise as an alternative strategy for ligand discovery. Here, we summarize the most recent developments of structure- and sensor-based GPCR ligand discovery. We also highlight certain areas where GPCRs harbor great potential for the development of novel therapeutics, emphasizing the strategic approaches that may yield significant breakthroughs.

Publication types

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

MeSH terms

  • Animals
  • Drug Discovery / methods*
  • Humans
  • Ligands
  • Models, Molecular
  • Receptors, G-Protein-Coupled / chemistry
  • Receptors, G-Protein-Coupled / metabolism*
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology

Substances

  • Ligands
  • Receptors, G-Protein-Coupled
  • Small Molecule Libraries