How Ligands Illuminate GPCR Molecular Pharmacology

Cell. 2017 Jul 27;170(3):414-427. doi: 10.1016/j.cell.2017.07.009.

Abstract

G protein-coupled receptors (GPCRs), which are modulated by a variety of endogenous and synthetic ligands, represent the largest family of druggable targets in the human genome. Recent structural and molecular studies have both transformed and expanded classical concepts of receptor pharmacology and have begun to illuminate the distinct mechanisms by which structurally, chemically, and functionally diverse ligands modulate GPCR function. These molecular insights into ligand engagement and action have enabled new computational methods and accelerated the discovery of novel ligands and tool compounds, especially for understudied and orphan GPCRs. These advances promise to streamline the development of GPCR-targeted medications.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Discovery
  • Humans
  • Ligands
  • Models, Molecular
  • Molecular Targeted Therapy*
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / chemistry
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction

Substances

  • Ligands
  • Receptors, G-Protein-Coupled