Physiological relevance of GPCR oligomerization and its impact on drug discovery

Drug Discov Today. 2008 Dec;13(23-24):1059-66. doi: 10.1016/j.drudis.2008.09.002. Epub 2008 Oct 14.

Abstract

The potentially large functional and physiological diversity of G-protein coupled receptor (GPCR) dimers has generated a great deal of excitement about the opportunity that dimerization provides for enabling novel drug discovery. The discovery of physiologically relevant GPCR dimers suggests that new drug targets for diseases such as schizophrenia and pre-eclampsia can be developed by targeting dimers. Most of the previous work on GPCR dimers made use of the overexpression of differentially tagged GPCRs in heterologous cell systems. Current emphasis on the development of physiologically relevant cell systems that endogenously express the appropriate combination of GPCR dimers and accessory proteins is leading to dramatic increases in our understanding of GPCR dimers. These and other new tools such as GPCR-specific antibodies will be required to develop GPCR dimer specific drugs. Given that ligands are available for only a small percentage of the large number of potentially druggable GPCRs, the use of GPCR dimers might provide the necessary targets to increase the breadth and depth of receptors available for therapeutic interventions.

Publication types

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

MeSH terms

  • Animals
  • Dimerization
  • Drug Delivery Systems*
  • Drug Discovery / methods*
  • Gene Expression Regulation
  • Humans
  • Ligands
  • Receptors, G-Protein-Coupled / drug effects
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*

Substances

  • Ligands
  • Receptors, G-Protein-Coupled