Exploring the specific role of GPCRs dimerization in drug discovery

doi:10.5246/jcps.2011.06.068

Abstract

Abstract:

G-protein-coupled receptors (GPCRs) are G-protein-coupled heptaspanning-membrane receptors. This group has thousands of members and is one of the important drug targets, accounting for 40%-50% of the drugs currently on the market. In the last decade, there has been a substantial re-evaluation of the assumption that GPCRs exist primarily as monomeric polypeptides, with support increasing for a model in which GPCRs can exist as homo- or hetero- dimers or even high-order oligomers. GPCRs dimers are hot research topics. Recent reports suggest that homo- or hetero- dimers exhibit "specific" functional properties which are distinct from monomeric receptors, involving agonist recognition, signaling, trafficking, and so on. Meanwhile, the occurrence of dimers with different pharmacological and signaling properties opens a completely new field in the search for novel drug targets useful to combat a variety of diseases and with potentially fewer side effects. In this paper, we will mainly review their specific structures and signal transduction, which help us reach for the high-hanging fruits in GPCRs drug discovery.

Key words: G-protein-coupled receptors, Receptor dimers, Signal transduction, Drug discovery

CLC Number:

R915

Supporting:

Xin Cai, Jing Chen, Bo Bai^*. Exploring the specific role of GPCRs dimerization in drug discovery[J]. , DOI: 10.5246/jcps.2011.06.068.

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