Structures of G protein-coupled receptors reveal new opportunities for drug discovery

Robert M Cooke; Alastair J H Brown; Fiona H Marshall; Jonathan S Mason

doi:10.1016/j.drudis.2015.08.003

Structures of G protein-coupled receptors reveal new opportunities for drug discovery

Drug Discov Today. 2015 Nov;20(11):1355-64. doi: 10.1016/j.drudis.2015.08.003. Epub 2015 Aug 22.

Authors

Robert M Cooke¹, Alastair J H Brown¹, Fiona H Marshall¹, Jonathan S Mason²

Affiliations

¹ Heptares Therapeutics, Biopark, Broadwater Road, Welwyn Garden City, Hertfordshire AL7 3AX, UK.
² Heptares Therapeutics, Biopark, Broadwater Road, Welwyn Garden City, Hertfordshire AL7 3AX, UK. Electronic address: jon.mason@heptares.com.

PMID: 26303408
DOI: 10.1016/j.drudis.2015.08.003

Abstract

X-ray structures of G protein-coupled receptors (GPCRs) have now been reported for more than 60 ligands and 20 receptors, including examples from GPCR classes A, B, C and F. The new structures show previously unobtainable details of interactions between GPCRs and ligands, including the roles of lipophilic regions and water molecules as key drivers of binding. In addition, the structures have revealed several surprising ligand-binding modes, including sites outside the orthosteric pocket. This new information is dramatically changing the way we approach GPCR drug discovery.

Publication types

Review

MeSH terms

Binding Sites
Drug Design*
Drug Discovery / methods*
Humans
Ligands
Protein Binding
Receptors, G-Protein-Coupled / chemistry*
Receptors, G-Protein-Coupled / metabolism

Substances

Ligands
Receptors, G-Protein-Coupled