Publication – GPCR Allosteric Sites


What is the potential of G-Protein Coupled Receptor allosteric sites in drug design?

In an editorial published in Future Medicinal Chemistry, Stephen Garland discusses the progress being made with the identification and exploitation of allosteric binding sites at G-Protein Coupled Receptors, their potential to open up targets that have otherwise proven intractable and to identify compounds with new and improved efficacy.

At least 5 allosteric sites appear to be available at GPCRs:
     1. Within the TM bundle at a site distinct from that used by the endogenous ligand;
     2. Within the extracellular loops in an “ectopic” site;
     3. On (rather than within) the extracellular loops;
     4. At an intracellular site;
     5. In one of possibly several membrane-facing sites.
The various sites have differences in terms of their properties and hence potential as targets for drug design.
The publication is available from or via doi:10.4155/fmc.14.32.