Impact of GPCR Structures on Drug Discovery

Structures of 70 unique G protein-coupled receptors (GPCRs) have been determined, with over 370 structures in total bound to different ligands and the receptors in various conformational states. Structure-based drug design has been applied to an increasing number of GPCR targets over the past decade and now a few of these drug candidates have entered clinical trials. Given the length of time required for a drug to reach the market, there are no documented examples of licensed drugs being developed with the aid of a structure, but this is likely to change as current efforts come to fruition. The promise of the intensive structural investigations of GPCRs over the past decade was that they would improve and expedite the design of drugs targeting this important therapeutic class of proteins. Tate & colleagues examine whether this strategy has paid off.