Thematic Minireview Series: New Directions in G Protein-Coupled Receptor Pharmacology [Signal Transduction]

June 30th, 2015 by Dohlman, H. G.

Over the past half century, The Journal of Biological Chemistry has been the venue for many landmark publications on the topic of G protein coupled receptors (GPCRs, also known as 7 transmembrane receptors). The GPCR superfamily in humans is comprised of about 800 members, and is the target of about one third of all pharmaceuticals. Most of these drugs target a very small subset of GPCRs, and do so by mimicking or competing with endogenous hormones and neurotransmitters. This thematic mini-review series examines some emerging trends in GPCR drug discovery. The first article describes efforts to systematically interrogate the human "GPCR-ome", including more than 150 uncharacterized "orphan" receptors. The second article describes recent efforts to target alternative receptor binding sites with drugs that act as allosteric modulators of orthosteric ligands. The third article describes how the recent expansion of GPCR structures is providing new opportunities for computer-guided drug discovery. Collectively these three articles provide a roadmap for the most important emerging trends in GPCR pharmacology.