title: Thematic Minireview Series: New Directions in G Protein-coupled Receptor Pharmacology.
abstract: 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 seven-transmembrane receptors). The GPCR superfamily in humans is composed 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 minireview 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.
authors.affiliation: From the Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599-7260 hdohlman@med.unc.edu.
authors.forename: Henrik G
authors.initials: HG
authors.lastname: Dohlman
mesh_terms: D000494:Allosteric Regulation; D017076:Computer-Aided Design; D055808:Drug Discovery; D006801:Humans; D008024:Ligands; D018716:Molecular Mimicry; D011485:Protein Binding; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D054852:Small Molecule Libraries
keywords: G protein-coupled receptor (GPCR); X-ray crystallography; allosteric regulation; drug discovery; functional genomics; molecular pharmacology