title: Tuning up the right signal: chemical and genetic approaches to study GPCR functions.
abstract: The G protein-coupled receptor (GPCR) family is among the most druggable families in the human proteome. GPCRs are involved in most physiological processes, and our ability to modulate their activity is a hallmark of modern pharmacology. The means by which the activity of GPCRs can be modulated have been expanded by emerging data and concepts in pharmacology, which has created new strategies for their control. These new approaches will lead to the generation of more potent, selective, and efficient pharmaceutics, while reducing inappropriate actions and adverse effects. Herein, we review and comment on some recent advances in chemical and genetic approaches to the profiling of GPCR function, as well as the validation of orphan GPCRs as potential therapeutic targets using engineered receptors.
authors.affiliation: Department of Pharmacology, Program in Neuroscience and Division of Chemical Biology and Medicinal Chemistry, and NIMH Psychoactive Drug Screening Program, University of North Carolina, Chapel Hill Medical School, 4072 Genetic Medicine Building, Chapel Hill, NC 27514, United States. Electronic address: giguere.pm@gmail.com.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Giguere
authors.affiliation: Department of Pharmacology, Program in Neuroscience and Division of Chemical Biology and Medicinal Chemistry, and NIMH Psychoactive Drug Screening Program, University of North Carolina, Chapel Hill Medical School, 4072 Genetic Medicine Building, Chapel Hill, NC 27514, United States.
authors.forename: Wesley K
authors.initials: WK
authors.lastname: Kroeze
authors.affiliation: Department of Pharmacology, Program in Neuroscience and Division of Chemical Biology and Medicinal Chemistry, and NIMH Psychoactive Drug Screening Program, University of North Carolina, Chapel Hill Medical School, 4072 Genetic Medicine Building, Chapel Hill, NC 27514, United States. Electronic address: bryan_roth@med.unc.edu.
authors.forename: Bryan L
authors.initials: BL
authors.lastname: Roth
mesh_terms: D000818:Animals; D055808:Drug Discovery; D006801:Humans; D008967:Molecular Biology; D010600:Pharmacology; D015202:Protein Engineering; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015203:Reproducibility of Results
chemical_list: D043562:Receptors, G-Protein-Coupled