title: G Protein-coupled Receptor Biased Agonism.
abstract: G protein-coupled receptors are the largest family of targets for current therapeutics. The classic model of their activation was binary, where agonist binding induced an active conformation and subsequent downstream signaling. Subsequently, the revised concept of biased agonism emerged, where different ligands at the same G protein-coupled receptor selectively activate one downstream pathway versus another. Advances in understanding the mechanism of biased agonism have led to the development of novel ligands, which have the potential for improved therapeutic and safety profiles. In this review, we summarize the theory and most recent breakthroughs in understanding biased signaling, examine recent laboratory investigations concerning biased ligands across different organ systems, and discuss the promising clinical applications of biased agonism.
authors.affiliation: Departments of *Medicine; and †Pediatrics, Duke University Medical Center, Durham, NC.
authors.forename: Sima Y
authors.initials: SY
authors.lastname: Hodavance
authors.forename: Clarice
authors.initials: C
authors.lastname: Gareri
authors.forename: Rachel D
authors.initials: RD
authors.lastname: Torok
authors.forename: Howard A
authors.initials: HA
authors.lastname: Rockman
mesh_terms: D000818:Animals; D001665:Binding Sites; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D008024:Ligands; D058990:Molecular Targeted Therapy; D011485:Protein Binding; D011487:Protein Conformation; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D043562:Receptors, G-Protein-Coupled