Biased Ligands of G Protein-Coupled Receptors (GPCRs): Structure-Functional Selectivity Relationships (SFSRs) and Therapeutic Potential. J Med Chem 2018 Nov 21;61(22):9841-9878
Date
06/26/2018Pubmed ID
29939744DOI
10.1021/acs.jmedchem.8b00435Scopus ID
2-s2.0-85049218486 (requires institutional sign-in at Scopus site) 117 CitationsAbstract
G protein-coupled receptors (GPCRs) signal through both G-protein-dependent and G-protein-independent pathways, and β-arrestin recruitment is the most recognized one of the latter. Biased ligands selective for either pathway are expected to regulate biological functions of GPCRs in a more precise way, therefore providing new drug molecules with superior efficacy and/or reduced side effects. During the past decade, biased ligands have been discovered and developed for many GPCRs, such as the μ opioid receptor, the angiotensin II receptor type 1, the dopamine D2 receptor, and many others. In this Perspective, recent advances in this field are reviewed by discussing the structure-functional selectivity relationships (SFSRs) of GPCR biased ligands and the therapeutic potential of these molecules. Further understanding of the biological functions associated with each signaling pathway and structural basis for biased signaling will facilitate future drug design in this field.
Author List
Tan L, Yan W, McCorvy JD, Cheng JAuthor
John McCorvy PhD Associate Professor in the Cell Biology Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsDrug Discovery
Humans
Ligands
Receptors, G-Protein-Coupled
Signal Transduction
Structure-Activity Relationship
