Biased Ligands of G Protein-Coupled Receptors (GPCRs): Structure–Functional Selectivity Relationships (SFSRs) and Therapeutic PotentialClick to copy article linkArticle link copied!
- Liang TanLiang TaniHuman Institute, ShanghaiTech University, 393 Middle Huaxia Road, Pudong District, Shanghai 201210, ChinaMore by Liang Tan
- Wenzhong YanWenzhong YaniHuman Institute, ShanghaiTech University, 393 Middle Huaxia Road, Pudong District, Shanghai 201210, ChinaMore by Wenzhong Yan
- John D. McCorvy*John D. McCorvy*J.D.M.: phone, +1 414-955-7635; e-mail, [email protected]Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, 8701 W. Watertown Plank Road, Milwaukee, Wisconsin 53226, United StatesMore by John D. McCorvy
- Jianjun Cheng*Jianjun Cheng*J.C.: phone, +86 21 20685237; e-mail, [email protected]iHuman Institute, ShanghaiTech University, 393 Middle Huaxia Road, Pudong District, Shanghai 201210, ChinaMore by Jianjun Cheng
Abstract

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.
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