Ma_2020_Drug.Discov.Today_25_1682

Mounting evidence indicates that single-target drugs might be inadequate to achieve satisfactory therapeutic effects on complex diseases. Recently, increasing attention has been paid to developing drugs that can manipulate multiple targets to generate beneficial effects through potential synergy. G-protein-coupled receptors (GPCRs) become desirable targets for developing multitarget-directed ligands (MTDLs) because of their crucial roles in the pathophysiology of various human diseases and the accessibility of druggable sites at the cell surface. Herein, we review the most recent advances in the development of GPCR-targeted MTDLs in treating complex diseases, and discuss their potential therapeutic strategies to reveal current trends and shed insights into the utility of GPCR-targeted MTDLs for future drug design and development.