Vol. 4, Issue 2, Part F (2022)

G protein-coupled receptors (GPCRs) represent one of the largest and most diverse families of membrane proteins involved in signal transduction. They are crucial targets for a significant portion of therapeutic drugs. Allosteric modulators, which bind to sites distinct from the orthosteric ligand-binding site, offer several advantages, including improved selectivity and reduced side effects. This review provides a comprehensive overview of recent advances in the design of allosteric modulators for GPCRs, discussing key principles, methodologies, and therapeutic implications. The review also explores the structural basis of allosteric modulation, computational strategies for identifying allosteric sites, and the latest developments in the therapeutic targeting of GPCRs using allosteric modulators.