Covalent allosteric modulation: An emerging strategy for GPCRs drug discovery.

ABSTRACT: Designing covalent allosteric modulators brings new opportunities to the field of drug discovery towards G-protein-coupled receptors (GPCRs). Targeting an allosteric binding pocket can allow a modulator to have protein subtype selectivity and low drug resistance. Utilizing covalent warheads further enables the modulator to increase the binding potency and extend the duration of action. This review starts with GPCR allosteric modulation to discuss the structural biology of allosteric binding pockets, the different types of allosteric modulators, as well as the advantages of employing allosteric modulation. This is followed by a discussion on covalent modulators to clarify how covalent ligands can benefit the receptor modulation and to illustrate moieties that can commonly be used as covalen

SUBMITTER: Bian Y 

PROVIDER: S-EPMC9948676 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature