Finding the Perfect Fit: Conformational Biosensors to Determine the Efficacy of GPCR Ligands.

ABSTRACT: G protein-coupled receptors (GPCRs) are highly druggable targets that adopt numerous conformations. A ligand's ability to stabilize specific conformation(s) of its cognate receptor determines its efficacy or ability to produce a biological response. Identifying ligands that produce different receptor conformations and potentially discrete pharmacological effects (e.g., biased agonists, partial agonists, antagonists, allosteric modulators) is a major goal in drug discovery and necessary to develop drugs with better effectiveness and fewer side effects. Fortunately, direct measurements of ligand efficacy, via receptor conformational changes are possible with the recent development of conformational biosensors. In this review, we discuss classical efficacy models, including the two-state mode

SUBMITTER: Olson KM 

PROVIDER: S-EPMC9469492 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature