title: Label-free whole-cell assays: expanding the scope of GPCR screening.
abstract: A new class of instruments offers an unprecedented combination of label-free detection with exquisite sensitivity to live-cell responses. These instruments can quantify G-protein-coupled receptor (GPCR) signaling through G(s), G(i) and G(q) pathways and in some cases distinguish G-protein coupling, with sensitivity high enough to detect endogenous receptors. Here, we review emerging data evaluating impedance- and optical-based label-free instruments for GPCR drug discovery. In comparison with traditional GPCR assays, we highlight strengths, weaknesses and future opportunities for label-free biosensors. The ability to qualitatively distinguish G-protein coupling has groundbreaking potential for assessing functional selectivity, a concept that is changing the way GPCR pharmacology is defined and screening strategies are designed.
authors.affiliation: Lead Generation Department, AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850, USA. clayscott3@gmail.com
authors.forename: Clay W
authors.initials: CW
authors.lastname: Scott
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Peters
mesh_terms: D000818:Animals; D001681:Biological Assay / Q000295:instrumentation*; D015374:Biosensing Techniques / Q000295:instrumentation*; D055808:Drug Discovery / Q000295:instrumentation* / Q000379:methods; D006801:Humans; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects*
chemical_list: D043562:Receptors, G-Protein-Coupled