title: Tools for GPCR drug discovery.
abstract: G-protein-coupled receptors (GPCRs) mediate many important physiological functions and are considered as one of the most successful therapeutic targets for a broad spectrum of diseases. The design and implementation of high-throughput GPCR assays that allow the cost-effective screening of large compound libraries to identify novel drug candidates are critical in early drug discovery. Early functional GPCR assays depend primarily on the measurement of G-protein-mediated 2nd messenger generation. Taking advantage of the continuously deepening understanding of GPCR signal transduction, many G-protein-independent pathways are utilized to detect the activity of GPCRs, and may provide additional information on functional selectivity of candidate compounds. With the combination of automated imaging systems and label-free detection systems, such assays are now suitable for high-throughput screening (HTS). In this review, we summarize the most widely used GPCR assays and recent advances in HTS technologies for GPCR drug discovery.
authors.affiliation: Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, China.
authors.forename: Ru
authors.initials: R
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Xie
mesh_terms: D055808:Drug Discovery / Q000379:methods; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D043562:Receptors, G-Protein-Coupled; D019204:GTP-Binding Proteins