Tools for GPCR drug discovery

G-protein-coupled receptors (GPCRs) mediate many important physiological functions andare considered as one of the most successful therapeutic targets for a broad spectrum ofdiseases. The design and implementation of high-throughput GPCR assays that allow thecost-effective screening of large compound libraries to identify novel drug candidates arecritical in early drug discovery. Early functional GPCR assays depend primarily on themeasurement of G-protein-mediated 2nd messenger generation. Taking advantage of thecontinuously deepening understanding of GPCR signal transduction, manyG-protein-independent pathways are utilized to detect the activity of GPCRs, and mayprovide additional information on functional selectivity of candidate compounds. With thecombination of automated imaging systems and label-free detection systems, such assays arenow suitable for high-throughput screening (HTS). In this review, we summarize the mostwidely used GPCR assays and recent advances in HTS technologies for GPCR drugdiscovery.