High content screening for G protein-coupled receptors using cell-based protein translocation assays.

摘要: G protein-coupled receptors (GPCRs) have been one of the most productive classes drug targets for several decades, and new technologies GPCR-based discovery promise to keep this field active years come. While molecular screens GPCR receptor agonist- antagonist-based drugs will continue be valuable tools, exciting developments in involve cell-based assays function. Some strategies, such as use β-arrestin a surrogate marker function, already reduced practice, used tools years. The application high content screening has opened up additional possibilities, direct tracking GPCRs, proteins other signaling pathway components using intracellular translocation assays. These provide capability probe function at cellular level with better resolution than previously possible, offer practical strategies more definitive selectivity evaluation counter-screening early stages discovery. potential is described, proof-of-concept data from pilot screen CXCR4 assay are presented. This chemokine highly relevant target which plays an important role pathogenesis inflammatory disease also shown co-receptor entry HIV into cells well play metastasis certain cancer cells.