alexa Cellular assays as portals to seven-transmembrane receptor-based drug discovery.

Journal of Bioengineering and Bioelectronics

Author(s): Kenakin TP

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Abstract As technology advances to the point at which various behaviours of seven-transmembrane (7TM) receptors (also known as G protein-coupled receptors (GPCRs)) can be observed individually, it is clear that, rather than being 'on-off' switches, 7TM receptors are more akin to 'microprocessors' of information. This has introduced the phenomenon of functional selectivity, whereby certain ligands initiate only portions of the signalling mechanisms mediated by a given receptor, which has opened new horizons for drug discovery. The need to discover new 7TM receptor-ligand behaviours and quantify the effect of the drug on these complex systems, to guide medicinal chemistry, puts the pharmacological assay into the spotlight. This Perspective outlines the return to whole-system assays from reductionist recombinant systems, and discusses how the efficacy of a drug is linked to the particular assay used to observe its effects. It also highlights how these new assays are adding value to the drug discovery process. This article was published in Nat Rev Drug Discov and referenced in Journal of Bioengineering and Bioelectronics

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