Abstract
The continued evolution of our understanding of G protein-coupled receptor (GPCR) signaling has revealed new opportunities for drug discovery. Specifically, biased agonism at GPCRs and allosteric modulation of GPCRs both represent emerging areas of GPCR biology that hold promise for the development of novel GPCR-targeted therapeutics that may provide greater therapeutic efficacy and/or improved side-effect profiles. To obtain initial chemical leads, high-throughput screening (HTS) of a large compound library for the desired activity is often deployed during the early stages of a discovery program. The identification of allosteric modulators, in particular, poses significant challenges for HTS. We describe several HTS protocols designed for the identification of GPCR ligands, with a particular focus on the identification of allosteric modulators.
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Bertekap, R.L., Burford, N.T., Li, Z., Alt, A. (2015). High-Throughput Screening for Allosteric Modulators of GPCRs. In: Filizola, M. (eds) G Protein-Coupled Receptors in Drug Discovery. Methods in Molecular Biology, vol 1335. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2914-6_15
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DOI: https://doi.org/10.1007/978-1-4939-2914-6_15
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-2913-9
Online ISBN: 978-1-4939-2914-6
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