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High-Throughput Screening for Allosteric Modulators of GPCRs

  • Robert L. BertekapJr.
  • Neil T. Burford
  • Zhuyin Li
  • Andrew Alt
Part of the Methods in Molecular Biology book series (MIMB, volume 1335)

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.

Key words

G protein-coupled receptor Allosteric HTS NAM PAM SAM Calcium flux FLIPR FDSS 

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Robert L. BertekapJr.
    • 1
  • Neil T. Burford
    • 1
  • Zhuyin Li
    • 1
  • Andrew Alt
    • 1
  1. 1.Lead Discovery, Bristol-Myers Squibb CompanyWallingfordUSA

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