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The Measurement of Receptor Signaling Bias

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G Protein-Coupled Receptors in Drug Discovery

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1335))

Abstract

This chapter describes a method to quantify biased signaling effects of agonists; this approach can furnish a scale for medicinal chemists to optimize biased profiles. Biased ligands have different pharmacological properties on a molecular level (stabilization of different receptor active states) and thus can have different pharmacological profiles therapeutically. The calculation of transduction ratios (ΔΔlog(τ/K A)) values (where τ is efficacy and K A a measure of affinity) allows the identification of agonists that demonstrate unique signaling either for different signaling pathways linked to the receptor, differences in cellular host, effects of receptor mutation, or receptor selectivity profiles. The procedure includes statistical methods to assess the significance of these effects.

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Author information

Authors and Affiliations

  1. Department of Pharmacology, University of North Carolina School of Medicine, Room 4042 Genetic Medicine Building, CB# 7365, 120 Mason Farm Road, Chapel Hill, NC, 27599-7365, USA

    Terry Kenakin

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  1. Terry Kenakin
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Correspondence to Terry Kenakin .

Editor information

Editors and Affiliations

  1. Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA

    Marta Filizola

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Kenakin, T. (2015). The Measurement of Receptor Signaling Bias. 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_11

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  • DOI: https://doi.org/10.1007/978-1-4939-2914-6_11

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2913-9

  • Online ISBN: 978-1-4939-2914-6

  • eBook Packages: Springer Protocols

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