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International Union of Basic and Clinical Pharmacology. Guidelines for GPCR ligand bias
  • +15
  • Peter Kolb,
  • Terry Kenakin,
  • Stephen Alexander,
  • Marcel Bermudez,
  • Laura Bohn,
  • Christian Breinholt,
  • Michel Bouvier,
  • Frederick Ehlert,
  • Stephen Hill,
  • Kirill A. Martemyanov,
  • Richard D Neubig,
  • Ongun Onaran,
  • Sudar Rajagopal,
  • Bryan Roth,
  • Jana Selent,
  • Arun Shukla,
  • Martha Sommer,
  • David Gloriam
Peter Kolb
Philipps-Universitat Marburg
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Terry Kenakin
GlaxoSmithKline
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Stephen Alexander
Associate Professor in Molecular Pharmacology
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Marcel Bermudez
Freie Universitaet Berlin
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Laura Bohn
The Scripps Research Institute
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Christian Breinholt
University of Copenhagen
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Michel Bouvier
Université de Montréal
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Frederick Ehlert
University of California Irvine
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Stephen Hill
University of Nottingham
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Kirill A. Martemyanov
Scripps Res Inst Florida
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Richard D Neubig
Michigan State University
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Ongun Onaran
Ankara University Faculty of Medicine
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Sudar Rajagopal
Duke University
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Bryan Roth
University of North Carolina at Chapel Hill School of Medicine
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Jana Selent
Pompeu Fabra
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Arun Shukla
Indian Institute of Technology Kanpur
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Martha Sommer
Charité Universitätsmedizin Berlin
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David Gloriam
University of Copenhagen
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Abstract

G protein-coupled receptors modulate a plethora of physiological processes and mediate the effects of one-third of FDA-approved drugs. Notably, depending on which ligand has activated a particular receptor, it can engage different intracellular transducers. This paradigm of ligand-dependent ‘biased signaling’ dictates a need to advance beyond the level of receptors to consider the combined ligand-receptor pair in order to understand physiological signaling. Bias signaling also has the potential to improve medicines by reducing adverse effects. However, this is challenged by inconsistent interpretation of results and lack of commonly agreed guidelines. Here, we present recommended terminology and guidelines to conduct, report and quantify bias in a comparable and reproducible fashion. We expect these recommendations will facilitate a common understanding of experiments and findings across basic receptor research and drug discovery, while the area and the analytical methods to measure bias are still evolving, especially in complex cellular, tissue and organismal systems.

Peer review status:ACCEPTED

23 Aug 2021Submitted to British Journal of Pharmacology
23 Aug 2021Submission Checks Completed
23 Aug 2021Assigned to Editor
26 Aug 2021Reviewer(s) Assigned
19 Nov 2021Review(s) Completed, Editorial Evaluation Pending
22 Nov 2021Editorial Decision: Revise Minor
24 Dec 20211st Revision Received
03 Jan 2022Submission Checks Completed
03 Jan 2022Assigned to Editor
04 Jan 2022Review(s) Completed, Editorial Evaluation Pending
05 Jan 2022Editorial Decision: Revise Minor
11 Jan 20222nd Revision Received
11 Jan 2022Submission Checks Completed
11 Jan 2022Assigned to Editor
12 Jan 2022Review(s) Completed, Editorial Evaluation Pending
13 Jan 2022Editorial Decision: Accept