Community guidelines for GPCR ligand bias: IUPHAR review 32

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    Final published version, 6.61 MB, PDF document

  • Peter Kolb
  • Terry Kenakin
  • Stephen P.H. Alexander
  • Marcel Bermudez
  • Laura M. Bohn
  • Christian S. Breinholt
  • Michel Bouvier
  • Stephen J. Hill
  • Evi Kostenis
  • Kirill A. Martemyanov
  • Rick R. Neubig
  • H. Ongun Onaran
  • Sudarshan Rajagopal
  • Bryan L. Roth
  • Jana Selent
  • Arun K. Shukla
  • Martha E. Sommer
  • Gloriam, David E.

GPCRs modulate a plethora of physiological processes and mediate the effects of one-third of FDA-approved drugs. Depending on which ligand activates a receptor, it can engage different intracellular transducers. This ‘biased signalling’ paradigm requires that we now characterize physiological signalling not just by receptors but by ligand–receptor pairs. Ligands eliciting biased signalling may constitute better drugs with higher efficacy and fewer adverse effects. However, ligand bias is very complex, making reproducibility and description challenging. Here, we provide guidelines and terminology for any scientists to design and report ligand bias experiments. The guidelines will aid consistency and clarity, as the basic receptor research and drug discovery communities continue to advance our understanding and exploitation of ligand bias. Scientific insight, biosensors, and analytical methods are still evolving and should benefit from and contribute to the implementation of the guidelines, together improving translation from in vitro to disease-relevant in vivo models.

Original languageEnglish
JournalBritish Journal of Pharmacology
Volume179
Issue number14
Pages (from-to)3651-3674
ISSN0007-1188
DOIs
Publication statusPublished - 2022

Bibliographical note

Themed Issue: Structure Guided Pharmacology of Membrane Proteins (BJP 75th Anniversary)

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