Bias translation: The final frontier?

Publisher: Wiley Country of Publication: England NLM ID: 7502536 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5381 (Electronic) Linking ISSN: 00071188 NLM ISO Abbreviation: Br J Pharmacol Subsets: MEDLINE

Publication: London : Wiley
Original Publication: London, Macmillian Journals Ltd.

Signal Transduction*; Ligands

Biased signalling is a natural result of GPCR allosteric function and should be expected from any and all synthetic and natural agonists. Therefore, it may be encountered in all agonist discovery projects and must be considered as a beneficial (or possible detrimental) feature of new candidate molecules. While bias is detected easily, the synoptic nature of GPCR signalling makes translation of simple in vitro bias to complex in vivo systems problematic. The practical outcome of this is a difficulty in predicting the therapeutic value of biased signalling due to the failure of translation of identified biased signalling to in vivo agonism. This is discussed in this review as well as some new ways forward to improve this translation process and better exploit this powerful pharmacologic mechanism.
(© 2024 British Pharmacological Society.)

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Keywords: biased signalling; drug discovery; receptor agonism

0 (Ligands)

Date Created: 20240301 Date Completed: 20240412 Latest Revision: 20240412

20240412

10.1111/bph.16335

38424747