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Bias Translation: The Final Frontier?
  • Terry Kenakin
Terry Kenakin
The University of North Carolina at Chapel Hill School of Medicine

Corresponding Author:kenakin@email.unc.edu

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Abstract

Biased signaling is a natural result of GPCR allosteric function and should be expected from any and all synthetic 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 easily detected , the synoptic nature of GPCR signaling 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 signaling due to the failure of translation of identified biased signaling 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 activity.
03 Sep 2023Submitted to British Journal of Pharmacology
04 Sep 2023Submission Checks Completed
04 Sep 2023Assigned to Editor
04 Sep 2023Reviewer(s) Assigned
19 Sep 2023Review(s) Completed, Editorial Evaluation Pending
21 Sep 2023Editorial Decision: Revise Minor
24 Oct 20231st Revision Received
26 Oct 2023Submission Checks Completed
26 Oct 2023Assigned to Editor
30 Oct 2023Review(s) Completed, Editorial Evaluation Pending
31 Oct 2023Editorial Decision: Accept