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Journal Article
Review
Bias translation: The final frontier?
British Journal of Pharmacology 2024 Februrary 30
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.
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