Delineating biased ligand efficacy at 7TM receptors from an experimental perspective
| Autor: | Céline Galés, Jean-Michel Senard, Ségolène Galandrin, Mathias C. Poirot, Lauriane Onfroy |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Agonist medicine.drug_class Biology Ligands Biochemistry Receptors G-Protein-Coupled 03 medical and health sciences 0302 clinical medicine Cell surface receptor medicine Functional selectivity Animals Humans Receptor G protein-coupled receptor Translation (biology) Cell Biology 030104 developmental biology Immunology Biological Assay Cellular model Signal transduction Neuroscience 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | The International Journal of Biochemistry & Cell Biology. 77:251-263 |
| ISSN: | 1357-2725 |
| Popis: | During the last 10 years, the concept of "biased agonism" also called "functional selectivity" swamped the pharmacology of 7 transmembrane receptors and paved the way for developing signaling pathway-selective drugs with increased efficacy and less adverse effects. Initially thought to select the activation of only a subset of the signaling pathways by the reference agonist, bias ligands revealed higher complexity as they have been shown to stabilize variable receptor conformations that associate with distinct signaling events from the reference. Today, one major challenge relies on the in vitro determination of the bias and classification of these ligands, as a prerequisite for future in vivo and clinical translation. In this review, current experimental considerations for the bias evaluation related to choice of the cellular model, of the signaling pathway as well as of the assays are presented and discussed. |
| Databáze: | OpenAIRE |
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