Biased ligands at G-protein-coupled receptors: promise and progress
| Autor: | Michael W. Lark, David G. Soergel, Aimee L. Crombie, Jonathan D. Violin |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
medicine.drug_class
Receptors Opioid mu Thiophenes Computational biology Pharmacology Biology Ligands Toxicology Receptor Angiotensin Type 1 Receptors G-Protein-Coupled Opioid receptor medicine Functional selectivity Animals Humans Spiro Compounds Receptor G protein-coupled receptor Drug discovery Ligand Angiotensin II Drug development Drug Design Angiotensin II Type 1 Receptor Blockers Oligopeptides |
| Zdroj: | Trends in Pharmacological Sciences. 35:308-316 |
| ISSN: | 0165-6147 |
| DOI: | 10.1016/j.tips.2014.04.007 |
| Popis: | Drug discovery targeting G protein-coupled receptors (GPCRs) is no longer limited to seeking agonists or antagonists to stimulate or block cellular responses associated with a particular receptor. GPCRs are now known to support a diversity of pharmacological profiles, a concept broadly referred to as functional selectivity. In particular, the concept of ligand bias, whereby a ligand stabilizes subsets of receptor conformations to engender novel pharmacological profiles, has recently gained increasing prominence. This review discusses how biased ligands may deliver safer, better tolerated, and more efficacious drugs, and highlights several biased ligands that are in clinical development. Biased ligands targeting the angiotensin II type 1 receptor and the μ opioid receptor illustrate the translation of the biased ligand concept from basic biology to clinical drug development. |
| Databáze: | OpenAIRE |
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