Journal
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 52
Volume 52, Issue -, Pages 179-197Publisher
ANNUAL REVIEWS
DOI: 10.1146/annurev.pharmtox.010909.105800
Keywords
GRKs; pharmacological bias; drug discovery; efficacy
Categories
Funding
- Howard Hughes Medical Institute Funding Source: Medline
- NHLBI NIH HHS [HL 70631, R01 HL016037, R01 HL16037, R01 HL070631] Funding Source: Medline
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL016037, R01HL070631] Funding Source: NIH RePORTER
Ask authors/readers for more resources
The concept of biased agonism has recently come to the fore with the realization that seven-transmembrane receptors (7TMRs, also known as G protein-coupled receptors, or GPCRs) activate complex signaling networks and can adopt multiple active conformations upon agonist binding. As a consequence, the efficacy of receptors, which was classically considered linear, is now recognized as pluridimensional. Biased agonists selectively stabilize only a subset of receptor conformations induced by the natural unbiased ligand, thus preferentially activating certain signaling mechanisms. Such agonists thus reveal the intriguing possibility that one can direct cellular signaling with unprecedented precision and specificity and support the notion that biased agonists may identify new classes of therapeutic agents that have fewer side effects. This review focuses on one particular class of biased ligands that has the ability to alter the balance between G protein-dependent and beta-arrestin-dependent signal transduction.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available