Journal
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 52
Volume 52, Issue -, Pages 153-178Publisher
ANNUAL REVIEWS
DOI: 10.1146/annurev-pharmtox-010611-134514
Keywords
allosteric modulation; biased agonism; bivalent ligand; drug discovery; functional selectivity; receptor theory
Categories
Ask authors/readers for more resources
It is now acknowledged that G protein-coupled receptors, the largest class of drug targets, adopt multiple active states that can be preferentially stabilized by orthosteric ligands or allosteric modulators, thus giving rise to the phenomenon of pathway-biased signaling. In the past few years, researchers have begun to explore the potential of linking orthosteric and allosteric pharmacophores to yield bitopic hybrid ligands. This approach is an extension of the more traditional bivalent ligand concept and shares some of the same challenges, including the choice and role of the linker between the two pharmacophores and the validation of mechanism of action. Nonetheless, the promise of bitopic ligands is the generation of novel chemical tools that have improved affinity and/or selectivity profiles. Previously identified functionally selective compounds (and medicines) also may act via a bitopic mechanism, suggesting that the phenomenon is more widespread than currently appreciated.
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