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Journal Article
Research Support, Non-U.S. Gov't
Review
Analyzing biased responses of GPCR ligands.
Current Opinion in Pharmacology 2017 Februrary
G protein-coupled receptors (GPCRs) are valuable targets for drug discovery. They exist in interconverting states differentially stabilized by diverse signaling partners. A ligand's capacity to distinguish among receptors associated with different partners is the basis of bias. This feature of GPCR signaling may allow development of ligands which specifically modulate effectors supporting desired actions. However, bias is time-dependent and cell-dependent such that in vitro bias may not predict bias displayed in vivo. Then again, certain signaling idiosyncrasies transcend these limitations and emerging signaling characteristics may be used to categorize ligands in terms of the signaling diversity, which is the other face of bias. Here, we discuss how time and cellular background influence magnitude/directionality of bias, and highlight approaches to categorize ligands according to signaling diversity.
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