title: Analyzing biased responses of GPCR ligands.
abstract: 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.
authors.affiliation: Department of Pharmacology, University of Montreal, 2900 Boulevard Edouard-Montpetit, Montreal, QC H3T 1J4, Canada; Ste-Justine Hospital Research Center, 3175 Chemin de la Côte-Sainte-Catherine, Montreal, QC H3T 1C5, Canada. Electronic address: besma.benredjem@umontreal.ca.
authors.forename: Besma
authors.initials: B
authors.lastname: Benredjem
authors.affiliation: Ste-Justine Hospital Research Center, 3175 Chemin de la Côte-Sainte-Catherine, Montreal, QC H3T 1C5, Canada; Department of Psychiatry, University of Montreal, 2900 Boulevard Edouard-Montpetit, Montreal, QC H3T 1J4, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Dallaire
authors.affiliation: Department of Pharmacology, University of Montreal, 2900 Boulevard Edouard-Montpetit, Montreal, QC H3T 1J4, Canada; Ste-Justine Hospital Research Center, 3175 Chemin de la Côte-Sainte-Catherine, Montreal, QC H3T 1C5, Canada; Department of Psychiatry, University of Montreal, 2900 Boulevard Edouard-Montpetit, Montreal, QC H3T 1J4, Canada. Electronic address: graciela.pineyro.filpo@umontreal.ca.
authors.forename: Graciela
authors.initials: G
authors.lastname: Pineyro
mesh_terms: D000818:Animals; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D008024:Ligands; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D008024:Ligands; D043562:Receptors, G-Protein-Coupled