• Louis M Luttrell.
• Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.
• Prog Mol Biol Transl Sci. 2013 Jan 1; 118: 469-97.

AbstractOur growing appreciation of the pluridimensionality of G protein-coupled receptor (GPCR) efficacy, coupled with the phenomenon of orthosteric ligand "bias," offers the prospect of drugs that selectively modulate different aspects of GPCR function for therapeutic benefit. As the best-studied non-G protein effectors, arrestins have been shown to mediate a wide range of GPCR signals, and arrestin pathway-selective ligands have been identified for several receptors. When viewed from the perspective of short term in vitro assays, such "biased" agonists appear to activate a subset of the response profile produced by a conventional agonist. Yet, when examined in vivo, the limited data available suggest that biased ligand effects can diverge from their conventional counterparts in ways that cannot be predicted from their in vitro efficacy profile. While some widely conserved arrestin-regulated biological processes are becoming apparent, what is lacking at present is a rational framework for relating the in vitro efficacy of a "biased" agonist to its in vivo actions that will aid drug discovery programs in identifying "biased" ligands with the desired biological effects.Copyright © 2013 Elsevier Inc. All rights reserved.

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