Beta-arrestin-biased ligands at seven-transmembrane receptors

Trends Pharmacol Sci. 2007 Aug;28(8):416-22. doi: 10.1016/ Epub 2007 Jul 20.


Seven-transmembrane receptors (7TMRs), the most common molecular targets of modern drug therapy, are critically regulated by beta-arrestins, which both inhibit classic G-protein signaling and initiate distinct beta-arrestin signaling. The interplay of G-protein and beta-arrestin signals largely determines the cellular consequences of 7TMR-targeted drugs. Until recently, a drug's efficacy for beta-arrestin recruitment was believed to be proportional to its efficacy for G-protein activities. This paradigm restricts 7TMR drug effects to a linear spectrum of responses, ranging from inhibition of all responses to stimulation of all responses. However, it is now clear that 'biased ligands' can selectively activate G-protein or beta-arrestin functions and thus elicit novel biological effects from even well-studied 7TMRs. Here, we discuss the current state of beta-arrestin-biased ligand research and the prospects for beta-arrestin bias as a therapeutic target. Consideration of ligand bias might have profound influences on the way scientists approach 7TMR-targeted drug discovery.

Publication types

  • Review

MeSH terms

  • Allosteric Regulation
  • Animals
  • Arrestins / chemistry
  • Arrestins / metabolism
  • Arrestins / pharmacology*
  • Drug Design
  • Humans
  • Ligands*
  • Models, Biological
  • Protein Binding
  • Receptors, G-Protein-Coupled / chemistry
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction / drug effects*
  • beta-Arrestins


  • Arrestins
  • Ligands
  • Receptors, G-Protein-Coupled
  • beta-Arrestins
  • seven-transmembrane G-protein-coupled receptor