Figure 1.2.

Allosteric ligands can show a range of efficacies as modulators of agonist activity. Displayed are CRCs for hypothetical compounds “A” and “B” that act at a G_s-coupled receptor. (A) One of the standard assays for measuring activity of G_s-coupled receptors is the accumulation of cAMP, and for these compounds, A appears to be a robust PAM at this receptor while compound B appears to be essentially inactive. However, in a β-arrestin recruitment assay (B), both compounds robustly potentiate the agonist’s recruitment of β-arrestin to the receptor, indicating that compound B is an example of a β-arrestin-biased PAM. Having both datasets in hand allows for a more complete understanding of the pharmacology of individual compounds.