Figure 2. Discovery of a novel G_i/o-biased μOR agonist.

a, Compound 12 was identified among a series of analogues to compound 7 and further investigated due to its μOR specificity and efficacy as a μOR agonist. b, Docking pose of Compound 12. c, Compound 12 is a μOR agonist in a G_i/o signalling assay with an EC₅₀ of 180 nM. DAMGO is a prototypical unbiased opioid agonist. d, Despite robust activation of G_i/o, compound 12 induces minimal arrestin recruitment as compared to DAMGO. For c, d, data are mean ± s.e.m. of normalized results (n = 3–6 measurements).