Extended Data Figure 5. PZM21 is selective for μOR.

a, Compound PZM21 was screened against 320 non-olfactory GPCRs for agonism in the arrestin recruitment TANGO assay. Each point shows luminescence normalized to basal level at a given GPCR, with vertical lines indicating the standard error of the mean. b, GPCRs for which PZM21 induces an increase in signal twofold over background were further tested in full dose–response mode. Several potential targets (GPR110, MCHR1R, PTGER1) did not show dose-dependent increase in signal and probably represent screening false positives. CXCR7 and SSTR4 did show dose-dependent signals at high concentrations of PZM21, and were further tested in non-arrestin signalling assays. c, PZM21 does not show a dose-dependent change in cAMP inhibition in a G_i/o Glosensor assay measuring SSTR4 activation, indicating that the single elevated point in b is probably a false positive result. d, e, Inhibition assays of hERG (d) and the dopamine transporter (DAT), norepinephrine transporter (NET), and serotonin transporter (SERT) (e) show that PZM21 has weak inhibitory activity ranging from 2–34 μM at these targets. For a, data are mean ± s.e.m. of non-normalized results (n = 4 measurements). For b–e, data are mean ± s.e.m. of normalized results (n = 3–6 measurements).