Extended Data Fig. 6: Concentration–response curves and Schild plots of the inverse agonists UCSF7447 and UCSF3384 in cAMP assays.
From: Virtual discovery of melatonin receptor ligands to modulate circadian rhythms
a, b, d, e, Modulation of hMT1-mediated (a, d) or hMT2-mediated (b, e) inhibition of isoproterenol-stimulated cAMP in HEK293T cells by melatonin in the presence of UCSF7447 (a, b) or UCSF3384 (d, e) for a range of concentrations. Data are normalized to the effect of isoproterenol alone and are mean ± s.e.m. of three biologically independent experiments (n = 3) run in triplicate. c, f, Schild plots depicting the competitive antagonism of melatonin by UCSF7447 (c) and UCSF3384 (f). Schild analysis of hMT1 (purple) and hMT2 (teal) show the competitive antagonism of UCSF7447 (hMT1, pKB = 7.4 ± 0.1, slope = 0.98 ± 0.03; hMT2, pKB = 6.2 ± 0.1, slope = 1.3 ± 0.4) (c) and UCSF3384 (hMT1, pA2 = 7.9 ± 0.1, slope = 0.80 ± 0.04; hMT2 pKB = 6.7 ± 0.1, slope = 1.0 ± 0.1) (f). Data are mean ± s.e.m. of three biologically independent experiments (n = 3) run in triplicate.
