TABLE 2
Selectivity profiling of AC-45594 and analogs
Compounds were tested for activity at several nuclear receptors using R-SAT. Data from agonist experiments are reported as efficacy (% Eff) and potency (pEC50 = −Log[EC50]), relative to a standard reference. Antagonist and inverse agonist data are reported as pKi (−Log[Ki]) and pIC50 (−Log[IC50]), respectively. Efficacy and inhibition values were normalized to that of the reference drug defined as 100%: for SF-1 inverse, AC-45594; for LRH1, inhibition was normalized to the dynamic range of the constitutive activity displayed by LRH1 because no reference ligand is available; for ERα and ERα agonism, estrone (pEC50: ERα, 9.9 ± 0.4; ERβ 9.8 ± 0.3); for ERα and ERβ antagonism. 4OH-tamoxifen (pKi: ERα, 8.6 ± 0.2; ERβ, 9.1 ± 0.3). Potencies for the reference compounds were consistent with published literature values. Data are the average of several experiments performed in triplicates.