Inhibition of 11β-HSD1 and 11β-HSD2 by compounds predicted by virtual screening.

11β-HSD1-dependent conversion of cortisone (200 nM cortisone, 500 µM NADPH) to cortisol was determined by incubating lysates of HEK-293 cells stably expressing the human enzyme in the presence of vehicle or 20 µM of the respective compound for 10 min at 37°C. Similarly, 11β-HSD2-dependent conversion of cortisol (50 nM cortisol, 500 µM NAD+) to cortisone was measured. Data represent mean ± SD from at least three independent experiments.
T0504 and fenofibrate were used as synthetic positive controls, glycyrrhetinic acid as natural product positive control. N.D., not detectable (complete inhibition).