Hexestrol

Hexestrol (Bibenzyl) is a novel type of 17β-hydroxysteroid dehydrogenase, AKR1C1and AKR1C2 potent inhibitor with IC50 of 0.8, 9.5, 2.8 µM, respectively and exhibits strong affinity for estrogen receptors. It is a synthetic estrogen that has been used as a hormonal antineoplastic agent. Rat liver contains two cytosolic enzymes (TBER1 and TBER2). TBER1 represents a novel type of 17β-hydroxysteroid dehydrogenase with unique catalytic properties and tissue distribution.. The recombinant TBER1 efficiently oxidized 17β-hydroxysteroids and xenobiotic alicyclic alcohols using NAD+ as the preferred coenzyme at pH 7.4, and showed low activity towards 20α- and 3α-hydroxysteroids, and 9-hydroxyprostaglandins. The enzyme was potently inhibited by diethylstilbestrol, hexestrol and zearalenone. Rat 17HSD5 differed from TBER1 in inhibitor sensitivity. The inhibitory potencies of diethylstilbestrol (IC50 = 7.5 µM), hexestrol (IC50 = 30 µM), and zearalenone (IC50 = 36 µM) for 17HSD5 were lower than those for TBER1 (the respective IC50 values were 1.7, 0.8 and 7.5 µM).