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3β-hydroxysteroid dehydrogenase (3β-HSD) type 1 and type 2 isoforms are key enzymes for the biosynthesis of all active steroid hormones. 3β-HSD1 (type I) is expressed in placenta and peripheral tissues including breast tumors, whereas 3β-HSD2 (type 2) is expressed in the adrenal gland, ovary, and testis. Trilostane is an inhibitor of the 3β-HSDs: 3β-HSD1 and 3β-HSD2 with Ki values of 0.10 and 1.60 μM, respectively. Trilsotane has been approved for use in the treatment of Cushing’s syndrome in dogs to reduce cortisol, aldosterone, and corticosterone levels. Because human 3β-HSD (type 1) is a critical enzyme in the conversion of DHEA to estradiol in breast tumors, trilostane is also of interest for the treatment of breast cancer in postmenopausal women.
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