Trilostane

Trilostane is an inhibitor of the 3β-HSDs (3β-HSD1 and 3β-HSD2 with Ki values of 0.10 and 1.60 μM, respectively) which plays a role in adrenal steroid biosynthesis. 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. While Trilsotane has been approved for use in the treatment of Cushing’s syndrome in dogs to reduce cortisol, aldosterone and corticosterone levels, it is being investigated as a possible treatment for both breast cancer and prostate cancer to prevent the synthesis of estrogens and androgens from endogenous precursors. Trilostane has also anti-inflammatory and analgesic properties and systemic administration of trilostane directly affected peripheral and brain levels in neuroactive steroids and monoamine turnover, resulting in antidepressant activity.