Fig. 1

Mechanism of action of novel medical treatments for Cushing’s disease. From left to right: R-roscovitine induces cell cycle arrest, tumor shrinkage and reduction of ACTH synthesis and secretion. Exact mechanism of action is currently under study. Retinoic acid inhibits POMC expression, decreasing ACTH synthesis and release. An additional novel treatment under evaluation is the selective, peptide melanocortin-2 receptor (MC2R) antagonist that blocks ACTH action at the adrenal cortex. Osilodrostat is a steroidogenesis inhibitor that blocks the action of CYP11B1 and CYP11B2 (yellow X) with greater affinity than metyrapone. Levoketoconazole is a steroidogenesis inhibitor with greater potency than ketoconazole in blocking CYP11B1, CYP21 and CYP17 during cortisol synthesis (red X). Osilodrostat and levoketoconazole are currently being studied in phase III clinical trials