Levoketoconazole, the 2S,4R Enantiomer of Ketoconazole, a New Steroidogenesis Inhibitor for Cushing’s Syndrome Treatment

Abstract Introduction Racemic ketoconazole (RK) is a steroidogenesis inhibitor used for treatment of Cushing’s syndrome. Levoketoconazole (COR-003), the pure 2S,4R enantiomer, potentially more potent and safe compared to RK. We in vitro effects levoketoconazole RK on adrenocortical pituitary adenoma cells. Materials methods HAC15 cells 15 primary human neoplastic cultures (+/− ACTH), murine (AtT20) corticotroph were incubated with or (0.01-10 µM). Cortisol ACTH measured using chemiluminescence immunoassay system, steroid profiles by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results In HAC15, inhibited cortisol at lower concentrations (IC50: 0.300 µM) (0.611 µM; P < 0.0001). IC50 values basal production varied over 24-fold range (0.00578-0.140 µM), 2 patients having higher sensitivity vs (2.1- 3.7-fold). LC-MS/MS analysis selected cases revealed inhibition other profile components AtT20, cell growth secretion (10 µM: −54% −38%, respectively), number 1 (−44%, 0.001). Conclusion potently inhibits cells, variable degree suppression between specimens. adrenal might also inhibit Together previously reported potential advantages, this indicates that promising novel pharmacotherapy