Levoketoconazole

Levoketoconazole (, ) (developmental code name COR-003; tentative brand name Recorlev, previously NormoCort), also known as (2"S",4"R")-ketoconazole, is a steroidogenesis inhibitor that is under development by Strongbridge Biopharma (formerly Cortendo AB) for the treatment of Cushing's syndrome. It is currently in phase III clinical trials for this indication. The drug is the levorotatory or (2"S",4"R") enantiomer of ketoconazole. It is expected to have greater potency, efficacy, and safety, including a lower risk of hepatotoxicity, relative to racemic ketoconazole.
Levoketoconazole is an inhibitor of the enzymes CYP11B1 (11β-hydroxylase), CYP17A1 (17α-hydroxylase/17,20-lyase), and CYP21A2 (21-hydroxylase). It inhibits glucocorticoid biosynthesis and hence circulating levels of glucocorticoids, thereby treating Cushing's syndrome. In addition to its increased potency, the drug is 12-fold less potent than racemic ketoconazole in inhibiting CYP7A1 (cholesterol 7α-hydroxylase), theoretically resulting in further reduced interference with bile acid production and metabolite elimination and therefore less risk of hepatotoxicity. Levoketoconazole has also been found to inhibit CYP11A1 (cholesterol side-chain cleavage enzyme) and CYP51A1 (lanosterol-14α-demethylase), similarly but more potently relative to ketoconazole.