Levoketoconazole

Levoketoconazole (INN, USAN) (developmental code name COR-003; tentative brand name Recorlev, previously NormoCort), also known as (2S,4R)-ketoconazole, is a steroidogenesis inhibitor that is under development by Strongbridge Biopharma (formerly Cortendo AB) for the treatment of Cushing's syndrome.[1][2][3][4] It is currently in phase III clinical trials for this indication.[1][2] The drug is the levorotatory or (2S,4R) enantiomer of ketoconazole.[2][3][4] It is expected to have greater potency, efficacy, and safety, including a lower risk of hepatotoxicity, relative to racemic ketoconazole.[3][4]

Levoketoconazole
Clinical data
Trade namesRecorlev
Other namesCOR-003; (2S,4R)-ketoconazole; NormoCort
Routes of
administration		By mouth
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
Chemical and physical data
FormulaC26H28Cl2N4O4
Molar mass531.4372 g/mol g·mol−1
3D model (JSmol)

Levoketoconazole is an inhibitor of the enzymes CYP11B1 (11β-hydroxylase), CYP17A1 (17α-hydroxylase/17,20-lyase), and CYP21A2 (21-hydroxylase).[1][2][4] It inhibits glucocorticoid biosynthesis and hence circulating levels of glucocorticoids, thereby treating Cushing's syndrome.[1][4] 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.[4] 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.[5]

See also

References
  1. http://adisinsight.springer.com/drugs/800037965
  2. Edward R. Laws Jr; Louise Pace (11 November 2016). Cushing's Disease: An Often Misdiagnosed and Not So Rare Disorder. Elsevier Science. pp. 113–. ISBN 978-0-12-804390-5.
  3. Eliza B. Geer (1 December 2016). The Hypothalamic-Pituitary-Adrenal Axis in Health and Disease: Cushing’s Syndrome and Beyond. Springer. pp. 170–. ISBN 978-3-319-45950-9.
  4. Cuevas-Ramos, Daniel; Lim, Dawn Shao Ting; Fleseriu, Maria (2016). "Update on medical treatment for Cushing's disease". Clinical Diabetes and Endocrinology. 2 (1). doi:10.1186/s40842-016-0033-9. ISSN 2055-8260. PMC 5471955.
  5. Thieroff-Ekerdt, R., Lavin, P., Abou-Gharbia, M., & France, N. (2016). Pharmacology of Cor-003 (levoketoconazole), an Investigational Treatment for Endogenous Cushing's Syndrome. In Pituitary Disorders-It's Not the Anterior Pituitary (posters) (pp. SAT-547). Endocrine Society. doi:10.1210/endo-meetings.2016.np.15.sat-547 https://www.strongbridgebio.com/wp-content/uploads/strongbridge-poster-pharmology-cor-003.pdf


This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.