Levoketoconazole



























































Levoketoconazole
Levoketoconazole.svg
Clinical data
Trade names Recorlev
Synonyms COR-003; (2S,4R)-ketoconazole; NormoCort
Routes of
administration		 By mouth
Identifiers
CAS Number
  • 142128-57-2

PubChem CID
  • 47576
ChemSpider
  • 43284
UNII
  • 2DJ8R0NT7K
KEGG
  • D10950
Chemical and physical data
Formula
C26H28Cl2N4O4
Molar mass 531.4372 g/mol
3D model (JSmol)
  • Interactive image

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 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



  • List of investigational hormonal agents § Glucocorticoidics

  • Osilodrostat



References





  1. ^ abcd http://adisinsight.springer.com/drugs/800037965


  2. ^ abcd 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..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output .citation q{quotes:"""""""'""'"}.mw-parser-output .citation .cs1-lock-free a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .citation .cs1-lock-limited a,.mw-parser-output .citation .cs1-lock-registration a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .citation .cs1-lock-subscription a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-ws-icon a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/4/4c/Wikisource-logo.svg/12px-Wikisource-logo.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{font-size:100%}.mw-parser-output .cs1-maint{display:none;color:#33aa33;margin-left:0.3em}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}


  3. ^ abc 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. ^ abcdef 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.


  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




External links


  • Levoketoconazole - AdisInsight










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