Levoketoconazole Explained

Width:250px
Tradename:Recorlev
Dailymedid:Levoketoconazole
Routes Of Administration:By mouth
Atc Prefix:H02
Atc Suffix:CA04
Legal Us:Rx-only
Legal Us Comment:[1]
Cas Number:142128-57-2
Pubchem:47576
Drugbank:DB05667
Chemspiderid:43284
Unii:2DJ8R0NT7K
Kegg:D10950
Chebi:47518
Chembl:295698
Pdb Ligand:KLN
Synonyms:COR-003; (2S,4R)-ketoconazole; NormoCort
Iupac Name:1-[4-(4-<nowiki/>{[(2''S'',4''R'')-2-(2,4-Dichlorophenyl)-2-(1''H''-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-1-piperazinyl]ethanone
C:26
H:28
Cl:2
N:4
O:4
Smiles:CC(=O)N1CCN(CC1)c2ccc(cc2)OC[C@@H]3CO[C@@](O3)(Cn4ccnc4)c5ccc(cc5Cl)Cl
Stdinchi:1S/C26H28Cl2N4O4/c1-19(33)31-10-12-32(13-11-31)21-3-5-22(6-4-21)34-15-23-16-35-26(36-23,17-30-9-8-29-18-30)24-7-2-20(27)14-25(24)28/h2-9,14,18,23H,10-13,15-17H2,1H3/t23-,26-/m1/s1
Stdinchikey:XMAYWYJOQHXEEK-ZEQKJWHPSA-N

Levoketoconazole, sold under the brand name Recorlev, is a steroidogenesis inhibitor that is used for the treatment of Cushing's syndrome.[2] [3] [4] [5] Levoketoconazole was approved for medical use in the United States in December 2021.[6] [7]

Levoketoconazole is the levorotatory or (2S,4R) enantiomer of ketoconazole, and it 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.[8]

External links

Notes and References

  1. Web site: Recorlev- levoketoconazole tablet . DailyMed . 12 January 2022 . 20 February 2022.
  2. Web site: Levoketoconazole - Strongbridge Biopharma . AdisInsight . Springer Nature Switzerland AG .
  3. Book: Laws Jr ER, Pace L . Cushing's Disease: An Often Misdiagnosed and Not So Rare Disorder. 11 November 2016. Elsevier Science. 978-0-12-804390-5. 113–.
  4. Book: Geer, Eliza B. . vanc . The Hypothalamic-Pituitary-Adrenal Axis in Health and Disease: Cushing's Syndrome and Beyond. 1 December 2016. Springer. 978-3-319-45950-9. 170–.
  5. Cuevas-Ramos D, Lim DS, Fleseriu M . Update on medical treatment for Cushing's disease . Clinical Diabetes and Endocrinology . 2 . 1 . 16 . 2016 . 28702250 . 5471955 . 10.1186/s40842-016-0033-9 . free .
  6. Web site: Levoketoconazole: FDA-Approved Drugs . U.S. Food and Drug Administration (FDA) . 3 January 2022.
  7. Xeris Biopharma Announces U.S. FDA Approval of Recorlev (levoketoconazole) for the Treatment of Endogenous Hypercortisolemia in Adult Patients With Cushing's Syndrome . Xeris Biopharma . Business Wire . 30 December 2021 . 3 January 2022.
  8. Thieroff-Ekerdt R, Lavin P, Abou-Gharbia M, France N . Pharmacology of COR-003 (levoketoconazole), an investigational treatment for endogenous Cushing's syndrome. . Pituitary disorders—it’s not the anterior pituitary (posters) . SAT-547-SAT-547 . October 2016 . Endocrine Society . 30 April 2017 . 20 September 2020 . https://web.archive.org/web/20200920110042/https://www.strongbridgebio.com/wp-content/uploads/strongbridge-poster-pharmology-cor-003.pdf . dead .