Levoketoconazole

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

Clinical data
Trade names	Recorlev
Other names	COR-003; (2S,4R)-ketoconazole; NormoCort
License data	US DailyMed: Levoketoconazole
Routes of administration	By mouth
ATC code	H02CA04 (WHO)
Legal status
Legal status	US: ℞-only[1]
Identifiers
IUPAC name 1-[4-(4-{[(2S,4R)-2-(2,4-Dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)-1-piperazinyl]ethanone
CAS Number	142128-57-2
PubChem CID	47576
DrugBank	DB05667
ChemSpider	43284
UNII	2DJ8R0NT7K
KEGG	D10950
ChEBI	CHEBI:47518
ChEMBL	ChEMBL295698
PDB ligand	KLN (PDBe, RCSB PDB)
CompTox Dashboard (EPA)	DTXSID60161949
Chemical and physical data
Formula	C26H28Cl2N4O4
Molar mass	531.43 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC(=O)N1CCN(CC1)c2ccc(cc2)OC[C@@H]3CO[C@@](O3)(Cn4ccnc4)c5ccc(cc5Cl)Cl
InChI InChI=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 Key:XMAYWYJOQHXEEK-ZEQKJWHPSA-N

Levoketoconazole is the levorotatory or (2S,4R) enantiomer of ketoconazole,^[3][4][5] and it is an inhibitor of the enzymes CYP11B1 (11β-hydroxylase), CYP17A1 (17α-hydroxylase/17,20-lyase), and CYP21A2 (21-hydroxylase).^[2][3][5] It inhibits glucocorticoid biosynthesis and hence circulating levels of glucocorticoids, thereby treating Cushing's syndrome.^[2][5] 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.^[5] 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]

Research

In a systematic review of levoketoconazole, published in 2024, it was found to be effective in the management of Cushing Syndrome.^[9]