Levoketoconazole, sold under the brand name Recorlev, is a steroidogenesis inhibitor that is used for the treatment of Cushing's syndrome. Levoketoconazole was approved for medical use in the United States in December 2021. Levoketoconazole is the

levorotatory Optical rotation, also known as polarization rotation or circular birefringence, is the rotation of the orientation of the plane of polarization about the optical axis of linearly polarized light as it travels through certain materials. Circul ...

or (2''S'',4''R'')

enantiomer In chemistry, an enantiomer ( /ɪˈnænti.əmər, ɛ-, -oʊ-/ ''ih-NAN-tee-ə-mər''; from Ancient Greek ἐνάντιος ''(enántios)'' 'opposite', and μέρος ''(méros)'' 'part') – also called optical isomer, antipode, or optical ant ...

ketoconazole Ketoconazole, sold under the brand name Nizoral among others, is an antiandrogen and antifungal medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin infections such as tinea, cutaneous candid ...

, and it is an

inhibitor Inhibitor or inhibition may refer to: In biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotra ...

of the enzymes CYP11B1 (11β-hydroxylase), CYP17A1 (17α-hydroxylase/17,20-lyase), and

CYP21A2 Steroid 21-hydroxylase (also known as steroid 21-monooxygenase, cytochrome P450C21, 21α-hydroxylase and less commonly 21β-hydroxylase) is an enzyme that hydroxylates steroids at the C21 position and is involved in biosynthesis of aldosteron ...

(21-hydroxylase). It inhibits glucocorticoid

biosynthesis Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. ...

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 7 alpha-hydroxylase also known as cholesterol 7-alpha-monooxygenase or cytochrome P450 7A1 (CYP7A1) is an enzyme that in humans is encoded by the gene which has an important role in cholesterol metabolism. It is a cytochrome P450 enz ...

(cholesterol 7α-hydroxylase), theoretically resulting in further reduced interference with

bile acid Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver. Bile acids are conjugated with taurine or glycine residues to give anions called bile salts. Primary b ...

production and

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

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 (CYP51A1) is the animal version of a cytochrome P450 enzyme that is involved in the conversion of lanosterol to 4,4-dimethylcholesta-8(9),14,24-trien-3β-ol. The cytochrome P450 isoenzymes are a conserved group of pr ...

(lanosterol-14α-demethylase), similarly but more potently relative to ketoconazole.

References

External links

* * * {{Portal bar , Medicine 7α-Hydroxylase inhibitors 11β-Hydroxylase inhibitors 21-Hydroxylase inhibitors Acetamides Antiglucocorticoids Chloroarenes Cholesterol side-chain cleavage enzyme inhibitors CYP3A4 inhibitors CYP17A1 inhibitors Dioxolanes Enantiopure drugs Lanosterol 14α-demethylase inhibitors para-Methoxyphenylpiperazines Phenylethanolamine ethers