Metyrapone

Metyrapone is an inhibitor of the cytochrome P450 (CYP) enzyme 11β-hydroxylase (IC50 = 7.83 µM), an enzyme involved in the final step of cortisol biosynthesis.1 It also induces Cyp1a1 and Cyp3a4 expression in rat hepatic microsomes and inhibits the activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in sheep liver microsomes.2,3,4 Metyrapone (150 mg/kg, s.c.) suppresses hypoxia-ischemia-induced increases in plasma corticosterone levels and seizures in rats.5 It also reduces ethanol consumption in alcohol high-preferring rats.6 Formulations containing metyrapone have been used in the diagnosis of adrenal insufficiency and the treatment of Cushing’s disease.WARNING This product is not for human or veterinary use.

An 11β-hydroxylase inhibitor

226.3

≥98%

Biochemicals/Small Molecule Inhibitors/Cytochrome P450/Sterol Biosynthesis

Formal_Name:2-methyl-1,2-di-3-pyridinyl-1-propanone;Synonyms:NSC 25265 SU 4885

O=C(C1=CN=CC=C1)C(C)(C)C2=CC=CN=C2

C14H14N2O

54-36-4

≥ 4 years

DMF: 30 mg/ml DMSO: 30 mg/ml Ethanol: 30 mg/ml PBS (pH 7.2): 5 mg/ml

1.Hays, S.J.,Tobes, M.C.,Gildersleeve, D.L., et al. Structure-activity relationship study of the inhibition of adrenal cortical 11β-hydroxylase by new metyrapone analogues. Journal of Medicinal Chemistry 27(1), 15-19 (1984).
2.Harvey, J.L.,Paine, A.J. and Wright, M.C. Disruption of endogenous regulator homeostasis underlies the mechanism of rat CYP1A1 mRNA induction by metyrapone. Biochemistry Journal 331(1), 273-281 (1998).
3.Paine, A.J.,Villa, P. and Hockin, L.J. Evidence that ligand formation is a mechanism underlying the maintenance of cytochrome P-450 in rat liver cell culture. Biochemistry Journal 188(3), 937-939 (1980).
4.Kamenicky, P.,Droumaquet, C.,Salenave, S., et al. Mitotane, metyrapone, and ketoconazole combination therapy as an alternative to rescue adrenalectomy for severe ACTH-dependent cushing’s syndrome. Journal of Clinical Endocrinology and Metabolism 96(9), 2796-2804 (2011).
5.Sigalas, P.D.,Garg, H.,Watson, S., et al. Metyrapone in treatment-resistant depression. Ther.Adv.Psychopharmacol. 2(4), 139-149 (2012).
6.Hellmich, H.L.,Rojo, D.R.,Micci, M.A., et al. Pathway analysis reveals common pro-survival mechanisms of metyrapone and carbenoxolone after traumatic brain injury. PLoS One 8(1), e53230 (2013).