A CYP26A1 inhibitor
Liarozole is an inhibitor of the cytochrome P450 (CYP) isoform CYP26A1 (IC50 = 2.1 ?M), an enzyme involved in the metabolism of all-trans retinoic acid .1 It also inhibits the production of estradiol induced by follicle-stimulating hormone (FSH) in rat granulosa cells and testosterone and androstenedione production induced by human chorionic gonadotropin (hCG) in rat testicular cells (IC50s = 0.4, 2.3, and 0.7 ?M, respectively).2 Liarozole enhances the antiproliferative activity of all-trans retinoic acid in MCF-7 breast cancer cells.3 It decreases plasma levels of retinoic acid in rats in a dose-dependent manner.4 Liarozole (5 and 20 mg/kg) decreases estradiol undecylate-induced vaginal keratinization in ovariectomized rats.
1.Thatcher, J.E., Buttrick, B., Shaffer, S.A., et al.Substrate specificity and ligand interactions of CYP26A1, the human liver retinoic acid hydroxylaseMol. Pharmacol.80(2)228-239(2011) 2.Bruynseels, J., De Coster, R., Rooy, P.V., et al.R 75251, a new inhibitor of steroid biosynthesisProstate16(4)345-357(1990) 3.Wouters, W., van Dun, J., Dillen, A., et al.Effects of liarozole, a new antitumoral compound, on retinoic acid-induced inhibition of cell growth and on retinoic acid metabolism in MCF-7 human breast cancer cellsCancer Res.52(10)2841-2846(1992) 4.Van Wauwe, J., Van Nyen, G., Coene, M.C., et al.Liarozole, an inhibitor of retinoic acid metabolism, exerts retinoid-mimetic effects in vivoJ. Pharmacol. Exp. Ther.261(2)773-779(1992)
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