Summary
Vorozole, the (+)-(S)-isomer of a new triazole compound, is a potent and selective aromatase inhibitor.In vitro, the compound is over a thousandfold more active than aminoglutethimide.In vivo, the compound very potently inhibits ovarian, peripheral, and tumoral aromatase. Vorozole shows anin vitro selectivity margin of 10,000-fold for aromatase inhibition as compared to inhibition of other P450- and non-P450-dependent reactions. This selectivity was confirmed in the ratin vivo. Vorozole, like ovariectomy, almost completely reduces tumor growth in the DMBA-induced mammary carcinoma model in the rat.
In postmenopausal women, vorozole very potently inhibits peripheral conversion of androstenedione to estrone. After chronic administration, plasma estradiol levels are reduced while the levels of adrenal gluco- and mineralo-corticoids remain unchanged. Vorozole has excellent oral bioavailability and exerts linear, dose-proportional pharmacokinetics.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Wouters W, Van Ginckel R, Krekels M, Bowden C, De Coster R: Pharmacology of vorozole. J Steroid Biochem Molec Biol 44:617–621, 1993
Wouters W, De Coster R, Krekels MDWG, van Dun J, Beerens D, Haelterman C, Raeymaekers A, Freyne E, Van Gelder J, Venet M, Janssen PAJ: R76713, a new specific non-steroidal aromatase inhibitor. J Steroid Biochem 32:781–788, 1989
Vanden Bossche H, Willemsens G, Roels I, Bellens D, Moereels H, Coene M-C, Le Jeune L, Lauwers W, Janssen PAJ: R 76713 and enantiomers: selective, nonsteroidal inhibitors of the cytochrome P450-dependent oestrogen synthesis. Biochem Pharmacol 40:1707–1718, 1990
Krekels MDWG, Wouters W, De Coster R: Aromatase inhibition by R76713: a kinetic analysis in rat ovarian homogenates. Steroids 55:69–73, 1990
Wouters W, De Coster R, Beerens D, Doolaege R, Gruwez JA, Van Camp K, Van Der Pas H, van Herendael B: Potency and selectivity of the aromatase inhibitor R76713. A study in human ovarian, adipose stromal, testicular and adrenal cells. J Steroid Biochem 36:57–65, 1990
Krekels MDWG, Wouters W, De Coster R, Van Ginckel R, Leonaers A, Janssen PAJ: Aromatase in the human choriocarcinoma JEG-3: inhibition by R 76 713 in cultured cells and in tumors grown in nude mice. J Steroid Biochem Molec Biol 38:415–422, 1991
Wouters W, De Coster R, van Dun J, Krekels MDWG, Dillen A, Raeymaekers A, Freyne E, Van Gelder J, Sanz G, Venet M, Janssen M: Comparative effects of the aromatase inhibitor R76713 and of its enantiomers R83839 and R83842 on steroid biosynthesis in vitro and in vivo. J Steroid Biochem Molec Biol 37:1049–1054, 1990
Tuman RW, Morris DM, Wallace NH, Bowden CR: Inhibition of peripheral aromatization in the male cynomolgus monkey by a novel nonsteroidal aromatase inhibitor (R 76713). J Clin Endocrinol Metab 72:755–760, 1991
Krekels MDWG, Wouters W, Van Ginckel R, Janssens B, Callens M, De Coster R: Aromatase inhibition by R 83 842, the dextro-isomer of R 76 713, in JEG-3 choriocarcinoma grown in ovariectomized nude mice. J Steroid Biochem Molec Biol 41:761–764, 1992
De Coster R, Van Ginckel R, Callens MJL, Goeminne NKG, Janssens BLE: Antitumoral and endocrine effects of (+)-vorozole in rats bearing dimethylbenzanthracene-induced mammary tumors. Cancer Res 52: 1240–1244, 1992
van der Wall E, Donker TH, de Frankrijker E, Nortier HWR, Thijssen JHH, Blankenstein RA: Inhibition of thein vivo conversion of androstenedione to estrone by the aromatase inhibitor vorozole in healthy postmenopausal women. Cancer Res 53:4563–4566, 1993
Borms M, Bruynseels J, De Coster R, Janssen PAJ: R76713: a specific non-steroidal aromatase inhibitor. A pilot study in advanced postmenopausal breast cancer. Proceedings of the Fourth International Congress on Hormones and Cancer, Amsterdam, Sept 15–19, 1991, p 237
De Coster R, Bruynseels J, Snoeck E, Woestenborghs R, Wouters W, Tuman B, Bowden C, Borms M, Van Rooy P: Vorozole: preclinical and clinical pharmacology. Proceedings of Clinical Use of Aromatase Inhibitors: Current Data and Future Perspectives, Bologna, June 17–19, 1992, p. 52–53
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Wouters, W., Snoeck, E. & De Coster, R. Vorozole, a specific non-steroidal aromatase inhibitor. Breast Cancer Res Tr 30, 89–94 (1994). https://doi.org/10.1007/BF00682743
Issue Date:
DOI: https://doi.org/10.1007/BF00682743