Fadrozole (hydrochloride) (Synonyms: CGS 16949A)

Fadrozole is a non-steroidal aromatase inhibitor (IC50s = 5 and 1.4 nM for human placental and rat ovarian microsomal aromatase, respectively). It selectively inhibits estrogen over progesterone production induced by luteinizing hormone (LH) in hamster ovarian tissue as well as corticosterone and aldosterone production induced by adrenocorticotropic hormone in rat adrenal tissue (IC50s = 0.03, 160, 100, and 1 μM, respectively). It also decreases ovarian estrogen levels in rats when administered at a dose of 0.26 mg/kg. Fadrozole inhibits conversion of cholesterol to 27-hydroxycholesterol by the cytochrome P450 (CYP) isomer 27A1 (Ki = 4.6 μM). It inhibits growth of androstenedione-stimulated mammary D2 cells implanted into thoracic mammary fat pads of mice by 95% when administered at a dose of 0.5 mg per animal per day.

References:
[1]. Bhatnagar, A.S., H?usler, A., Schieweck, K., et al. Highly selective inhibition of estrogen biosynthesis by CGS 20267, a new non-steroidal aromatase inhibitor J. Steroid Biochem. Mol. Biol. 37(6), 1021-1027 (1990).
[2]. Steele, R.E., Mellor, L.B., Sawyer, W.K., et al. In vitro and in vivo studies demonstrating potent and selective estrogen inhibition with the nonsteroidal aromatase inhibitor CGS 16949A Steroids 50(1-3), 147-161 (1987).
[3]. Mast, N., Lin, J.B., and Pikuleva, I.A. Marketed drugs can inhibit cytochrome P450 27A1, a potential new target for breast cancer adjuvant therapy Mol. Pharmacol. 88(3), 428-436 (2015).
[4]. Tekmal, R.R., and Durgam, V.R. A novel in vitro and in vivo breast cancer model for testing inhibitors of estrogen biosynthesis and its action using mammary tumor cells with an activated int-5/aromatase gene Cancer Lett. 118(1), 21-28 (1997).