＞98%

Store at -20°C

来曲唑；CGS 20267

白色或类白色粉末

DMSO : 28.5 mg/mL (100 mM)

Aromatase

Letrozole potently inhibits aromatase derived from a variety of different sources including human placental microsomes, particulate fractions of human breast cancer, rat ovarian microsomes, MCF-7 cells transfected with aromatase (MCF-7Ca), JEG-3 human choriocarcinoma cells , CHO cells, hamster ovarian tissue, and particulate fractions of human breast cancer with IC50 of 11, 2, 7, 0.07, 0.07, 1.4, 20 and 0.8 nM. In the non-cellular systems, the IC50 of letrozole is calculated to be 1-13 nM. Letrozole maximally inhibits estradiol production in vitro in LH-stimulated hamster ovarian tissue at 0.1 μM with an IC50 of 0.02 μM and does not significantly affect progesterone production up to 350 μM. In ACTH-stimulated rat adrenal tissue in vitro, aldosterone production is inhibited by with an IC50 of 210 μM. Letrozole inhibits growth of the MCF-7 epithelial breast cancer cells in a dose-dependent way with IC50 of 1 nM. Inhibition can be observesed even at the very low concentrations tested (0.1 nM). Treatment of normal MCF-12A epithelial cells with letrozole did not affect their growth even when high letrozole concentrations (100 nM) or prolonged culture times. Letrozole (10 nM) significantly suppressed the stimulatory effects of 4-androstene-3,17-dione (100 nM) or testosterone (100 nM) on MCF-7 cell proliferation. Concurrent administration of 17-β-estradiol with letrozole (10 nM) decreased the stimulatory effect of the enzymatic activity of MMP-2 and - 9 released by estradiol.

Letrozole inhibits aromatase in vivo with ED50 of 1-3 μg/kg p.o.. Letrozole displays anti-endocrine effects. Letrozole inhibits androstenedione-induced uterine hypertrophy in immature rats with ED50 of 1-3 μg/kg. In the adult female rat, Letrozole (0.3-1 mg/kg daily p.o., 14 days) completely interrupts ovarian cyclicity and reduces uterine weight and serum estradiol (E2) concentrations to a similar extent to that seen after ovariectomy. Letrozole induces dose-dependent regression of estrogen-dependent, 9,10-dimethylbenz-a-anthracene (DMBA)-induced mammary tumors in adult female rats. The ED50 for Letrozole is determined to be 10 - 30 µg/kg/day, with complete inhibition at a daily dose of 10 µg/day. Letrozole produces dose-dependent inhibition of tumor growth of MCF-7 cells transfected with human aromatase gene (MCF-7Ca) implanted athymic nude mice, with complete inhibition at 20 mg/kg per day p.o..

[1] Haynes BP, et al. J Steroid Biochem Mol Biol, 2003, 87(1), 35-45.
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[3] Brodie AM. J Steroid Biochem Mol Biol. 49:281-7 (1994).