Letrozole
(Synonyms: 来曲唑; CGS 20267) 目录号 : GC10726
Letrozole（来曲唑; CGS 20267）是一种口服活性非甾体类选择性芳香酶抑制剂，IC50为11.5nM。
Cas No.:112809-51-5
Sample solution is provided at 25 µL, 10mM.
Letrozole (CGS 20267) is an orally active nonsteroidal selective aromatase inhibitor with an IC50 of 11.5nM[1]. Letrozole prevents aromatase from producing estrogens by competitively and reversibly binding to the heme of its cytochrome P450 unit[2]. Letrozole is commonly used to treat certain types of breast cancer in postmenopausal women, including hormone receptor-positive breast cancer[3].
In vitro, Letrozole (100nM) treatment of breast cancer MCF7 cells for 72h significantly reduced the migration, invasion and adhesion of MCF7 cells when co-cultured with cancer-associated fibroblasts (CAFs), but had no effect on the proliferation of MCF7 cells[4]. Letrozole (10nM) treatment of breast cancer MCF7 cells for 24h and 48h significantly inhibited the levels of intracellular matrix metalloproteinases (MMPs) and also inhibited the stimulatory effect of testosterone on the proliferation of MCF7 cells[5].
In vivo, oral administration of Letrozole (1, 2.5mg/kg/day) to male Parkes mice for 28 days showed degenerative changes in the testicular histology of the mice, a significant decrease in the number of PCNA-positive germ cells in each seminiferous tubule in the testis, a significant increase in testosterone levels, but a significant decrease in estradiol levels[6]. Oral administration of Letrozole (0.5mg/kg/day) to rats with endometriosis for 3 weeks significantly reduced the size of the endometriosis, with a reduction percentage of 79.92% ± 7.89%[7].
References:
[1] Bhatnagar A S, Häusler A, Schieweck K, et al. Highly selective inhibition of estrogen biosynthesis by CGS 20267, a new non-steroidal aromatase inhibitor[J]. The Journal of steroid biochemistry and molecular biology, 1990, 37(6): 1021-1027.
[2] Miller W R, Bartlett J, Brodie A M H, et al. Aromatase inhibitors: are there differences between steroidal and nonsteroidal aromatase inhibitors and do they matter?[J]. The oncologist, 2008, 13(8): 829-837.
[3] Barnadas A, Estévez L G, Lluch-Hernández A, et al. An overview of letrozole in postmenopausal women with hormone-responsive breast cancer[J]. Advances in therapy, 2011, 28: 1045-1058.
[4] Li K, Kang H, Wang Y, et al. Letrozole-induced functional changes in carcinoma-associated fibroblasts and their influence on breast cancer cell biology[J]. Medical Oncology, 2016, 33: 1-11.
[5] Mitropoulou T N, Tzanakakis G N, Kletsas D, et al. Letrozole as a potent inhibitor of cell proliferation and expression of metalloproteinases (MMP‐2 and MMP‐9) by human epithelial breast cancer cells[J]. International journal of cancer, 2003, 104(2): 155-160.
[6] Verma R, Krishna A. Effect of Letrozole, a selective aromatase inhibitor, on testicular activities in adult mice: Both in vivo and in vitro study[J]. General and Comparative Endocrinology, 2017, 241: 57-68.
[7] Yarmolinskaya M, Molotkov A. Evaluation of the effectiveness of letrozole in the treatment of experimentally modeled endometriosis in rats[J]. Journal of Endometriosis and Pelvic Pain Disorders, 2019, 11(3): 126-131.
Letrozole（来曲唑; CGS 20267）是一种口服活性非甾体类选择性芳香酶抑制剂，IC50为11.5nM[1]。Letrozole通过与其细胞色素P450单元的血红素竞争性、可逆结合来防止芳香酶产生雌激素[2]。Letrozole通常用于治疗绝经后女性的某些类型的乳腺癌，包括激素受体阳性乳腺癌[3]。
在体外，Letrozole（100nM）处理乳腺癌MCF7细胞72h，在与癌相关成纤维细胞（CAFs）共培养的条件下，Letrozole显著降低了MCF7细胞的迁移、侵袭和粘附，但对MCF7细胞的增殖没有影响[4]。Letrozole（10nM）处理乳腺癌MCF7细胞24h和48h，显著抑制了细胞内基质金属蛋白酶（MMP）的水平，还抑制睾酮对MCF7细胞增殖的刺激作用[5]。
在体内，Letrozole（1, 2.5mg/kg/day）通过口服治疗雄性Parkes品系小鼠28天，小鼠睾丸组织学出现退行性改变，睾丸内每个曲细精管的PCNA阳性生殖细胞数量明显减少，睾酮水平明显升高，但雌二醇水平明显下降[6]。Letrozole（0.5mg/kg/day）通过口服治疗子宫内膜异位症大鼠3周，显著减小了异位症大小，减少百分比为79.92%±7.89%[7]。
| Cell experiment [1]: | |
Cell lines | MCF7 cells |
Preparation Method | 4×105 carcinoma-associated fibroblasts (CAFs) were seeded on a 10cm culture dish. After co-culturing with 2×105 MCF7 cells using a standing transwell with or without 100nM Letrozole for 72h, the upper chamber was removed, and the chambers were fixed in 4% formaldehyde for 30min and stained with 5% crystal violet for 5min. The cells that migrated or invaded to the lower surface of the membrane were counted from 6 randomized fields at 100 times magnifications using an inverted microscope. The assay was performed in triplicate. |
Reaction Conditions | 100nM;72h |
Applications | In the presence of CAFs, Letrozole significantly reduced the migration, invasion, and adhesion of MCF7 cells, but had no effect on the proliferation of MCF7 cells. |
| Animal experiment [2]: | |
Animal models | Male Parkes strain mice |
Preparation Method | Mice were randomly divided into three groups (n=10 per group). The Group 1 was control and received the vehicle (1% aqueous solution of carboxmethylcellulose). The Group 2 and 3 were experimental received low dose (1mg/kg) and high dose (2.5mg/kg) of Letrozole through oral gavage, for 28 days. At the end of the experiment, animals were killed by decapitation under a mild dose of anesthetic ether and blood was collected. Serum was collected from blood and kept at 20℃ for further assay. Testis of one side of each animal was kept at 20℃ for immunoblot and the other side of the testis was fixed in Bouin’s fluid for immunohistochemistry. |
Dosage form | 1, 2.5mg/kg/day for 28 days; p.o. |
Applications | The testicular histology of mice treated with Letrozole showed degenerative changes, the number of PCNA-positive germ cells per seminiferous tubule in the testis decreased significantly, and the testosterone level increased significantly, but the estradiol level decreased significantly. |
References: [1]Li K, Kang H, Wang Y, et al. Letrozole-induced functional changes in carcinoma-associated fibroblasts and their influence on breast cancer cell biology[J]. Medical Oncology, 2016, 33: 1-11. [2]Verma R, Krishna A. Effect of Letrozole, a selective aromatase inhibitor, on testicular activities in adult mice: Both in vivo and in vitro study[J]. General and Comparative Endocrinology, 2017, 241: 57-68. | |
| Cas No. | 112809-51-5 | SDF | |
| 别名 | 来曲唑; CGS 20267 | ||
| 化学名 | 4-[(4-cyanophenyl)-(1,2,4-triazol-1-yl)methyl]benzonitrile | ||
| Canonical SMILES | C1=CC(=CC=C1C#N)C(C2=CC=C(C=C2)C#N)N3C=NC=N3 | ||
| 分子式 | C17H11N5 | 分子量 | 285.3 |
| 溶解度 | ≥ 14.265mg/mL in DMSO | 储存条件 | Store at -20°C |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.5051 mL | 17.5254 mL | 35.0508 mL |
| 5 mM | 0.701 mL | 3.5051 mL | 7.0102 mL |
| 10 mM | 0.3505 mL | 1.7525 mL | 3.5051 mL |
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