Aromatase (IC50 = 6 nM)

当暴露于盐酸法屈唑时，大鼠卵巢和人胎盘均表现出强烈的芳香酶抑制作用。 Fadrozole salty 的 IC50 为 0.03 μM，可抑制仓鼠卵巢切片中雌激素的合成。抑制孕酮产生的 IC50 值为 120 μM。高剂量的盐酸法屈唑可以在不同程度上抑制额外的细胞色素 P-450 依赖性激素的产生。 [1]。

在未成熟雌性大鼠中，口服法屈唑可抑制雄烯二酮介导的芳香酶产生的子宫肥大，ED50为0.03 mg/kg。对同一只小鼠口服氨基鲁米特产生了相同的结果，ED50 为 30 mg/kg [1]。在雌性斯普拉格-道利大鼠中，盐酸法屈唑可抑制自发性乳腺肿瘤的生长，包括恶性和良性肿瘤。此外，它可以减少雄性和雌性大鼠自发性肝肿瘤的发生频率，并减缓雌性大鼠垂体瘤的自发发育[2]。 Fadrozole 给予雄性和雌性小鼠，可减少 70% 的寄生虫负担，同时抑制 17b-雌二醇的生成。在雄性小鼠中，这种防御与特定细胞免疫反应的恢复有关。脾细胞中白细胞介素 6 (IL-6) 的产生和血清水平增加了 80%，而雄性感染小鼠睾丸中白细胞介素 6 (IL-6) 的表达增加了十倍。法屈唑治疗使这些水平恢复到初始水平[3]。

对于体外试验，将培养级Fadrozole 溶解在cRPMI中至所需的原液浓度，并通过0.2 mm Millipore过滤器进行灭菌。实验设计如下:采用24孔培养板，6孔作为未处理对照，6孔补充稀释Fadrozole 的培养液，6孔用不同浓度Fadrozole 处理。Fadrozole 的浓度随机分布在不同的盘子上。Fadrozole 制至终体积为100 μl，每孔加入2 ml培养基。对照囊肿用Fadrozole 稀释后的溶剂处理，每孔加入等体积的溶剂(100 μl)。繁殖以每个囊肿在处理后产生的芽的数量来测量，并在光学倒置显微镜下直接计数。囊肿的发病表现为内部组织逐渐紊乱，细胞质中出现朗讯区，运动能力逐渐丧失。死囊肿外观不透明，被盖细胞质内有透光区，并伴有特征性肿胀。生存能力是基于粒度，身体扭曲和亚甲基蓝吸收。当未染色的囊肿缺乏运动性和/或呈特征性颗粒状时，认为已死亡。所有存活观察都是在显微镜下进行的，基于前部和后部完全失去运动能力，以及内部失去食物摄入的运动能力，认为囊肿死亡。这些观察是在倒置显微镜下使用10倍和100倍的放大倍率进行的。[3]

Fadrozole was administered in the form of sub-dermal long-term release pellets (20 mg/wt kg, in three-week-release pellets), starting 1 week prior to the infection, using a 10-gauge needle Trochar. Three pellets were administrated during the study. Placebo pellets were administered to another group of infected mice, in the same fashion as the inhibitor. After 1 week, mice were infected as described above and killed 8 weeks later.[3]

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Rats are treated with daily dosing with fadrozole hydrochloride (CGS 16949A) in purified water by gavage for 2 years. There are 60 rats in each of four groups given 0, 0.05, 0.25 or 1.25 mg/kg daily. Control rats receive only water. Clinical signs are recorded weekly and the animals are examine for palpable masses every 4 weeks for the first 9 months, then every 2 weeks for the remainder of the study[2]. Mice: Fadrozole is administered in the form of sub-dermal long-term release pellets (20 mg/wt kg, in three-week-release pellets), starting 1 week prior to the infection, using a 10-gauge needle. Three pellets are administrated during the study. Placebo pellets are administered to another group of infected mice, in the same fashion as the inhibitor. After 1 week, mice are infected and killed 8 weeks later[3].

[1]. Fadrozole hydrochloride: a potent, selective, nonsteroidal inhibitor of aromatase for the treatment of estrogen-dependent disease. J Med Chem. 1991 Feb;34(2):725-36.

[2]. Prevention of spontaneous tumours in female rats by fadrozole hydrochloride, an aromatase inhibitor. Br J Cancer. 1995 Jul;72(1):72-5.

[3]. Inhibition of p-450 aromatase prevents feminisation and induces protection during cysticercosis. Int J Parasitol. 2002 Oct;32(11):1379-87.

Description
4-(5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-5-yl)benzonitrile is an imidazopyridine.
Fadrozole is a nonsteroidal aromatase inhibitor fadrozole with potential antineoplastic activity. Fadrozole specifically inhibits aromatase, blocking the aromatization of androstenedione and testosterone into estrone and estradiol, respectively, the final step in estrogen biosynthesis; the reduction in estrogen levels may inhibit growth in estrogen-dependent cancers. Aromatase, a member of the cytochrome P-450 superfamily, is found in many tissues; overexpression has been linked to the development of preneoplastic and neoplastic changes in breast tissue.
A selective aromatase inhibitor effective in the treatment of estrogen-dependent disease including breast cancer.

C14H13N3

223.27312

223.11

C, 75.31; H, 5.87; N, 18.82

102676-47-1

Fadrozole hydrochloride;102676-31-3;Dexfadrostat;102676-87-9;Fadrozole hydrochloride hemihydrate;176702-70-8;;102676-47-1; 2743427-54-3 (phosphate)

59693

White to off-white solid powder

1.2±0.1 g/cm3

481.7±38.0 °C at 760 mmHg

0ºC

245.1±26.8 °C

0.0±1.2 mmHg at 25°C

1.662

1.88

41.61

0

2

1

17

311

0

CLPFFLWZZBQMAO-UHFFFAOYSA-N

InChI=1S/C14H13N3/c15-8-11-4-6-12(7-5-11)14-3-1-2-13-9-16-10-17(13)14/h4-7,9-10,14H,1-3H2

4-(5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-5-yl)benzonitrile

Fadrozole; CGS 16949A; CGS-16949A; CGS16949A; 102676-47-1; 4-(5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-5-yl)benzonitrile; CGS-16949A; Fadrozole [INN]; Benzonitrile, 4-(5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-5-yl)-; CHEMBL9298; FAD 286A; Fadrozole free base

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 100 mg/mL (~447.89 mM)

配方 1 中的溶解度: ≥ 2.17 mg/mL (9.72 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 21.7 mg/mL澄清DMSO储备液加入400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.17 mg/mL (9.72 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 21.7 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.17 mg/mL (9.72 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 21.7 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。