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(Z)-4-Hydroxytamoxifen

现货
Catalog No.
B5421
雌激素受体(ER)调节剂
组合的产品项目
规格价格库存 数量
2mg
¥ 550.00
现货
5mg
¥ 1,100.00
现货
10mg
¥ 1,540.00
现货
25mg
¥ 3,300.00
现货

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Background

Estrogen receptors (ER) are members of the superfamily of ligand-modulated nuclear receptors that mediate the actions of steroid hormones, vitamin D, retinoids, and thyroid hormones. ER is activated in vivo when bound by naturally occurring estrogens such as 17α-estradiol. In addition to regulating these physiological processes, estrogen also plays a central role in stimulating breast cancer growth. (Z)-Tamoxifen is a first generation selective ER modulators that is currently approved by the FDA and is widely used to treat estrogen-dependent breast cancers. Its active metabolite, (Z)-4-Hydroxytamoxifen, is a potent estrogen receptor modulator.

In vitro: (Z)-4-hydroxytamoxifen binds to ER with 8-fold higher affinity than tamoxifen. It was found that only the Z isomer has the required antiestrogenic activity; the (E)-4-hydroxytamoxifen has only about 5% of its affinity for the ER [1].

In vivo: The antioestrogenic activities of (Z)-4-hydroxytamoxifen and tamoxifen were determined after oral administration. (Z)-4-hydroxytamoxifen was administered to groups of immature rats which also received s.c. injections of 0-2 μg oestradiol. Both compounds produced a dose-related decrease in uterine wet weight when compared with the oestradiol-treated controls. At a dose of 1 μg/day, the antiuterotrophic effects of (Z)-4-hydroxytamoxifen and tamoxifen were not significantly different but at 5μg/day, (Z)-4-hydroxytamoxifen was more active (P < 0.01). (Z)-4-hydroxytamoxifen therefore appears to retain its potent antioestrogenic activity after oral administration [2].

Clinical trial: Up to now, (Z)-4-Hydroxytamoxifen is still in the preclinical development stage.

Reference:
[1] Donna D.  Yu and Barry M. Forman. Simple and Efficient Production of (Z)-4-Hydroxytamoxifen, a Potent Estrogen Receptor Modulator. J. Org. Chem. 2003, 68, 9489-9491
[2] Jordan VC, Collins MM, Rowsby L, Prestwich G.  A monohydroxylated metabolite of tamoxifen with potent antioestrogenic activity. J Endocrinol. 1977 Nov;75(2):305-16.

Chemical Properties

StorageStore at -20°C
M.Wt387.51
Cas No.68047-06-3
FormulaC26H29NO2
Solubility≥38.8mg/mL in DMSO
Chemical Name(Z)-4-(1-(4-(2-(dimethylamino)ethoxy)phenyl)-2-phenylbut-1-en-1-yl)phenol
SDFDownload SDF
Canonical SMILESOC1=CC=C(C=C1)/C(C(C=C2)=CC=C2OCCN(C)C)=C(C3=CC=CC=C3)\CC
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1]:

细胞系

未成熟的大鼠垂体腺细胞

溶解方法

该化合物在DMSO中的溶解度大于10 mM。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。

反应条件

1-100 nM,6天

应用

(Z)-4-Hydroxytamoxifen抑制雌二醇刺激的PRL合成,其比tamoxifen更有效。

动物实验 [2]:

动物模型

未成熟大鼠

给药剂量

口服,5 μg/day

应用

在未成熟大鼠中,与雌二醇治疗的对照相比,皮下注射0-2 μg雌二醇、(Z)-4-hydroxytamoxifen以剂量依赖性方式降低子宫湿重。(Z)-4-hydroxytamoxifen(5 μg/天)显示抗营养作用。

注意事项

由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。

References:

[1]. JORDAN V C, KOCH R, LANGAN S, et al. Ligand interaction at the estrogen receptor to program antiestrogen action: a study with nonsteroidal compounds in vitro[J]. Endocrinology, 1988, 122(4): 1449-1454.

[2]. Jordan V C, COLLINS M M, ROWSBY L, et al. A monohydroxylated metabolite of tamoxifen with potent antioestrogenic activity[J]. Journal of Endocrinology, 1977, 75(2): 305-316.

质量控制

化学结构

(Z)-4-Hydroxytamoxifen