Endoxifen
(Synonyms: Z-因多昔芬) 目录号 : GC12140
Endoxifen Z-异构体是最重要的他莫昔芬代谢物，负责在表达雌激素受体-α (ERα) 的乳腺癌细胞中引发该药物的抗雌激素作用。
Cas No.:112093-28-4
Sample solution is provided at 25 µL, 10mM.
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Endoxifen Z-isomer is the most important Tamoxifen metabolite responsible for eliciting the anti-estrogenic effects of this drug in breast cancer cells expressing estrogen receptor-alpha (ERα). Endoxifen inhibits hERG tail currents at 50 mV in a concentration-dependent manner with IC50 values of 1.6 μM.IC50 value: 1.6 μM [1]Target: hERG Potassium Channel, Estrogen Receptor/ERREndoxifen Z-isomer is considered a prodrug, since it has a much higher potency for the estrogen receptor than its parent drug. Endoxifen inhibits the hERG channel protein trafficking to the plasma membrane in a concentration-dependent manner with Endoxifen being more potent than Tamoxifen. [1] Endoxifen is also shown to be a more potent inhibitor of estrogen target genes when ERβ is expressed. Additionally, low concentrations of Endoxifen Z-isomer observed in Tamoxifen treated patients with deficient CYP2D6 activity (20 to 40 nM) markedly inhibit estrogen-induced cell proliferation rates in the presence of ERβ, whereas much higher Endoxifen Z-isomer concentrations are needed when ERβ is absent.[2]
References:
[1]. Chae YJ, et al. Endoxifen, the active metabolite of tamoxifen, inhibits cloned hERG potassium channels. Eur J Pharmacol. 2015 Apr 5;752:1-7.
[2]. Wu X, et al. Estrogen receptor-beta sensitizes breast cancer cells to the anti-estrogenic actions of endoxifen. Breast Cancer Res. 2011 Mar 10;13(2):R27.
Cell experiment: | MCF7 and Ishikawa cells are grown in 10% triple charcoal-stripped serum-containing medium for 3 d. The cells are then plated at a density of 2,000 cells per well in 96-well tissue culture plates and treated as indicated every 48 h. Cell proliferation assays are conducted 8 days after the first treatment using a CellTiter-Glo Luminescent Cell Viability kit[1]. |
Animal experiment: | Mice[2] GLAST::CreERT2 mice are used. Tamoxifen is injected as active metabolite 4-hydroxytamoxifen (4-OH-TAM), or 4-hydroxy-N-desmethyltamoxifen (Endoxifen). 4-OH-TAM is dissolved at 1 mM concentration in 2% ethanol/PBS and 5 μL injected into the ventricles. Endoxifen has not been used before for the induction of the ERT2 system. Endoxifen hydrochloride hydrate has a recommended solubility of over 10 mg/mL (25 mM) in 100% DMSO, corresponding to a maximum concentration of 25 mM or a dose of 125 nmol in a 5 μL volume. At this concentration, a proportion of mice developed neurological signs suggestive of neurotoxicity. Subsequently, concentrations of 2.5, 5, 10, 12.5 and 25 mM, dissolved in 10, 20, 40, 50 and 100% DMSO, respectively, corresponding to a drug dose of 12.5, 25, 50, 62.5 and 125 nmol are used. For testing DMSO toxicity, groups of three mice are injected with 5 uL PBS, 50% DMSO in PBS or 100% DMSO in PBS. Mice are culled 9 days after injection and coronally sectioned brains are stained for cleaved caspase 3, GFAP and Iba1. |
References: [1]. Wu X, et al. The tamoxifen metabolite, Endoxifen, is a potent antiestrogen that targets estrogen receptor alpha fordegradation in breast cancer cells. Cancer Res. 2009 Mar 1;69(5):1722-7. | |
| Cas No. | 112093-28-4 | SDF | |
| 别名 | Z-因多昔芬 | ||
| 化学名 | (Z)-4-(1-(4-(2-(methylamino)ethoxy)phenyl)-2-phenylbut-1-en-1-yl)phenol | ||
| Canonical SMILES | OC1=CC=C(C=C1)/C(C(C=C2)=CC=C2OCCNC)=C(C3=CC=CC=C3)\CC | ||
| 分子式 | C25H27NO2 | 分子量 | 373.49 |
| 溶解度 | ≥ 37.3mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.6774 mL | 13.3872 mL | 26.7745 mL |
| 5 mM | 0.5355 mL | 2.6774 mL | 5.3549 mL |
| 10 mM | 0.2677 mL | 1.3387 mL | 2.6774 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet