4-Hydroxytamoxifen
(Synonyms: (E/Z)-4-羟基他莫昔芬; Afimoxifene) 目录号 : GC17803
4-hydroxytamoxifen 是他莫昔芬和选择性雌激素受体拮抗剂的主要代谢产物。
Cas No.:68392-35-8
Sample solution is provided at 25 µL, 10mM.
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4-hydroxytamoxifen is a major metabolite of tamoxifen and selective estrogen receptor antagonist. It potentiated the protective effects of estradiol against the MA-induced nigrostriatal DA depletion.[1] 4-Hydroxytamoxifen has the superoxide anion radical-scavenging activity, the antioxidative characteristics of 4-Hydroxytamoxifen can attenuate the MA-induced dopaminergic toxicity.[4]
In vitro, 4-Hydroxytamoxifen decreased the transcriptional activity of ERRγ by more than 75%, with an EC50 value of 2 μM.[5] In MPNST cells were treated with 8-12 μM 4-Hydroxytamoxifen after 48 hours, there has a concentration-dependent increase in caspase 3-like enzymatic activity. 4-Hydroxytamoxifen also triggers autophagic death in MPNST cells.[2] In vitro study it indicated that 10 or 2 μM 4-hydroxytamoxifen abolished the generation of action potentials and repolarized the membrane potential in rat pancreatic beta-cells stimulated by 16 mM glucose. 4-hydroxytamoxifen impairs beta-cell electrical and secretory activity by inhibiting calcium and anion channel currents.[6]
In vivo experiment it shown that αMHC-MerCreMer mice were treated 20 mg/kg 4-hydroxytamoxifen intraperitoneally for 5 consecutive days, neither cardiac function nor cardiac energetic status in αMHC-MerCreMer mice was disturbed. In addition, the injection of 40 mg/kg 4-hydroxytamoxifen also did not impair cardiac function.[3] In vivo efficacy test it demonstrated that treatment with 6 μg/0.1 mL/day subcutaneously of 4-Hydroxytamoxifen significantly mitigated MA-induced nigrostriatal DA and DOPAC depletions in both male and female mice.[4]
References:
[1].Yu L.,?et al.?(2002a)?Ovarian hormones do not attenuate methamphetamine-induced dopaminergic neurotoxicity in mice gonadectomized at 4 weeks postpartum.?Neuroendocrinology?75,?282–287.
[2].Kohli L, et al. 4-Hydroxytamoxifen induces autophagic death through K-Ras degradation. Cancer Res. 2013 Jul 15;73(14):4395-405.
[3].Heinen A, et al. 4-hydroxytamoxifen does not deteriorate cardiac function in cardiomyocyte-specific MerCreMer transgenic mice. Basic Res Cardiol. 2021 Feb 5;116(1):8.
[4].Kuo YM, et al. 4-Hydroxytamoxifen attenuates methamphetamine-induced nigrostriatal dopaminergic toxicity in intact and gonadetomized mice. J Neurochem. 2003 Dec;87(6):1436-43.
[5].Coward P, et al. 4-Hydroxytamoxifen binds to and deactivates the estrogen-related receptor gamma. Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8880-4.
[6].Best L. Inhibition of glucose-induced electrical activity by 4-hydroxytamoxifen in rat pancreatic beta-cells. Cell Signal. 2002 Jan;14(1):69-73.
4-hydroxytamoxifen 是他莫昔芬和选择性雌激素受体拮抗剂的主要代谢产物。它增强了雌二醇对MA诱导的黑质纹状体DA耗竭的保护作用。[1] 4-Hydroxytamoxifen具有超氧阴离子自由基清除活性，4-Hydroxytamoxifen的抗氧化特性可以减弱MA-诱导多巴胺能毒性。[4]
在体外，4-Hydroxytamoxifen 使 ERRγ 的转录活性降低了 75% 以上，EC50 值为 2 μM。[5] 在 MPNST 细胞中，用 8-12 μM 4 处理- 48 小时后，羟基他莫昔芬会出现 caspase 3 样酶活性的浓度依赖性增加。 4-羟基他莫昔芬还会引发 MPNST 细胞的自噬性死亡。[2] 体外研究表明，10 或 2 μM 4-羟基他莫昔芬可消除大鼠胰腺 β- 细胞中动作电位的产生并使膜电位复极化。 16 mM 葡萄糖刺激的细胞。 4-羟基三苯氧胺通过抑制钙和阴离子通道电流来损害 β 细胞的电活动和分泌活动。[6]
体内实验表明，αMHC-MerCreMer 小鼠连续 5 天腹膜内注射 20 mg/kg 4-羟基三苯氧胺，αMHC-MerCreMer 小鼠的心脏功能和心脏能量状态均未受到干扰。此外，注射40 mg/kg 4-羟基他莫昔芬也没有损害心脏功能。[3] 体内药效试验表明，皮下注射6 μg/0.1 mL/天的4-羟他莫昔芬显着减轻雄性和雌性小鼠中 MA 诱导的黑质纹状体 DA 和 DOPAC 耗竭。[4]
| Cell experiment [1]: | |
|
Cell lines |
Multiple myeloma cell lines |
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Preparation Method |
Multiple myeloma cell lines were treated for 48 hours with vehicle or various concentrations of 4-Hydroxytamoxifen (1-10 μmol/L). Cell cycle analysis was done after propidium iodide staining of ethanol-permeabilized cells. |
|
Reaction Conditions |
1-10 μmol/L;for 48 hours |
|
Applications |
G1-arrest and apoptosis induction of multiple myeloma cells after 4-Hydroxytamoxifen treatment. |
| Animal experiment [2]: | |
|
Animal models |
iCM-Akt1/2, iCM-Gsk3β or iCM-p38 mice aged 3–4 month |
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Preparation Method |
For knockout induction, iCM-Akt1/2, iCM-Gsk3β or iCM-p38 mice aged 3–4 month received 4-Hydroxytamoxifen intraperitoneally (20 mg/kg) for either 5, 7, or 10 consecutive days, respectively, and hearts were excised two weeks after the end of the 4-Hydroxytamoxifen treatment for western blot analysis of protein depletion. In addition, immunohistological stainings were performed of hearts from iCM-Akt1/2KO or WT mice two weeks after 5 day 4-Hydroxytamoxifen treatment. |
|
Dosage form |
20 mg/kg; for either 5, 7, or 10 consecutive days |
|
Applications |
Cardiomyocyte restricted gene deletion was initiated by intraperitoneal application of 20 mg/kg 4-Hydroxytamoxifen on 5, 7 or 10 consecutive days. Administration of 20 mg/kg 4-Hydroxytamoxifen for five consecutive days resulted in loss of both Akt1 and Akt2 in cardiomyocytes. |
|
References: [1]. Gauduchon J, et al. 4-Hydroxytamoxifen inhibits proliferation of multiple myeloma cells in vitro through down-regulation of c-Myc, up-regulation of p27Kip1, and modulation of Bcl-2 family members. Clin Cancer Res. 2005 Mar 15;11(6):2345-54. [2]. Heinen A, et al. 4-hydroxytamoxifen does not deteriorate cardiac function in cardiomyocyte-specific MerCreMer transgenic mice. Basic Res Cardiol. 2021 Feb 5;116(1):8. |
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| Cas No. | 68392-35-8 | SDF | |
| 别名 | (E/Z)-4-羟基他莫昔芬; Afimoxifene | ||
| 化学名 | (Z)-4-(1-(4-(2-(dimethylamino)ethoxy)phenyl)-2-phenylbut-1-en-1-yl)phenol | ||
| Canonical SMILES | OC1=CC=C(/C(C2=CC=C(OCCN(C)C)C=C2)=C(C3=CC=CC=C3)\CC)C=C1 | ||
| 分子式 | C26H29NO2 | 分子量 | 387.51 |
| 溶解度 | ≥ 42mg/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 | 2.5806 mL | 12.9029 mL | 25.8058 mL |
| 5 mM | 0.5161 mL | 2.5806 mL | 5.1612 mL |
| 10 mM | 0.2581 mL | 1.2903 mL | 2.5806 mL |
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动物数量 | 只 |
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2.
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