4-Hydroxytamoxifen ((Z)-4-Hydroxytamoxifen) is an orally active, selective estrogen receptor modulator (SERM). 4-Hydroxytamoxifen ((Z)-4-Hydroxytamoxifen) induces CRISPR/Cas9 systems based on ER mediated nucleus translocation^[1][2][3][4].

4-Hydroxytamoxifen (Monohydroxytamoxifen) is a selective ostrogen receptor antagonist, with an IC₅₀ of 3.3 nM for the [³H]oestradiol binding to oestrogen receptor. 4-Hydroxytamoxifen (10, 100 nM) enables to inhibit the binding of [³H]oestradiol to the human 8 S oestrogen receptor^[1]. 4-Hydroxytamoxifen activates intein-linked inactive Cas9, reduces off-target CRISPR-mediated gene editing. In human cells, conditionally active Cas9s modify target genomic sites with up to 25-fold higher specificity than wild-type Cas9^[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

4-Hydroxytamoxifen (0.2, 1 and 5 μg/day, p.o.) causes a dose-related decrease in uterine wet weight of immature rats^[1]. 4-Hydroxytamoxifen (6 μg/0.1 mL sesame oil/day, s.c.) effectively attenuates methamphetamine-induced nigrostriatal dopamine depletions in bothsexes of intact and gonadectomized C57BL/6 J mice. 4-Hydroxytamoxifen does not alter the dopamine content levels in the striatum^[3].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

387.51

C₂₆H₂₉NO₂

68047-06-3

4-羟基他莫昔芬

Room temperature in continental US; may vary elsewhere.

DMSO : 125 mg/mL (322.57 mM; Need ultrasonic)

Ethanol : 20 mg/mL (51.61 mM; Need ultrasonic)

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, 6 months; -20°C, 1 month。-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。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.08 mg/mL (5.37 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (5.37 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

  Solubility: ≥ 2.08 mg/mL (5.37 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (5.37 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 3.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.08 mg/mL (5.37 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (5.37 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Jordan VC, et al. A monohydroxylated metabolite of tamoxifen with potent antioestrogenic activity. J Endocrinol. 1977 Nov;75(2):305-16.

  [2]. Davis KM, et al. Small molecule-triggered Cas9 protein with improved genome-editing specificity. Nat Chem Biol. 2015 May;11(5):316-8.

  [3]. 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.

  [4]. Zhang J, et al. Drug Inducible CRISPR/Cas Systems. Comput Struct Biotechnol J. 2019;17:1171-1177.

Cytosol (200 μL) is incubated for 30 min at 4°C with different concentrations of oestradiol, tamoxifen and (4-Hydroxytamoxifen) or dihydroxytamoxifen administered in 10 μL methanol. Control tubes are incubated with 10 μL methanol alone and non-specific binding is determined in a parallel incubation of cytosol (200 μL) with methanol (10 μL) containing DES (5 × 10⁶ M). [2,4,6,7-³H]Oestradiol solution (50 μL) in TED buffer is added to each tube to give a final concentration of 2 × 10^-9 M. Incubation is continued for 4 h (4°C) and then 400 μL of a suspension of dextran-coated charcoal (250 mg % Norit A, 2.5 mg % dextran) in TED buffer are added and allowed to stand for 20 min. Tubes are centrifuged at 800 g for 10 min (4°C) and 400 μL samples of the supernatant are added to 10 mL tritium scintillator (6 g butyl PBD, 135 mL toluene, 720 ml dioxan, 100 g naphthalene, 45 mL absolute methanol). Samples are counted for 10 min in a liquid scintillation spectrometer. Counting efficiency is determined by external standardization (35-36 %). Results are represented as a percentage of the specifically bound radioactivity (c.p.m.) in the control tubes^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Mice^[3]
Animals of each sex are divided into two groups: one group receives 4-Hydroxytamoxifen [6 μg/0.1 mL sesame oil/day, subcutaneously (s.c.) starting at 06.00 h] injections for three consecutive days, while the other group receives an equivalent amount of sesame oil injection for 3 days. Four hours following the third injection, each group is then subdivided into two groups: one receives four cumulative doses of methamphetamine hydrochloride (10 mg/kg, s.c.), and the other receives a comparable volume of saline at 2-h intervals. Bilateral gonadectomy is performed under pentobarbital anesthesia (50 mg/kg, intraperitoneally). Five weeks after surgery,gonadectomized mice of each sex are randomly divided into six groups. Five groups of each sex receive three daily injections ofvarious concentrations of 4-Hydroxytamoxifen (0, 1.5, 3.0, 6.0, and 12.0 μg/0.1 mL sesame oil/day). Four hours following the third injection, mice receive four doses of methamphetamine (MA, 10 mg/kg) at 2-h intervals. The remaining group of each sex receives sesame oil pretreatment for three consecutive days, followed by saline injections, and serves as the control group^[3].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Jordan VC, et al. A monohydroxylated metabolite of tamoxifen with potent antioestrogenic activity. J Endocrinol. 1977 Nov;75(2):305-16.

  [2]. Davis KM, et al. Small molecule-triggered Cas9 protein with improved genome-editing specificity. Nat Chem Biol. 2015 May;11(5):316-8.

  [3]. 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.

  [4]. Zhang J, et al. Drug Inducible CRISPR/Cas Systems. Comput Struct Biotechnol J. 2019;17:1171-1177.