| 名稱 | 4-Hydroxytamoxifen |
| 描述 | 4-Hydroxytamoxifen (ICI 79280) is the active metabolite of Tamoxifen, an estrogen receptor modulator (SERM) with selective and oral potency. 4-Hydroxytamoxifen has antitumor activity and may be used in breast cancer research. |
| 激酶實驗 | 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 is 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 dioxane, 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]. |
| 動物實驗 | 4-Hydroxytamoxifen is formulated in sesame oil[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 of various 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]. |
| 體外活性 | 方法：人子宮內(nèi)膜腺癌細(xì)胞系 HEC-1B 用 4-Hydroxytamoxifen (0.01-100 μM) 處理 3 天，使用 CellTiter 96 AQueous One Solution Cell Proliferation Assay 檢測細(xì)胞活力。
結(jié)果：暴露于更高濃度 (1-100 μM) 的 4-Hydroxytamoxifen 的 HEC-1B 細(xì)胞顯示出不同濃度之間細(xì)胞存活率的顯著差異。[1]
方法：ER-陽性乳腺癌癥細(xì)胞系 MCF-7、T47D 和 BT-474 用 4-Hydroxytamoxifen (0.5-1 μM) 和 sulforaphane (5 μM) 處理 48 h，使用 Western Blot 檢測靶點蛋白表達(dá)水平。
結(jié)果：Sulforaphane 誘導(dǎo) PARP 切割，其強度取決于細(xì)胞系。sulforaphane 和 4-Hydroxytamoxifen 的聯(lián)合治療進(jìn)一步提高了 PARP 的切割。[2] |
| 體內(nèi)活性 | 方法：為檢測體內(nèi)抗腫瘤活性，將 Cholesterol (1 mg/kg) 腹腔注射給攜帶人乳腺癌腫瘤 MCF-7 的 Nu/Nu 小鼠，每天一次，持續(xù)二十三天。
結(jié)果：4-Hydroxytamoxifen 有效地抑制小鼠的腫瘤生長。[3]
方法：為誘導(dǎo) Cre 重組酶活性，將 Cholesterol (30-60 mg/kg) 腹腔注射給 Rosa26BEST1-CreERT2 小鼠，每天一次，持續(xù)四天。
結(jié)果：TdTomato 在兩性小鼠的 RPE 中強烈表達(dá)。[4] |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | H2O : < 0.1 mg/mL (insoluble)
DMSO : 45 mg/mL (116.13 mM)
|
| 關(guān)鍵字 | inhibit | Estrogen Receptor/ERR | 4-hydroxy Tamoxifen | estrogen receptor | oral | CRISPR/Cas9 | ICI79280 | 4-Hydroxytamoxifen | 4Hydroxytamoxifen | Inhibitor | (Z)-Afimoxifene | nucleus translocation | 4 Hydroxytamoxifen | ICI-79280 |
| 相關(guān)產(chǎn)品 | Astragaloside IV | Estradiol | Melatonin | Mifepristone | Ethisterone | Kaempferol | Cholesterol |
| 相關(guān)庫 | 抗癌活性化合物庫 | 經(jīng)典已知活性庫 | 抗癌化合物庫 | 已知活性化合物庫 | ReFRAME 相關(guān)化合物庫 | 內(nèi)分泌激素分子庫 | 抗卵巢癌化合物庫 | NO PAINS 化合物庫 | 口服活性化合物庫 | 人代謝物化合物庫 |