| 名稱 | Fulvestrant |
| 描述 | Fulvestrant (ZM 182780) is an estrogen receptor (ER) antagonist (IC50=9.4 nM) and an agonist of GPR30. Fulvestrant has antitumor activity, inhibiting cell proliferation and inducing apoptosis and autophagy. |
| 細(xì)胞實(shí)驗(yàn) | In brief, hippocampi were dissected from the brains of embryonic day 18 Sprague-Dawley rat fetuses, treated with 0.02% trypsin in Hanks' balanced salt solution (137 mM NaCl, 5.4 mM KCl, 0.4 mM KH2PO4, 0.34 mM Na2HPO4·7H2O, 10.0 mM glucose, and 10.0 mM HEPES) at 37°C for 5 min and dissociated by repeated passage through a series of fire-polished constricted Pasteur pipettes. For intracellular Ca2+ imaging analyses, approximately 10^4 cells were seeded onto poly-D-lysine (10 μg/ml)-coated 22-mm coverslips in covered 35-mm Petri dishes. For neuroprotection and Western immunoblotting analyses, approximately 10^6 cells/ml were seeded onto poly-D-lysine-coated solid black and clear bottom 96-well culture plates and 60-mm Petri dishes, respectively. Cells were grown in phenol-red free neurobasal medium supplemented with B27, 5 U/ml penicillin, 5 μg/ml streptomycin, 0.5 mM glutamine, and 25 μM glutamate at 37°C in 10% CO2 for the first 3 days and NBM without glutamate afterward. Cultures grown in serum-free NBM yields approximately 99.5% neurons and 0.5% glial cells [2]. |
| 動(dòng)物實(shí)驗(yàn) | MCF-7 cells were suspended in culture medium (no serum) and inoculated s.c. into the flank of adult female nude mice (0.1 ml/approximately 5 x 10^6 cells). Mice were maintained in a clean environment and were given sterile food and water. Estrogen supplementation was provided by ethynyl estradiol at 1 μg/ml in the water. Antiestrogen treatment was initiated when tumor diameter attained a minimum of 0.5 cm. The Br10 tumor at passage 49 was established by implantation of 1-2-mm^3 tumor fragments into the flank of anesthetized intact adult female nude mice. After 3 passages a reproducible pattern of growth was established without additional estrogen supplementation. Approximately two-thirds of animals established progressively growing tumors which attained measurable size (area, ≥70 mm2) after 6-7 weeks. Antiestrogen treatment was initiated at the time of transplantation. Tamoxifen was administered once daily p.o. at a dose of 10 mg/kg (1 ml/100 g body weight of aqueous dispersion in 0.5% Tween 80) and ICI 182,780 as a single s.c. injection of 5 mg/mouse (50 mg/ml in arachis oil). Tumor size was assessed weekly as the product of caliper measurements of the largest diameter and the axis perpendicular to it [1]. |
| 體外活性 | 方法：ER 陽(yáng)性 MCF-7 和 ER 陰性 MDA-MB-231 細(xì)胞用 Fulvestrant (0.01-10000 nM) 處理 6 天，使用 crystal violet staining 檢測(cè)細(xì)胞生長(zhǎng)速率。
結(jié)果：Fulvestrant 抑制 MCF-7 細(xì)胞的生長(zhǎng)，IC50 為 0.8 nM。Fulvestrant 不抑制 MDA-MB-231 細(xì)胞的生長(zhǎng)，IC50 大于 1 μM。[1]
方法：人乳腺癌細(xì)胞 MCF-7 用 Fulvestrant (100 nM) 處理 0.25-6 h，使用 Western Blot 檢測(cè)靶點(diǎn)蛋白表達(dá)水平。
結(jié)果：當(dāng) MCF-7 細(xì)胞暴露于 Fulvestrant 時(shí)，ERα 蛋白的表達(dá)以時(shí)間依賴的方式減少。[2] |
| 體內(nèi)活性 | 方法：為檢測(cè)體內(nèi)抗腫瘤活性，將 Fulvestrant (25-200 mg/kg，5% DMSO/95% corn oil) 皮下注射給攜帶 tamoxifen-resistant (TamR) 腫瘤的 Nu/J 小鼠，每周四次，持續(xù)四周。
結(jié)果：所有劑量的 Fulvestrant 對(duì)腫瘤生長(zhǎng)的顯著抑制，并且在劑量之間沒(méi)有檢測(cè)到顯著差異。[3]
方法：為檢測(cè)體內(nèi)抗腫瘤活性，將 Fulvestrant (5 mg/mouse) 皮下注射給原位建立 ER+ 乳腺癌的裸鼠，每周兩次，持續(xù)二十四天。
結(jié)果：Fulvestrant 治療導(dǎo)致腫瘤生長(zhǎng)顯著降低。[4] |
| 存儲(chǔ)條件 | keep away from direct sunlight,keep away from moisture,store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | Ethanol : 30.3 mg/mL (50 mM)
DMSO : 45 mg/mL (74.16 mM)
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 6.07 mg/mL (10 mM), Suspension. Please add co-solvents sequentially, clarifying the solution as much as possible before adding the next one. Dissolve by heating and/or sonication if necessary. Working solution is recommended to be prepared and used immediately.
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| 關(guān)鍵字 | Estrogen Receptor/ERR | Inhibitor | Autophagy | ICI-182780 | inhibit | ZM182780 | Fulvestrant | ZD9238 | Apoptosis | ICI182780 | ZM-182780 | ZD-9238 |
| 相關(guān)產(chǎn)品 | Guanidine hydrochloride | Naringin | Valproic Acid | L-Glutamic acid | Gefitinib | Hydroxychloroquine | Dextran sulfate sodium salt (MW 4500-5500) | Stavudine | Tributyrin | L-Ascorbic acid | Paeonol | Sodium 4-phenylbutyrate |
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