| 规格 | 价格 | 库存 | 数量 |
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| 靶点 |
ER
AKT Protein (Serine/Threonine Kinase): Estradiol Cypionate regulates AKT ubiquitination to inhibit its activity [4] |
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| 体外研究 (In Vitro) |
当暴露于环丙酸雌二醇 (0-30 μM) 72 小时时，胃癌细胞（MGC803、SGC7901 和 BGC823）无法增殖 [4]。在胃癌细胞（MGC803、SGC7901 和 BGC823 细胞）的 G1/S 期，环戊丙酸雌二醇 (10–25 μM) 可通过 PI3K/Akt/mTOR 途径引起细胞周期停滞并引发细胞凋亡 [4]。
胃癌细胞的抗肿瘤活性（[4]）： 用环戊丙酸雌二醇（1–50 μM）处理MGC-803和SGC-7901（人胃癌）细胞48小时，呈浓度依赖抑制增殖，MTT实验显示IC50值分别为8.5 μM（MGC-803）和10.2 μM（SGC-7901）。20 μM时显著促进凋亡：Annexin V阳性细胞比例较对照增加45%（MGC-803）和40%（SGC-7901）（流式细胞术）。蛋白质印迹法显示：（1）p-AKT（Ser473）蛋白水平在MGC-803中降低60%，SGC-7901中降低55%；（2）切割型caspase-3和切割型PARP在MGC-803中分别上调3.2倍和2.8倍；（3）AKT泛素化水平上调2.5倍（免疫沉淀+蛋白质印迹法）。浓度达20 μM时，对正常人胃上皮细胞（GES-1）无显著细胞毒性（活力较对照>90%）[4] |
| 体内研究 (In Vivo) |
在青春期卵巢切除 (OVX) 兔子中，每周肌内注射环戊丙酸雌二醇 (70 μg/kg) 可增加皮质骨密度 [2]。在奶牛中，肌肉注射1mg环戊丙酸雌二醇会增加发情和妊娠的发生率[3]。环丙酸雌二醇（50-100mg/kg，腹腔注射，每隔一天）抑制MGC803裸鼠肿瘤生长[4]。
胃癌异种移植模型的抗肿瘤疗效（[4]）： 6–8周龄雌性BALB/c裸鼠皮下接种5×10⁶ MGC-803细胞，肿瘤体积达100 mm³后，随机分为对照组（溶剂）和环戊丙酸雌二醇组（5 mg/kg/天，腹腔注射）。治疗21天后：（1）环戊丙酸雌二醇组肿瘤体积较对照减少58%（肿瘤体积=长×宽²/2，每周测量两次）；（2）肿瘤重量减少52%（0.48±0.06 g vs 对照1.00±0.12 g）；（3）肿瘤组织免疫组化显示：p-AKT阳性率降低55%，切割型caspase-3阳性率增加60%。环戊丙酸雌二醇组小鼠体重、肝功能（ALT、AST）及肾功能（BUN、肌酐）均无显著变化 [4] |
| 酶活实验 |
环戊丙酸雌二醇（Depoestradiol；Estradiol cypionate; β-雌二醇 17-环戊丙酸酯）通过调节AKT泛素化抑制癌症增殖和促进细胞凋亡：癌症是世界范围内常见的胃肠道恶性肿瘤，死亡率高，预后差。多药耐药性仍然是患者成功治疗的主要障碍。因此，开发新的疗法来增强抗肿瘤作用具有重要意义。在本研究中，我们在体外和体内研究了Estradiol cypionate（ECP）对癌症的影响。我们的数据表明，ECP抑制癌症细胞的增殖，促进细胞凋亡，并导致G1/S期阻滞。ECP促进癌症细胞凋亡的机制与AKT泛素化修饰水平升高引起的AKT蛋白表达下调有关，最终抑制PI3K-AKT-mTOR信号通路的过度激活。体内肿瘤发生实验表明，ECP能显著抑制癌症细胞的生长，具有临床应用前景。上述结果表明，ECP通过PI3K/Akt/mTOR途径抑制癌症的生长并诱导细胞凋亡。总之，我们数据中显示的疗效表明，ECP是一种治疗癌症的有前途的抗肿瘤化合物[4]。
AKT泛素化检测实验（[4]）： 1. 细胞制备：MGC-803细胞接种于10 cm培养皿（5×10⁶细胞/皿），培养至70%汇合度。 2. 药物处理：用环戊丙酸雌二醇（20 μM）处理细胞24小时；对照组加入0.1% DMSO。 3. 免疫沉淀：细胞用含蛋白酶和磷酸酶抑制剂的RIPA缓冲液裂解；取500 μg细胞裂解液与1 μg抗AKT抗体在4°C孵育过夜，再加入蛋白A/G琼脂糖珠在4°C孵育4小时。 4. 蛋白质印迹检测：琼脂糖珠用裂解液洗涤3次；沉淀蛋白经SDS-PAGE分离后转移至PVDF膜，用抗泛素抗体和抗AKT抗体孵育；条带强度用ImageJ软件定量 [4] |
| 细胞实验 |
蛋白质印迹分析[4]
细胞类型： MGC803、SGC7901 和 BGC823 细胞 测试浓度： 10-25 μM 孵育持续时间： 48 小时 实验结果： 裂解 caspase-3 和 PARP 的蛋白质水平增加。 AKT、p-AKT、p-mTOR、p-S6K 和 p-4E-BP1 的蛋白质水平降低。 胃癌细胞实验（[4]）： 1. 细胞培养：MGC-803/SGC-7901（胃癌细胞）和GES-1（正常胃上皮细胞）用含10%胎牛血清的RPMI 1640培养基培养，置于37°C、5% CO₂孵箱中。 2. 细胞接种： - 增殖实验：接种于96孔板（5×10³细胞/孔）； - 凋亡实验：接种于6孔板（2×10⁵细胞/孔）； - 蛋白检测：接种于10 cm培养皿（5×10⁶细胞/皿）。 3. 药物处理：贴壁24小时后，用环戊丙酸雌二醇（1–50 μM）处理48小时（增殖/凋亡实验）或24小时（蛋白检测）；对照组加入0.1% DMSO。 4. 检测方法： - 增殖：加入MTT试剂，在570 nm处测定吸光度，计算IC50； - 凋亡：细胞用Annexin V-FITC/PI染色，流式细胞术分析； - 蛋白表达：蛋白质印迹法检测p-AKT（Ser473）、AKT、切割型caspase-3、切割型PARP（以β-肌动蛋白为内参）[4] |
| 动物实验 |
Animal/Disease Models: MGC803 nude mice tumor model[4].
Doses: 50-100 mg/kg Route of Administration: ip, every other day Experimental Results: Inhibited tumor growth. Increased Cleaved caspase-3 expression, diminished Ki67, AKT and p-AKT in tumors . Gastric Cancer Xenograft Protocol ([4]): 1. Animal Selection: 6–8 weeks old female BALB/c nude mice (n=6/group) randomized to control and Estradiol Cypionate groups. 2. Tumor Model Establishment: 5×10⁶ MGC-803 cells were suspended in 0.2 mL PBS containing 50% Matrigel, then subcutaneously injected into the right flank of nude mice. 3. Drug Preparation: Estradiol Cypionate was dissolved in DMSO (5% v/v) and diluted with normal saline (95% v/v) to a concentration of 0.5 mg/mL. 4. Administration: When tumor volume reached 100 mm³, the Estradiol Cypionate group received intraperitoneal injection (10 mL/kg body weight, 5 mg/kg/day) once daily for 21 days; the control group received the same volume of vehicle (5% DMSO + 95% normal saline). 5. Sample Collection & Detection: - Tumor Measurement: Tumor length and width measured twice weekly to calculate volume; - Euthanasia & Sampling: Mice euthanized after 21 days; tumor tissues weighed and fixed in 4% paraformaldehyde for immunohistochemistry (p-AKT, cleaved caspase-3); serum collected to detect liver/kidney function indices [4] |
| 药代性质 (ADME/PK) |
Absorption, Distribution and Excretion
When conjugated with aryl and alkyl groups for parenteral administration, the rate of absorption of oily preparations is slowed with a prolonged duration of action, such that a single intramuscular injection of estradiol valerate or estradiol cypionate is absorbed over several weeks. Estradiol, estrone and estriol are excreted in the urine along with glucuronide and sulfate conjugates. The distribution of exogenous estrogens is similar to that of endogenous estrogens. Estrogens are widely distributed in the body and are generally found in higher concentrations in the sex hormone target organs. Metabolism / Metabolites Exogenous estrogens are metabolized in the same manner as endogenous estrogens. Circulating estrogens exist in a dynamic equilibrium of metabolic interconversions. These transformations take place mainly in the liver. Estradiol is converted reversibly to estrone, and both can be converted to estriol, which is the major urinary metabolite. Estrogens also undergo enterohepatic recirculation via sulfate and glucuronide conjugation in the liver, biliary secretion of conjugates into the intestine, and hydrolysis in the gut followed by reabsorption. In postmenopausal women, a significant proportion of the circulating estrogens exist as sulfate conjugates, especially estrone sulfate, which serves as a circulating reservoir for the formation of more active estrogens. |
| 毒性/毒理 (Toxicokinetics/TK) |
Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation Estradiol cypionate has not been studied during breastfeeding. However, a similar drug, estradiol valerate, has been used to suppress lactation, usually in combination with testosterone. Generally, estradiol cypionate should be avoided in mothers wishing to breastfeed, especially if started before the milk supply is well established at about 6 weeks postpartum. The decrease in milk supply can happen over the first few days of estrogen exposure. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Another injection ester form of estradiol, estradiol valerate was previously used therapeutically to suppress lactation, usually in combination with testosterone. A retrospective cohort study compared 371 women who received high-dose estrogen (either 3 mg of diethylstilbestrol or 150 mcg of ethinyl estradiol daily) during adolescence for adult height reduction to 409 women who did not receive estrogen. No difference in breastfeeding duration was found between the two groups, indicating that high-dose estrogen during adolescence has no effect on later breastfeeding. Protein Binding Estrogens circulate in the blood largely bound to sex hormone binding globulin (SHBG) and albumin. 1. In Vitro Toxicity ([4]): Estradiol Cypionate (1–20 μM) showed no significant cytotoxicity to normal human gastric epithelial cells (GES-1), with cell viability >90% vs. control (MTT assay) [4] 2. In Vivo Toxicity ([4]): Mice treated with Estradiol Cypionate (5 mg/kg/day, intraperitoneal injection) for 21 days showed: (1) No significant change in body weight (initial weight 18–20 g, final weight 20–22 g, similar to control); (2) Normal serum levels of ALT (25–35 U/L), AST (40–50 U/L), BUN (5–7 mmol/L), and creatinine (30–40 μmol/L), consistent with control group [4] |
| 参考文献 |
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| 其他信息 |
Pharmacodynamics
Estrogen mediates its effects across the body through potent agonism of the Estrogen Receptor (ER), which is located in various tissues including in the breasts, uterus, ovaries, skin, prostate, bone, fat, and brain. Estradiol binds to both subtypes of the Estrogen Receptor: Estrogen Receptor Alpha (ERα) and Estrogen Receptor Beta (ERβ). Estradiol also acts as a potent agonist of G Protein-coupled Estrogen Receptor (GPER), which has recently been recognized as a major mediator of estradiol's rapid cellular effects. 1. Drug Background ([4]): Estradiol Cypionate is a synthetic, long-acting estrogen ester. It is a prodrug that is hydrolyzed to estradiol (active form) in vivo, but in gastric cancer cells, it directly exerts antitumor effects by regulating AKT ubiquitination (independent of classical estrogen receptor signaling) [4] 2. Mechanism of Action ([4]): Estradiol Cypionate promotes AKT ubiquitination and degradation, thereby reducing the phosphorylation level of AKT (p-AKT). Inhibition of AKT signaling downregulates prosurvival pathways and upregulates the caspase-dependent apoptotic pathway, ultimately inhibiting gastric cancer cell proliferation and inducing apoptosis [4] 3. Therapeutic Potential ([4]): Estradiol Cypionate shows potential as a novel therapeutic agent for gastric cancer, especially for tumors with activated AKT signaling. It has low toxicity to normal gastric epithelial cells, suggesting a favorable safety profile [4] |
| 分子式 |
C26H36O3
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| 分子量 |
396.56
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| 精确质量 |
396.266
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| 元素分析 |
C, 78.75; H, 9.15; O, 12.10
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| CAS号 |
313-06-4
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| 相关CAS号 |
Estradiol;50-28-2;Estradiol benzoate;50-50-0;Estradiol enanthate;4956-37-0; Alpha-Estradiol;57-91-0;Estradiol (Standard);50-28-2;Estradiol-d3;79037-37-9;Estradiol-d4;66789-03-5;Estradiol-d5;221093-45-4;Estradiol-13C2;82938-05-4;Estradiol (cypionate);313-06-4;Estradiol benzoate;50-50-0;Estradiol enanthate;4956-37-0;Estradiol hemihydrate;35380-71-3;Estradiol-d2;53866-33-4;Estradiol-13C6;Estradiol-d2-1;3188-46-3;rel-Estradiol-13C6; 979-32-8 (valerate); 113-38-2 (dipropionate); 57-63-6 (ethinyl); 172377-52-5 (sulfamate); 3571-53-7 (undecylate)
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| PubChem CID |
9403
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| 外观&性状 |
White to off-white solid powder
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| 密度 |
1.2±0.1 g/cm3
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| 沸点 |
532.8±50.0 °C at 760 mmHg
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| 熔点 |
≥300 °C(lit.)
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| 闪点 |
207.7±22.9 °C
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| 蒸汽压 |
0.0±1.5 mmHg at 25°C
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| 折射率 |
1.579
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| LogP |
7.59
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| tPSA |
46.53
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| 氢键供体(HBD)数目 |
1
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| 氢键受体(HBA)数目 |
3
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| 可旋转键数目(RBC) |
5
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| 重原子数目 |
29
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| 分子复杂度/Complexity |
597
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| 定义原子立体中心数目 |
5
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| SMILES |
C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@@H]2OC(=O)CCC4CCCC4)CCC5=C3C=CC(=C5)O
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| InChi Key |
UOACKFBJUYNSLK-XRKIENNPSA-N
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| InChi Code |
InChI=1S/C26H36O3/c1-26-15-14-21-20-10-8-19(27)16-18(20)7-9-22(21)23(26)11-12-24(26)29-25(28)13-6-17-4-2-3-5-17/h8,10,16-17,21-24,27H,2-7,9,11-15H2,1H3/t21-,22-,23+,24+,26+/m1/s1
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| 化学名 |
Cyclopentanepropionic acid, 3-hydroxyestra-1,3,5(10)-trien-17beta-yl ester
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| 别名 |
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| HS Tariff Code |
2934.99.9001
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| 存储方式 |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month 注意： (1). 本产品在运输和储存过程中需避光。 (2). 请将本产品存放在密封且受保护的环境中（例如氮气保护），避免吸湿/受潮。 |
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| 运输条件 |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| 溶解度 (体外实验) |
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| 溶解度 (体内实验) |
配方 1 中的溶解度: ≥ 2.67 mg/mL (6.73 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 26.7 mg/mL的澄清DMSO储备液加入到400 μL PEG300中并混合均匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。 *生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。 配方 2 中的溶解度: ≥ 2.67 mg/mL (6.73 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。 例如，若需制备1 mL的工作液，可将 100 μL 26.7 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。 请根据您的实验动物和给药方式选择适当的溶解配方/方案： 1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液)); 2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方): 10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline); 假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL； 3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例; 4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶; 5、为保证最佳实验结果，工作液请现配现用！ 6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们; 7、 以上所有助溶剂都可在 Invivochem.cn网站购买。 |
| 制备储备液 | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5217 mL | 12.6084 mL | 25.2169 mL | |
| 5 mM | 0.5043 mL | 2.5217 mL | 5.0434 mL | |
| 10 mM | 0.2522 mL | 1.2608 mL | 2.5217 mL |
1、根据实验需要选择合适的溶剂配制储备液 (母液)：对于大多数产品，InvivoChem推荐用DMSO配置母液 (比如：5、10、20mM或者10、20、50 mg/mL浓度），个别水溶性高的产品可直接溶于水。产品在DMSO 、水或其他溶剂中的具体溶解度详见上”溶解度 (体外)”部分;
2、如果您找不到您想要的溶解度信息，或者很难将产品溶解在溶液中，请联系我们;
3、建议使用下列计算器进行相关计算（摩尔浓度计算器、稀释计算器、分子量计算器、重组计算器等）;
4、母液配好之后，将其分装到常规用量，并储存在-20°C或-80°C，尽量减少反复冻融循环。
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)。如该浓度超过该批次药物DMSO溶解度，请首先与我们联系。
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 ddH2O，混匀澄清。
(1) 请确保溶液澄清之后，再加入下一种溶剂 (助溶剂) 。可利用涡旋、超声或水浴加热等方法助溶；
(2) 一定要按顺序加入溶剂 (助溶剂) 。
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