Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Zibotentan (ZD4054) 是一种选择性的,具有口服活性的内皮素 A (ETA) 受体拮抗剂,Ki 为 13 nM。它具有抗癌作用,可研究去势抵抗性前列腺癌。
规格 | 价格/CNY | 货期 | 数量 | |
---|---|---|---|---|
1 mg | ¥ 385 | 现货 | ||
2 mg | ¥ 549 | 现货 | ||
5 mg | ¥ 872 | 现货 | ||
10 mg | ¥ 1,490 | 现货 | ||
25 mg | ¥ 2,530 | 现货 | ||
50 mg | 特惠询价 | 现货 | ||
1 mL * 10 mM (in DMSO) | ¥ 959 | 现货 |
产品描述 | Zibotentan (ZD4054) (ZD4054) is a specific Endothelin (ET)A antagonist with IC50 of 21 nM, exhibiting no activity at ETB. Phase 3. |
靶点活性 | ET-A:21 nM |
体外活性 | As Zibotentan specifically inhibits ETA-mediated antiapoptotic effects, but not ETB-mediated proapoptotic effects in human and rat smooth muscle cells, Zibotentan binds to endothelin A receptor (ETA) with high affinity with Ki of 13 nM, and has no affinity for endothelin B receptor (ETB) with IC50 of >10 μM. [1] Zibotentan treatment at 1 μM inhibits ET-1 induced mitogenic activity in ovarian carcinoma cell lines HEY and OVCA 433 secreting ET-1 and expressing ETA and ETB mRNA. [2] ZD4054 (1 μM) inhibits ET-1 induced EGFR transactivation in HEY and OVCA 433 cells. Zibotentan (1 μM) reverts ET-1 mediated epithelial-mesenchymal transition (EMT), by enhancing E-cadherin expression and promoter activity, and inhibiting vascular endothelial growth factor (VEGF) secretion and invasiveness in HEY and OVCA 433 cells. [3] Zibotentan also potently inhibits the basal and ET-1 induced cell proliferation in SKOV-3 and A-2780 cells, associated with the inhibition of AKT and p42/44MAPK phosphorylation, and with increased apoptosis through the inhibition of bcl-2 and activation of caspase-3 and poly(ADP-ribose) polymerase proteins. [4] |
体内活性 | Administration of Zibotentan at 10 mg/kg/day for 21 days potently inhibits the growth of HEY ovarian carcinoma xenografts in mice by 69% with no associated toxicity, which is in association with the blocking of cell proliferation evaluated by 37% inhibition of the Ki-67 expression, and the 62% inhibition of tumor-induced vascularization. Consistently, Zibotentan treatment significantly inhibits the expression of matrix metalloproteinase-2 (MMP-2) and VEGF, as well as the activation of p42/44 MAPK and EGFR, and potently enhances the expression of E-cadherin. [3] |
激酶实验 | Receptor-binding assays: The inhibition by Zibotentan (varying concentrations) of 125iodine-ET-1 binding to cloned human ETA is assessed using standard radioligand-binding techniques. Human recombinant ETA is expressed in mouse erythroleukaemic cells, and cell membranes prepared for competitive binding studies using 125iodine-ET-1 as the radioligand. Incubations are carried out in triplicate in the presence of Zibotentan, 100 pM to 100 μM in half-log increments, and inhibition of ET-1 binding is expressed as the geometric mean pIC50 value (concentration to inhibit 50% of binding) with a 95% confidence interval (CI). The affinity of Zibotentan for cloned human ETA is also assessed using the equation of Cheng and Prusoff to determine the equilibrium dissociation constant (Ki) in a further receptor-binding screen utilizing a greater number of concentration-response curves determined in three separate studies. |
细胞实验 | Cells are serum starved by incubation for 24 hours in serum-free DMEM before exposed to Zibotentan for 48 hours. After the treatment, cells are lysed and the supernatant is recovered and assayed for histone-associated DNA fragments, at 405 nm by the use of a microplate reader. For detection of early apoptotic events, floating and adherent cells are collected. Cells are double stained with FITC-conjugated Annexin V and propidium iodide using the Vybrant Apoptosis Kit and are immediately analyzed by cytofluorometric analysis.(Only for Reference) |
别名 | ZD4054 |
分子量 | 424.43 |
分子式 | C19H16N6O4S |
CAS No. | 186497-07-4 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
DMSO: 23 mg/mL (54.2 mM)
Ethanol: < 1 mg/mL (insoluble or slightly soluble)
H2O: < 1 mg/mL (insoluble or slightly soluble)
可选溶剂 | 浓度 体积 质量 | 1 mg | 5 mg | 10 mg | 25 mg |
DMSO | 1 mM | 2.3561 mL | 11.7805 mL | 23.561 mL | 58.9025 mL |
5 mM | 0.4712 mL | 2.3561 mL | 4.7122 mL | 11.7805 mL | |
10 mM | 0.2356 mL | 1.1781 mL | 2.3561 mL | 5.8903 mL | |
20 mM | 0.1178 mL | 0.589 mL | 1.1781 mL | 2.9451 mL | |
50 mM | 0.0471 mL | 0.2356 mL | 0.4712 mL | 1.1781 mL |
对于不同动物的给药剂量换算,您也可以参考 更多...
请在以下方框中输入您的动物实验信息后点击计算,可以得到母液配置方法和体内配方的制备方法: 比如您的给药剂量是10 mg/kg,每只动物体重20 g,给药体积100 μL,一共给药动物10 只,您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。
母液配置方法:2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL), 如您需要配置的浓度超过该产品的溶解度,请先与我们联系。
体内配方的制备方法:取 50 μL DMSO 主液,加入 300 μL PEG300, 混匀澄清,再加 50 μL Tween 80,混匀澄清,再加 600 μL ddH2O, 混匀澄清。
您可能有的问题的答案可以在抑制剂处理说明中找到,包括如何准备库存溶液,如何存储产品,以及基于细胞的分析和动物实验需要特别注意的问题。
Zibotentan 186497-07-4 Apoptosis GPCR/G Protein Endothelin Receptor 44MAPK ETA Inhibitor bcl-2 ZD-4054 ZD 4054 CRPC ZD4054 inhibit p42 anticancer caspase-3 inhibitor