Zibotentan (ZD4054) 是一种有效的，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。Zibotentan 对 ETB 没有抑制作用。Zibotentan 具有抗癌作用，可用于去势抵抗性前列腺癌 (CRPC) 的研究。
| 生物活性 | Zibotentan (ZD4054) is a potent, selective and orally activeendothelin A (ETA) receptorantagonist with aKiof 13 nM. Zibotentan has no inhibitory effect on ETB. Zibotentan has anticancer effects and can be used for castration-resistant prostatecancer(CRPC) research[1][2]. |
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体外研究
(In Vitro) | Zibotentan potently inhibits the binding of125iodine-ET-1 to cloned human ETA expressed in mouse erythroleukaemic cells, with a pIC50(concentration to inhibit 50% of binding) value of 22 nM[1].
Zibotentan (48 hours) treatment increases the number of early apoptotic cells in serum-starved A2780 WT cells[2].
Zibotentan (ZD4054; 1 μM; 24 hours) treatment shows significant inhibition of cell proliferation in serum-starved HEY, OVCA 433, SKOV-3, and A-2780 cells[3].
Zibotentan (ZD4054; 1 μM; 48 hours) treatment induces an increase in apoptotic cells. Zibotentan inhibits bcl-2 and activates caspase-3 and poly(ADP-ribose) polymerase proteins.[3].
Zibotentan (ZD4054; 1 μM) decreases the endogenous ET-1-induced phosphorylation/activation of both kinases (AKT and p42/44MAPK) in HEY cells[3].
Zibotentan treatment also results in a reduction of ETAR-driven angiogenesis and invasive mediators, such as vascular endothelial growth factor, cyclooxygenase-1/2, and matrix metalloproteinase (MMP)[3].
Cell Proliferation Assay[3] | Cell Line: | HEY, OVCA 433, SKOV-3, and A-2780 cells | | Concentration: | 1 μM | | Incubation Time: | 24 hours | | Result: | Showed significant inhibition of cell proliferation. |
Apoptosis Analysis[3] | Cell Line: | HEY and OVCA 433 cells | | Concentration: | 1 μM | | Incubation Time: | 48 hours | | Result: | Induced an increase in apoptotic cells. |
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体内研究
(In Vivo) | Zibotentan (10 mg/kg; intraperitoneal injection; daily; for 21 days) treatment significantly inhibits tumor growth in mice. And Zibotentan treatment increases E-cadherin expression[2].
| Animal Model: | Female athymic (nu+/nu+) mice (4-6 week of age) injected with wild-type A2780 cells[2] | | Dosage: | 10 mg/kg | | Administration: | Intraperitoneal injection; daily ; for 21 days | | Result: | Showed significant inhibition in tumor growth in mice. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 25 mg/mL(58.90 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.3561 mL | 11.7805 mL | 23.5610 mL | | 5 mM | 0.4712 mL | 2.3561 mL | 4.7122 mL | | 10 mM | 0.2356 mL | 1.1781 mL | 2.3561 mL |
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储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 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 90%corn oil Solubility: ≥ 2.5 mg/mL (5.89 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (5.89 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 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。
*以上所有助溶剂都可在本网站选购。 |
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