Trabectedin (Ecteinascidin 743; ET-743) 是一种四氢异喹啉生物碱,具有有效的抗肿瘤活性。 Trabectedin 与 DNA 的小沟结合,阻断应激诱导的蛋白质的转录,诱导 DNA 骨架裂解和癌细胞凋亡 (apoptosis),并增加 MCF-7 和 MDA-MB-453 细胞中ROS的生成。Trabectedin 可用于软组织肉瘤和卵巢癌的研究。
生物活性 | Trabectedin (Ecteinascidin 743; ET-743) is a tetrahydroisoquinoline alkaloid with potent antitumor activity. Trabectedin binds to the minor groove of DNA, blocks transcription of stress-induced proteins, induces DNA backbone cleavage andcancercellsapoptosis, and increases the generation ofROSin MCF-7 and MDA-MB-453 cells. Trabectedin has the potential for soft tissue sarcoma and ovariancancerresearch[1][2][3]. |
IC50& Target | IC50: 0.1 nM (MX-1 cells), 1.5 nM (MCF7 cells) and 3.7 nM (MCF7/DXR cells)[1] Reactive oxygen species (ROS)[2] Apoptosis[2] |
体外研究 (In Vitro) | Trabectedin (ET-743; 10 nM; 24-72 hours; MCF7 cells) treatment results in cell accumulation in late S to G2 phase[1]. Trabectedin inhibits cell growth of MX-1, MCF7 and MCF7/DXR cells with IC50values of 0.1 nM, 1.5 nM and 3.7 nM, respectively[1]. Trabectedin induces cytotoxicity and apoptosis in both breast cancer cells in a time and concentration-dependent manner. The expression levels of the death receptor pathway molecules, TRAIL-R1/DR4, TRAIL-R2/DR5, FAS/TNFRSF6, TNF RI/TNFRSF1A, and FADD are significantly increased by 2.6-, 3.1-, 1.7-, 11.2- and 4.0-fold by Trabectedin treatment in MCF-7 cells. In MDA-MB-453 cells, the mitochondrial pathway related pro-apoptotic proteins Bax, Bad, Cytochrome c, Smac/DIABLO, and Cleaved Caspase-3 expressions are induced by 4.2-, 3.6-, 4.8-, 4.5-, and 4.4-fold, and the expression levels of anti-apoptotic proteins Bcl-2 and Bcl-XL are reduced by 4.8- and 5.2-fold in MDA-MB-453 cells[2]. In vitro treatment with noncytotoxic concentrations of Trabectedin selectively inhibits the production of CCL2, CXCL8, IL-6, VEGF, and PTX3 by myxoid liposarcoma (MLS) primary tumor cultures and/or cell lines[3].
Cell Cycle Analysis[1] Cell Line: | MCF7 cells | Concentration: | 10 nM | Incubation Time: | 24 hours, 48 hours, 72 hours | Result: | Led to pronounced S-G2-M accumulation. |
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体内研究 (In Vivo) | Trabectedin (ET-743; 30-50 μg/kg; intravenous injection; every three days; female athymic nude mice) treatment increases the antitumor effects in nude mice bearing MX-1 mammary carcinoma xenografts without increasing toxicity[1]. A xenograft mouse model of human myxoid liposarcoma (MLS) shows marked reduction of CCL2, CXCL8, CD68+ infiltrating macrophages, CD31+ tumor vessels, and partial decrease of PTX3 after Trabectedin treatment[3].
Animal Model: | Female athymic nude mice bearing the nu/nu gene (5-6 weeks old, 18-20 g) injected with MX-1 cells[1] | Dosage: | 30 μg/kg, 40 μg/kg, 50 μg/kg | Administration: | Intravenous injection; every three days | Result: | Increased the antitumor effects in nude mice bearing MX-1 mammary carcinoma xenografts without increasing toxicity. |
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结构分类 | - Alkaloids
- Isoquinoline Alkaloids
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运输条件 | Room temperature in continental US; may vary elsewhere. |
储存方式 | -20°C, protect from light, stored under nitrogen *该产品在溶液状态不稳定,建议您现用现配,即刻使用。 |
溶解性数据 | In Vitro: DMSO : 33.33 mg/mL(43.75 mM;Need ultrasonic) 配制储备液 1 mM | 1.3126 mL | 6.5631 mL | 13.1261 mL | 5 mM | 0.2625 mL | 1.3126 mL | 2.6252 mL | 10 mM | 0.1313 mL | 0.6563 mL | 1.3126 mL |
*请根据产品在不同溶剂中的溶解度,选择合适的溶剂配制储备液;该产品在溶液状态不稳定,建议您现用现配,即刻使用。 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;
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此方案可获得 ≥ 2.5 mg/mL (3.28 mM,饱和度未知) 的澄清溶液。 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 μL20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。 2. 请依序添加每种溶剂: 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (3.28 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (3.28 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。 3. 请依序添加每种溶剂: 5% DMSO 40%PEG300 5%Tween-80 50% saline Solubility: ≥ 2.5 mg/mL (3.28 mM); Clear solution
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