曲贝替定
- CAS号:114899-77-3
- 英文名:Trabectedin
- 中文名:曲贝替定
- CBNumber:CB31364731
- 分子式:C39H43N3O11S
- 分子量:761.84
- MOL File:114899-77-3.mol
- 熔点 :>143°C (dec.)
- 比旋光度 :D25 +114° (c = 0.1 in methanol)
- 密度 :1.55±0.1 g/cm3 (20 ºC 760 Torr)
- 储存条件 :-20°C Freezer, Under inert atmosphere
- 溶解度 :Chloroform (Slightly), Methanol (Slightly)
- 酸度系数(pKa) :9.73±0.40(Predicted)
- 形态 :Solid
- 颜色 :Light Yellow to Yellow
- 旋光性 (optical activity) :-53.824.5 (CHCl3)
- InChIKey :PKVRCIRHQMSYJX-HAHYLZASNA-N
曲贝替定性质、用途与生产工艺
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用途
曲贝替定是一种烷化剂药物适用为有不可切除或转移脂肪肉瘤或平滑肌肉瘤患者接受一个以前含蒽环类药物[anthracycline]-方案的治疗。
- 软组织肉瘤治疗新药-曲贝替定 2015年10月23日，美国FDA通过优先审批途径批准了美国强生旗下杨森（Janssen）公司的药物曲贝替定（Trabectedin）上市，商品名为Yondelis。用于不可切除或转移、曾接受过含一种蒽环类药物化疗的脂肪肉瘤和平滑肌肉瘤患者的治疗。曲贝替定为烷化剂属于细胞毒类药，2007年EMEA批准其在欧洲首次上市，用于治疗晚期软组织肉瘤。后又被批准在欧洲和加拿大等地区治疗复发卵巢癌；生产商是西班牙生物技术公司Zeltia和美国强生（Johnson and Johnson）。
- 生物活性 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，从 Ecteinascidia turbinata 中分离出来。 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。
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靶点
IC50: 0.1 nM (MX-1 cells), 1.5 nM (MCF7 cells) and 3.7 nM (MCF7/DXR cells)
Reactive oxygen species (ROS)
Apoptosis -
体外研究
Trabectedin (ET-743; 10 nM; 24-72 hours; MCF7 cells) treatment cells accumulate in late S to G2 phase.
Trabectedin (Ecteinascidin 743) inhibits cell growth of MX-1, MCF7 and MCF7/DXR cells with IC 50 values of 0.1 nM, 1.5 nM and 3.7 nM, respectively.
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.
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.Cell Cycle Analysis
Cell Line: MCF7 cells Concentration: 10 nM Incubation Time: 24 hours, 48 hours, 72 hours Result: Led to pronounced S-G2-M accumulation. -
体内研究
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.
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.Animal Model: Female athymic nude mice bearing the nu/nu gene (5-6 weeks old, 18-20 g) injected with MX-1 cells 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.
- 更新日期：2024/08/19
- 产品编号：HY-50936
- 产品名称：曲贝替定 Trabectedin
- CAS编号：114899-77-3
- 包装：1mg
- 价格：1350元
- 更新日期：2024/08/19
- 产品编号：HY-50936
- 产品名称：曲贝替定 Trabectedin
- CAS编号：114899-77-3
- 包装：5 mg
- 价格：3450元
- 公司名称：PHARMA MAR SA
- 联系电话：--
- 电子邮件：pharmamar@pharmamar.com
- 国家：西班牙
- 产品数：2
- 优势度：58
