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Raltitrexed

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Chemical Structure| 112887-68-0 同义名 : ZD1694;D1694;brand name: Tomudex.;TDX;ICI-D1694
CAS号 : 112887-68-0
货号 : A222261
分子式 : C21H22N4O6S
纯度 : 98%
分子量 : 458.488
MDL号 : MFCD00864168
存储条件：

粉末 Keep in dark place,Inert atmosphere,Room temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 30 mg/mL(65.43 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 2% DMSO+2% Tween80+30% PEG300+water 8 mg/mL clear

PO 0.5% CMC-Na 42 mg/mL suspension

生物活性
描述 Thymidylate synthase (TS) is critical enzyme for the synthesis of DNA- it converts dUMP (2′-deoxyuridine-5′-monophosphate) into dTMP (2′-deoxythymidine-5′-monophosphate). Raltitrexed is an antimetabolite drug used in chemotherapy, and was developed as a direct and specific inhibitor of TS[3]. Raltitrexed (0.5 μg/mL) shows typical apoptotic morphology, including nuclear shrinkage, fragmentation, chromatin condensation and apoptotic bodies in SGC7901 cells. Raltitrexed blocks the cell cycle at the G0/G1 phase, decreases in the mitochondrial membrane potential. Raltitrexed also increases the level of ROS, induces caspase-3-dependent apoptosis via activation of the mitochondria, and increases TS protein and mRNA expression levels[4]. Raltitrexed (1.5 nM) reduces the number of GM00637 cells, selectively induces gene conversions, but does not affect DSB-induced HR or NHEJ[5]. Raltitrexed (0, 5, 10, 11.5, 13.5, 15 mg/kg b/w, i.p.) increases the rates of resorbed embryos and growth retardation of murine model of NTDs in a dose dependent manner. Raltitrexed (11.5 mg/kg b/w) maximally inhibits the thymidylate synthase (TS) activity in embryonic tissue, decreases dTMP levels and while increases dUMP levels[6].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
chinese hamster D4 cells Proliferation assay 96 h Antiproliferative activity against chinese hamster D4 cells expressing human FRbeta assessed as reduction of viable cells after 96 hrs, IC50=22 nM 21879757
human HepG2 cells Cytotoxicity assay 48 h Cytotoxicity against human HepG2 cells after 48 hrs by MTT assay, IC50=1.3 μM 23490159
human IGROV1 cells Proliferation assay Antiproliferative activity against human RFC and FRalpha expressing human IGROV1 cells, IC50=12.6 nM 18680275
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT02678806 HepatoCellular Carcinoma Not Applicable Recruiting November 1, 2022 China, Guangxi ... 展开 >> TaoBai Recruiting Nanning, Guangxi, China, 530000 Contact: Bai Tao, MD    +86 13878862632    25859373@qq.com 收起 <<
NCT01703910 Adenocarcinoma of Colon ... 展开 >> Adenocarcinoma of Rectum Metastatic Disease 收起 << Phase 2 Completed - Spain ... 展开 >> Hospital Universitario de Fuenlabrada Fuenlabrada, Madrid, Spain, 28950 Hospital Madrid Norte Sanchinarro Madrid, Spain, 28050 收起 <<
NCT01481545 Rectal Cancer Phase 2 Unknown July 2018 -
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.18mL

0.44mL

0.22mL

10.91mL

2.18mL

1.09mL

21.81mL

4.36mL

2.18mL
参考文献

[1]Van Cutsem E, Cunningham D, et al. Raltitrexed: current clinical status and future directions. Ann Oncol. 2002 Apr;13(4):513-22.

[2]Peters GJ, van Triest B, et al. Molecular downstream events and induction of thymidylate synthase in mutant and wild-type p53 colon cancer cell lines after treatment with 5-fluorouracil and the thymidylate synthase inhibitor raltitrexed. Eur J Cancer. 2000 May;36(7):916-24.

[3]Wilson KS, Malfair Taylor SC. Raltitrexed: optimism and reality. Expert Opin Drug Metab Toxicol. 2009;5(11):1447-1454.

[4]Xue S, Chen YX, Qin SK, et al. Raltitrexed induces mitochondrial‑mediated apoptosis in SGC7901 human gastric cancer cells. Mol Med Rep. 2014;10(4):1927-1934.

[5]Waldman BC, Wang Y, Kilaru K, et al. Induction of intrachromosomal homologous recombination in human cells by raltitrexed, an inhibitor of thymidylate synthase. DNA Repair (Amst). 2008;7(10):1624-1635.

[6]Dong Y, Wang X, Zhang J, et al. Raltitrexed's effect on the development of neural tube defects in mice is associated with DNA damage, apoptosis, and proliferation. Mol Cell Biochem. 2015;398(1-2):223-231.