雷替曲塞作用机制 - Medchemexpress - MCE中国

1、Product Data SheetRaltitrexedCat. No.: HY-10821CAS No.: 112887-68-0分式: CHNOS分量: 458.49作靶点: Thymidylate Synthase; Nucleoside Antimetabolite/Analog作通路: Apoptosis; Cell Cycle/DNA Damage储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 29 mg/mL (63.25 mM)* means solu

2、ble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制备储备液1 mM 2.1811 mL 10.9054 mL 21.8107 mL5 mM 0.4362 mL 2.1811 mL 4.3621 mL10 mM 0.2181 mL 1.0905 mL 2.1811 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；旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 储存时，请在 6 个内使，-20C 储存时，请

3、在 1 个内使。体内实验请根据您的实验动物和给药式选择适当的溶解案。以下溶解案都请先按照 In Vitro 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 的储备液可以根据储存条件，适当保存；体内实验的作液，建议您现现配，当天使； 以下溶剂前显的百分 指该溶剂在您配制终溶液中的体积占；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的式助溶1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.45 mM); Clear solution此案可获得 2.5 mg/

4、mL (5.45 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 400 L PEG300 中，混合均匀；向上述体系中加50 L Tween-80，混合均匀；然后继续加 450 L 理盐定容 1 mL。2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.45 mM); Clear solutionPage 1 of 2 www.MedChemE此案可获得 2.5 mg/mL (5.45 mM，饱和度未知) 的澄清溶液。以 1

5、mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 900 L 20% 的 SBE-CD 理盐溶液中，混合均匀。3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (5.45 mM); Clear solution此案可获得 2.5 mg/mL (5.45 mM，饱和度未知) 的澄 溶液，此案不适于实验周 期在半个以上的实验。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 900 L 油中，混合均匀。BIOLOGICAL ACTIVITY物活性 Raltitre

6、xed种于化疗的抗代谢药物，通过抑制胸苷酸合成酶起作。体外研究 Raltitrexed inhibits HepG2 proliferation by arresting the cell cycle at G0/G1, and the cell cycle is mediated viadownregulation of cyclin A and CDK21. Raltitrexed (0.1, 0.5, 2.5 g/mL) decreases the viability of SGC7901 cells in adose- and time-dependent manner. Raltit

7、rexed (0.5 g/mL) shows typical apoptotic morphology, including nuclearshrinkage, fragmentation, chromatin condensation and apoptotic bodies in SGC7901 cells. Raltitrexed blocks the cellcycle at the G0/G1 phase, decreases in the mitochondrial membrane potential. Raltitrexed also increases the level o

8、fROS, induces caspase-3-dependent apoptosis via activation of the mitochondria, and increases TS protein and mRNAexpression levels3. Raltitrexed (1.5 nM) reduces the number of GM00637 cells, selectively induces gene conversions,but does not affect DSB-induced HR or NHEJ4.体内研究 Raltitrexed (0, 5, 10,

9、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 dUM

10、P levels2.PROTOCOLCell Assay 4 To assess the effect of Raltitrexed on cell viability and/or growth, GM00637 cells are plated into 25 cm2 flasks at adensity of 3.3105 cells per flask. Twenty four hours later, the medium is replaced with medium supplemented withvarious doses of Raltitrexed over a broa

11、d range of concentrations ranging from less than 1 nM to greater than 1 M.Three flasks of cells are used for each dose tested. Cells are exposed to Raltitrexed for 24 hours, at which time thecells are refed with medium containing no Raltitrexed. Forty-eight hours after feeding with drug-free medium,

12、 cellsare harvested and counted. The cell counts for the cells exposed to the various Raltitrexed doses are compared withthe cell count for control cells not exposed to Raltitrexed as a measure of the impact of Raltitrexed on cell viabilityand/or growth rate.MCE has not independently confirmed the a

13、ccuracy of these methods. They are for reference only.Animal The adult (7-8 week, 19-20 g) C57BL/6 mice are used in the experiment. Mice are maintained under 22C with a 12 hAdministration 2 light/day cycle and fed with standard mouse chow and tap water ad libitum. Female mice are mated with maleover

14、night and vaginal plugs are examined in the following morning. The presence of vaginal plug in the pregnantmice is considered as gestational day 0.5. Pregnant mice are randomly divided into 6 groups with 10 mice in eachgroup. Raltitrexed is dissolved in 0.9 % NaCl, and five groups are intraperitonea

15、lly injected with different doses ofRaltitrexed (5, 10, 11.5, 13.5, 15 mg/kg b/w) on gestational day 7.5. The control group is intraperitoneally injectedwith 0.9 % NaCl at the same volume on gestational day 7.5. On gestational day 11.5, pregnant mice are sacrificed,and embryos are examined under dis

16、sect microscope.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Page 2 of 3 www.MedChemE户使本产品发表的科研献 J Mol Med (Berl). 2019 Aug;97(8):1183-1193. Methods Mol Biol. 2018;1711:351-398.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFER

17、ENCES1. Zhao H, et al. Raltitrexed Inhibits HepG2 Cell Proliferation via G0/G1 Cell Cycle Arrest. Oncol Res. 2016;23(5):237-482. Dong Y, et al. Raltitrexeds effect on the development of neural tube defects in mice is associated with DNA damage, apoptosis, and proliferation. MolCell Biochem. 2015 Jan

18、;398(1-2):223-31.3. Xue S, et al. Raltitrexed induces mitochondrial-mediated apoptosis in SGC7901 human gastric cancer cells. Mol Med Rep. 2014 Oct;10(4):1927-34.4. Waldman BC, et al. Induction of intrachromosomal homologous recombination in human cells by raltitrexed, an inhibitor of thymidylate sy