雷替曲塞作用機制 - Medchemexpress - MCE中國

1、Product Data SheetRaltitrexedCat. No.: HY-10821CAS No.: 112887-68-0分式: CHNOS分量: 458.49作靶點: Thymidylate Synthase; Nucleoside Antimetabolite/Analog作通路: Apoptosis; Cell Cycle/DNA Damage儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 29 mg/mL (63.25 mM)* means solu

2、ble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制備儲備液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請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲存時，請在 6 個內(nèi)使，-20C 儲存時，請

3、在 1 個內(nèi)使。體內(nèi)實驗請根據(jù)您的實驗動物和給藥式選擇適當?shù)娜芙獍浮Ｒ韵氯芙獍付颊埾劝凑?In Vitro 式配制澄清的儲備液，再依次添加助溶劑：為保證實驗結(jié)果的可靠性，澄 的儲備液可以根據(jù)儲存條件，適當保存；體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的式助溶1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.45 mM); Clear solution此案可獲得 2.5 mg/

4、mL (5.45 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.45 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 2.5 mg/mL (5.45 mM，飽和度未知) 的澄清溶液。以 1

5、mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合均勻。3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (5.45 mM); Clear solution此案可獲得 2.5 mg/mL (5.45 mM，飽和度未知) 的澄 溶液，此案不適于實驗周 期在半個以上的實驗。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Raltitre

6、xed種于化療的抗代謝藥物，通過抑制胸苷酸合成酶起作。體外研究 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.體內(nèi)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戶使本產(chǎn)品發(fā)表的科研獻 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