安吖啶作用機(jī)制 - Medchemexpress - MCE中國

1、Product Data SheetAmsacrineCat. No.: HY-13551CAS No.: 51264-14-3分式: CHNOS分量: 393.46作靶點: Topoisomerase; Autophagy作通路: Cell Cycle/DNA Damage; Autophagy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 : 9.3 mg/mL (23.64 mM; Need ultrasonic and warming)SolventMass1 mg

2、 5 mg 10 mgConcentration制備儲備液1 mM 2.5416 mL 12.7078 mL 25.4155 mL5 mM 0.5083 mL 2.5416 mL 5.0831 mL10 mM 0.2542 mL 1.2708 mL 2.5416 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(dāng)?shù)娜芙獍?。以下溶解案都請?/p>

3、按照 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(dāng)保存；體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當(dāng)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 (6.35 mM); Clear solution此案可獲得 2.5 mg/mL (6.35 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 1

4、00 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。BIOLOGICAL ACTIVITYPage 1 of 2 www.MedChemE物活性 Amsacrine (m-AMSA; acridinyl anisidide)腫瘤細(xì)胞 DNA 嵌劑，還能抑制拓?fù)洚悩?gòu)酶 II。IC & Target Topoisomerase II體外研究 Amsacrine (m-AMSA) blocks HERG currents in HEK 293 cells a

5、nd Xenopus oocytes in a concentration-dependentmanner, with IC50 values of 209.4 nm and 2.0 M, respectively. Amsacrine (m-AMSA) causes a negative shift in thevoltage dependence of both activation (7.6 mV) and inactivation (7.6 mV). HERG current block by amsacrine isnot frequency dependent1. In vitro

6、 studies of normal human lymphocytes with various concentrations ofAmsacrine (m-AMSA), show both increased levels of chromosomal aberrations, ranging from 8% to 100%, andincrease SCEs, ranging from 1.5 times the normal at the lowest concentration studied (0.005 g/mL) to 12 times thenormal (0.25 g/mL

7、)3. Amsacrine (m-AMSA)-induced apoptosis of U937 cells is characterized by caspase-9 andcaspase-3 activation, increased intracellular Ca2+ concentration, mitochondrial depolarization, and MCL1 down-regulation. Amsacrine (m-AMSA) induces MCL1 down-regulation by decreasing its stability. Further, amsa

8、crine-treated U937 cells show AKT degradation and Ca2+-mediated ERK inactivation4.體內(nèi)研究 In animals treated with different doses of amsacrine (0.5-12 mg/kg), the frequencies of micronucleatedpolychromatic erythrocytes increase significantly after treatment with 9 and 12 mg/kg. Furthermore, the present

9、 study demonstrates for the first time that Amsacrine (m-AMSA) has high incidences of clastogenicity and lowincidences of aneugenicity whereas nocodazole has high incidences of aneugenicity and low incidences ofclastogenicity during mitotic phases in vivo2.PROTOCOLAnimal Amsacrine (m-AMSA) is invest

10、igated in three separated experiments. In the first experiment, animals are treated byAdministration 2 intraperitoneal injection with 0.5, 1.5 and 4.5 mg/kg of amsacrine and bone marrow is sampled 24 h after treatment.Preliminary negative MN results at this sampling time lead to the use of 30 h samp

11、ling time for amsacrine. Thus, inthe second experiment, mice are treated with 0.5, 1.5 and 4.5 mg/kg of Amsacrine (m-AMSA) and bone marrow issampled 30 h after treatment. The doses and sampling times for amsacrine are chosen by reference to earlier studiesand the selected doses are within the dose r

12、ange used for human chemotherapy. The results again show that themicronuclei frequency in the bone marrow of mice is not affected by treatment with any of the selected doses of thetest agent, at 30 h sampling time, thus, in the third experiment, mice are treated with 6, 9 and 12 mg/kg of amsacrinean

13、d bone marrow is sampled 24 and 30 h after treatment.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) J Mol Med (Berl). 2019 Aug;97(8):1183-1193.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Thomas D, et al.

14、 Inhibition of cardiac HERG currents by the DNA topoisomerase II inhibitor amsacrine: mode of action. Br J Pharmacol. 2004Jun;142(3):485-94.2. Attia SM. Molecular cytogenetic evaluation of the mechanism of genotoxic potential of amsacrine and nocodazole in mouse bone marrow cells. J ApplToxicol. 201

15、3 Jun;33(6):426-33.Page 2 of 3 www.MedChemE3. Kao-Shan CS, et al. Cytogenetic effects of amsacrine on human lymphocytes in vivo and in vitro. Cancer Treat Rep. 1984 Jul-Aug;68(7-8):989-97.4. Lee YC, et al. Amsacrine-induced apoptosis of human leukemia U937 cells is mediated by the inhibition of AKT- and ERK-induced stabilization of MCL1.Apoptosis. 2016