絲裂霉素 C作用機制 - Medchemexpress - MCE中國

1、Product Data SheetMitomycin CCat. No.: HY-13316CAS No.: 50-07-7分式: CHNO分量: 334.33作靶點: DNA Alkylator/Crosslinker; DNA/RNA Synthesis; ADC Cytotoxin; Bacterial;Apoptosis作通路: Cell Cycle/DNA Damage; Antibody-drug Conjugate/ADC Related; Anti-infection;Apoptosis儲存式: 4C, protect from light* In solvent : -80

2、C, 6 months; -20C, 1 month (protect from light)溶解性數(shù)據(jù)體外實驗 DMSO : 50 mg/mL (149.55 mM; Need ultrasonic)H2O : 1 mg/mL (2.99 mM; ultrasonic and warming and heat to 60C)SolventMass1 mg 5 mg 10 mgConcentration制備儲備液1 mM 2.9911 mL 14.9553 mL 29.9106 mL5 mM 0.5982 mL 2.9911 mL 5.9821 mL10 mM 0.2991 mL 1.4955

3、 mL 2.9911 mL請根據(jù)產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，避免反復凍融造成的產品失效。儲備液的保存式和期限：-80C, 6 months; -20C, 1 month (protect from light)。-80C 儲存時，請在 6 個內使，-20C 儲存時，請在 1 個內使。體內實驗請根據(jù)您的實驗動物和給藥式選擇適當?shù)娜芙獍?。以下溶解案都請先按?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

4、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: 2.17 mg/mL (6.49 mM); Clear solution此案可獲得 2.17 mg/mL (6.49 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 21.7 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.

5、請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.17 mg/mL (6.49 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 2.17 mg/mL (6.49 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 21.7 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。BIOLOGICAL ACTIVITY物活性 Mitomycin C (Ametycine) 種 DNA 交聯(lián)劑 (DNA cross-

6、linking agent)，誘導 DNA 損傷。Mitomycin C 種抗腫 瘤化合物和抗素，可有效的抑制 DNA 合成 (DNA synthesis)。Mitomycin C 種 ADC 毒性分 (ADC Cytotoxin) ，可以誘導凋亡 (Apoptosis) 作。IC & Target Traditional Cytotoxic Agents體外研究 The HCT116 (p53-/-) cells are minimally sensitive to either Mitomycin C (Ametycine) or TRAIL alone. However,surprisi

7、ngly, combination treatment with MMC and TRAIL decreases cell viability significantly. Although Mitomycin Cand TRAIL alone are moderately effective, Mitomycin C substantially enhances the effect of TRAIL on suppression ofthe cell proliferation. Mitomycin C and TRAIL treatment alone induces 9.5% and

8、35.0% apoptosis, respectively.However, combination treatment with Mitomycin C and TRAIL enhances apoptosis to 66.6%1.Mitomycin C is a cytotoxic chemotherapeutic agent that causes DNA damage in the form of DNA cross-links as wellas a variety of DNA monoadducts and is known to induce p532.體內研究 Mice be

9、aring xenografted HCT116 (p53-/-) colon tumors and HT-29 colon tumors are treated with Mitomycin C(Ametycine; i.p., 1 mg/kg) and TRAIL (i.v., 100 g) every other day. Animals are treated with 10 consecutive cycles ofthe combination therapy regimen. The combination therapy suppresses tumor growth sign

10、ificantly and does notimpact the weight of the mice, indicating that the therapeutic combination of Mitomycin C and TRAIL is well-tolerated and has anti-tumor activity in vivo1.Intravesical Mitomycin C instillations has an effect on body weight. After 3 consecutive weekly instillations of 1mg/mL Mit

11、omycin C there is almost no weight gain, whereas rats in the other 3 groups has a statistically significantweight gain compared with MMC treated rats3.PROTOCOLCell Assay 1 Colon adenocarcinoma HCT116 and HT-29 human colon cancer cells are used. The CellTiter-Glo Luminescent CellViability Assay is us

12、ed to measure cell viability, which use a unique, stable form of luciferase to measure ATP as anindicator of viable cells, and the luminescent signal produced is proportional to the number of viable cells present inculture. Cells are pretreated with Mitomycin C (5 M) for 12 h or 24 h, and then expos

13、ed to different concentrationsof TRAIL for 12 h. An equal volume (100 L) of CellTiter-GloTM reagent is added and the solution is mixed gently for 2min on an orbital shaker. Mixture is incubated at room temperature for 10 min to allow luminescent signal tostabilize, and then imaging is performed usin

14、g the Xenogen IVIS system to quantify the cell viability1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice1Administration 13 Four- to 6-wk-old NCr nude mice are treated with Mitomycin C (1 mg/kg) by intraperitoneal injection for 24 h,followed

15、 by one intravenous dose of purified rhTRAIL (100 g). As a negative control, a subset of the mice areinjected (i.p. and i.v.) with saline (vehicle) at the same frequency of treatment. Animals are treated for 3 consecutiveweeks. The tumor size is monitored every week using caliper measurements of the

16、 tumor volume.Rats3Young adult female Wistar rats at age 13 weeks with a median weight of 217 g (range 187 to 255) are randomizedPage 2 of 3 www.MedChemEinto 4 groups of 10 each, namely a normal group with no instillations, an NaCl 0.9% or placebo group that receivedinstillations with the solvent of

17、 the chemotherapeutic agent, Mitomycin C (1 mg/mL) group.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產品發(fā)表的科研獻 Nat Microbiol. 2018 Nov;3(11):1266-1273. Proc Natl Acad Sci U S A. 2019 Jun 18;116(25):12147-12152. J Hematol Oncol. 2018 Aug 13;11(1):1

18、02. J Hematol Oncol. 2018 Mar 20;11(1):44. New Phytol. 2018 Oct;220(2):476-487.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Cheng H, et al. Mitomycin C potentiates TRAIL-induced apoptosis through p53-independent upregulation of death receptors: Evidence for the role of c-Jun N-terminal kinase activation. Cell Cycle. 2012 Sep 1;11(17): 3312-23.2. Abbas T, et al. Differential activation of p53 by the various adducts of mitomycin C. J Biol Chem. 2002 Oct 25;277(43):40513-9.3. Michielsen D, et al. Mitomycin C: functional bladder damage in rats after r