2,5-己酮可可堿作用機(jī)制 - Medchemexpress - MCE中國

1、Product Data SheetVadimezanCat. No.: HY-10964CAS No.: 117570-53-3分式: CHO分量: 282.29作靶點(diǎn): STING; Interleukin Related; Influenza Virus作通路: Immunology/Inflammation; Anti-infection儲(chǔ)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(shí)驗(yàn) 7.5% sodium bicarbonate : 20 mg/mL (70.85 mM;

2、Need ultrasonic)DMSO : 7.14 mg/mL (25.29 mM; Need ultrasonic)H2O : 0.1 mg/mL (insoluble)SolventMass1 mg 5 mg 10 mgConcentration制備儲(chǔ)備液1 mM 3.5425 mL 17.7123 mL 35.4246 mL5 mM 0.7085 mL 3.5425 mL 7.0849 mL10 mM 0.3542 mL 1.7712 mL 3.5425 mL請(qǐng)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(chǔ)備液；旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存式和期

3、限：-80C, 6 months; -20C, 1 month。-80C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?6 個(gè)內(nèi)使，-20C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?1 個(gè)內(nèi)使。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍?。以下溶解案都?qǐng)先按照 In Vitro 式配制澄清的儲(chǔ)備液，再依次添加助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄 的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)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(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubil

4、ity: 0.71 mg/mL (2.52 mM); Clear solution此案可獲得 0.71 mg/mL (2.52 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 7.1 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合均勻。2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 0.71 mg/mL (2.52 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 0.71 mg/mL (2.52 mM，飽和度未知) 的澄 溶液，

5、此案不適于實(shí)驗(yàn)周 期在半個(gè)以上的實(shí)驗(yàn)。以 1 mL 作液為例，取 100 L 7.1 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Vadimezan (DMXAA; ASA-404) 管破壞劑， 擾素 誘導(dǎo)劑。Vadimezan 具有抗流感病毒 H1N1-PR8 的活性。因 (STING) 刺激物，也 I 型 IFN 和其他細(xì)胞因的強(qiáng)效IC & Target STING1, type I IFNs2體外研究 Vadimezan (DMXAA), the vascular disrupting agent, is a muri

6、ne agonist of the stimulator of interferon genes (STING)and also a potent inducer of type I IFNs and other cytokines. Vadimezan (DMXAA) has no detrimental effect on344SQ-ELuc cell viability. It is found that Vadimezan-mediated up regulation of the NF-B pathway as shown byincreased p65 phosphorylatio

7、n in M2 macrophages1. Results demonstrate that Vadimezan (DMXAA)-treated cellsare protected from VSV-induced cytotoxicity at all MOIs in contrast to medium-pretreated macrophages. Vadimezan(DMXAA) effectively inhibits growth of both strains of influenza, demonstrating the potential of Vadimezan fort

8、reatment of drug-resistant strains of human influenza2.體內(nèi)研究 344SQ-ELuc NSCLC subcutaneous tumors respond dramatically to Vadimezan (DMXAA), with a marked decrease inbioluminescence (BLI) signals post-drug injection. Vadimezan (DMXAA) treatment of 344SQ-ELuc metastases yieldsno decrease in photon emi

9、ssion rates, with the tumors remaining histologically similar to controls after this treatment.As with the large subcutaneous tumors, Vadimezan (DMXAA) administration to mice with small subcutaneous tumorsstill leads to 2-log decreases in photon emission at both 6 and 24 hours1. In vivo, Vadimezan (

10、DMXAA) is a morepotent inducer of IFN- mRNA and a relatively poor inducer of TNF- mRNA. Vadimezan (DMXAA) administrationleads to significantly less weight loss in influenza-infected mice2.PROTOCOLKinase Assay 1 M2-polarized macrophages are treated with 20 g/mL Vadimezan (ASA-404) or DMSO vehicle for

11、 30 min. Cells arethen lysed and protein denatured in SDS buffer and samples sent for RPPA analysis. Differential abundance of variousproteins and/or their phosphorylation status in response to Vadimezan (ASA-404) is assessed1.MCE has not independently confirmed the accuracy of these methods. They a

12、re for reference only.Cell Assay 2 RAW 264.7 macrophages are cultured and plated at 1105 cells/well in a 96-well plate. After overnight incubation at37C, cells are treated with medium containing vehicle or Vadimezan (DMXAA) (100 g/mL). After 6 h, the culturemedium is replaced with serum-free DMEM co

13、ntaining VSV at the indicated MOI for 1 h. Cells are then maintained incomplete DMEM with 10% FBS. Twenty-four hours later, cells are washed with PBS, fixed with 10% buffered formalin,and rinsed thoroughly with distilled water. Adherent cells are stained with crystal violet2.MCE has not independentl

14、y confirmed the accuracy of these methods. They are for reference only.Animal Male 129/Sv mice (6 to 12 week old) are used in this study. To generate subcutaneous tumors, 5105 344SQ-ELucAdministration 1 cells in 100 L PBS are injected in both posterior flanks of mice. Tumor growth is monitored every

15、 2 to 4 days via BLI.Once tumors are established (day 10 for systemic metastases; day 7 or day 14 for subcutaneous tumors), mice aregiven 25 mg/kg of Vadimezan (DMXAA), or DMSO vehicle by i.p. injection. BLI is carried out at 6 and 24 hours 1.MCE has not independently confirmed the accuracy of these

16、 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(xiàn) Gastroenterology. 2018 May;154(6):1822-1835.e2. Sci China Chem. 2020 Mar.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Downey CM, et al. DMXAA causes tumor site-specific vascular disruption i

17、n murine non-small cell lung cancer, and like the endogenous non-canonicalcyclic dinucleotide STING agonist, 23-cGAMP, induces M2 macrophage repolarization. PLoS One. 2014 Jun 18;9(6):e99988.2. Shirey KA, et al. The anti-tumor agent, 5,6-dimethylxanthenone-4-acetic acid (DMXAA), induces IFN-beta-mediated antiviral activity in vitro and in vivo. JLeukoc Biol. 2011 Mar;89(3):351-7.3. Shirey KA, et al. The anti-tumor agent, 5,6-dimethylxanthenone-4-acetic acid (DMXAA), induces IFN-beta-mediated antiviral activity in vitro a