1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEVadimezanCat. No.: HY-10964CAS No.: 117570-53-3Synonyms: ASA-404; DMXAA分式: CHO分量: 282.29作靶點(diǎn): STING; Interleukin Related作通路: Immunology/Inflammation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(shí)驗(yàn) 7

2、.5% sodium bicarbonate : 20 mg/mL (70.85 mM; Need ultrasonic)DMSO : 6.5 mg/mL (23.03 mM; Need ultrasonic and warming)H2O : 0.1 mg/mL (insoluble)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液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請根據(jù)產(chǎn)品

3、在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 Vadimezan (ASA-404; DMXAA)管破壞劑， 擾素 因 (STING) 刺激物，也 I型IFN和其他細(xì)胞因的強(qiáng)效誘導(dǎo)劑。IC50 & Target STING 1, type I IFNs 21/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE體外研究 Vadimezan (DMXAA), the vascular disrupting agent, is a murine agonist of the st

4、imulator of interferon genes(STING) and also a potent inducer of type I IFNs and other cytokines. Vadimezan (DMXAA) has nodetrimental effect on 344SQ-ELuc cell viability. It is found that Vadimezan-mediated up regulation of the NF-B pathway as shown by increased p65 phosphorylation in M2 macrophages

5、 1. Results demonstrate thatVadimezan (DMXAA)-treated cells are protected from VSV-induced cytotoxicity at all MOIs in contrast tomedium-pretreated macrophages. Vadimezan (DMXAA) effectively inhibits growth of both strains ofinfluenza, demonstrating the potential of Vadimezan for treatment of drug-r

6、esistant strains of humaninfluenza 2.體內(nèi)研究 344SQ-ELuc NSCLC subcutaneous tumors respond dramatically to Vadimezan (DMXAA), with a markeddecrease in bioluminescence (BLI) signals post-drug injection. Vadimezan (DMXAA) treatment of 344SQ-ELuc metastases yields no decrease in photon emission rates, with

7、 the tumors remaining histologicallysimilar to controls after this treatment. As with the large subcutaneous tumors, Vadimezan (DMXAA)administration to mice with small subcutaneous tumors still leads to 2-log decreases in photon emission atboth 6 and 24 hours 1. In vivo, Vadimezan (DMXAA) is a more

8、potent inducer of IFN- mRNA and arelatively poor inducer of TNF- mRNA. Vadimezan (DMXAA) administration leads to significantly less weightloss in influenza-infected mice 2.PROTOCOLKinase Assay 1 M2-polarized macrophages are treated with 20 g/mL Vadimezan (ASA-404) or DMSO vehicle for 30 min.Cells ar

9、e then lysed and protein denatured in SDS buffer and samples sent for RPPA analysis. Differentialabundance of various proteins and/or their phosphorylation status in response to Vadimezan (ASA-404) isassessed 1.MCE has not independently confirmed the accuracy of these methods. They are for reference

10、 only.Cell Assay 2 RAW 264.7 macrophages are cultured and plated at 1105 cells/well in a 96-well plate. After overnightincubation at 37C, cells are treated with medium containing vehicle or Vadimezan (DMXAA) (100 g/mL).After 6 h, the culture medium is replaced with serum-free DMEM containing VSV at

11、the indicated MOI for 1 h.Cells are then maintained in complete DMEM with 10% FBS. Twenty-four hours later, cells are washed withPBS, fixed with 10% buffered formalin, and rinsed thoroughly with distilled water. Adherent cells are stainedwith crystal violet 2.MCE has not independently confirmed the

12、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, 5105Administration 1 344SQ-ELuc cells in 100 L PBS are injected in both posterior flanks of mice. Tumor growth is monitoredevery 2 to 4 days via

13、BLI. Once tumors are established (day 10 for systemic metastases; day 7 or day 14 forsubcutaneous tumors), mice are given 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 methods. They ar

14、e for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn)2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE Gastroenterology. 2018 May;154(6):1822-1835.e2.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Downey CM, et al. DMXAA causes tumor site-specific vascular disruption in murine non-small cell lung

15、cancer, and like the endogenousnon-canonical cyclic dinucleotide STING agonist, 23-cGAMP, induces M2 macrophage repolarization. PLoS One. 2014 Jun18;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 invitro and in vivo. J Leukoc B