DMXAA (Vadimezan)
(Synonyms: 2,5-己酮可可碱,AS-1404, 5,6-MeXAA, NSC-640488, Vadimezan) 目录号 : GC16280
DMXAA (Vadimezan)是一种选择性的DT-心肌黄酶抑制剂，Ki值为20μM，IC50值为62.5μM。
Cas No.:117570-53-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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Cell experiment [1]: |
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Cell lines |
A549 cells |
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Preparation method |
A549 cells were treated with DMXAA(Vadimezan) at concentrations of 0.1, 1, and 10μM for 24 hours.The effect of treatment with DMXAA(Vadimezan) on the cell cycle was determined by flow cytometry. |
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Reaction Conditions |
0.1, 1, and 10μM; 24h |
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Applications |
A concentration-dependent increase in the cell number in G1 phase was observed after incubation of A549 cells with DMXAA(Vadimezan) at 0.1, 1, and 10 μM for 24h. |
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Animal experiment [2]: |
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Animal models |
C57BL6/J mice |
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Preparation method |
mice were injected i.p. with 0.5ml DMXAA(Vadimezan)(25 mg/kg). After 3h, mice were anesthetized with isoflurane and infected i.n. with 50μL PR8 influenza. Give a certain dose of saline or DMXAA (Vadimezan) 48 hours after the second intraperitoneal injection. Survival was monitored daily for 14 days. Weight loss was monitored on individual mice after infection. |
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Dosage form |
25 mg/kg; i.p. |
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Applications |
DMXAA(Vadimezan) protects C57BL/6J mice against influenza-induced weight lost, improved survival rate of mice. |
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References: [1]Zhou S F , Pan S T , Zhou Z W ,et al.Proteomic response to 5,6-dimethylxanthenone 4-acetic acid (DMXAA, vadimezan) in human non-small cell lung cancer A549 cells determined by the stable-isotope labeling by amino acids in cell culture (SILAC) approach[J].Drug Design Development & Therapy, 2015. [2]Shirey K A , Nhu Q M , Yim K C , et al. The anti-tumor agent, 5,6-dimethylxanthenone-4-acetic acid (DMXAA), induces IFN-beta-mediated antiviral activity in vitro and in vivo.[J].Journal of Leukocyte Biology, 2011, 89. |
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DMXAA (Vadimezan) is a selective DT-diaphorase inhibitor with a Ki value of 20μM and an IC50 value of 62.5μM[1]. DMXAA (Vadimezan) is a tumor blood vessel disrupting agent (tumor-VDA) that induces rapid closure of blood flow in tumors to cause tumor regression[2]. DMXAA (Vadimezan) is an agonist of stimulator of interferon genes (STING) and a potent inducer of type I IFN and other cytokines[3]. DMXAA (Vadimezan) is also a multi-kinase inhibitor, specifically targeting VEGFR 2 [4].
In vitro, DMXAA (Vadimezan) (500 μg/mL) treated HECPP cells for 24 hours, inducing 50% cell apoptosis and up-regulating IP-10 mRNA levels [5]. DMXAA (Vadimezan) (0.1μM-10μM) induced G1 arrest in A549 cells in a dose-dependent manner, thereby inducing apoptosis and autophagy, and also increased beclin1 and microtubule-associated protein 1A/1B-light chain in the cells. 3 (LC 3-II) expression is enhanced [6].
In vivo, DMXAA (Vadimezan) (25 mg/kg; i.p.) significantly improved survival and reduced influenza-induced weight loss in C57BL/6J mice infected with H1N1 influenza virus, resulting in a survival rate of 60%, compared with control survival only 20%[7]. DMXAA(Vadimezan) (25mg/kg) administered to mice via intraperitoneal injection significantly reduced the bioluminescence (BLI) signal in subcutaneous tumor cells, and necrosis occurred around the tumor without bleeding [8].
References:
[1] Phillips RM. Inhibition of DT-diaphorase (NAD(P)H:quinone oxidoreductase, EC 1.6.99.2) by 5,6-dimethylxanthenone-4-acetic acid (DMXAA) and flavone-8-acetic acid (FAA): implications for bioreductive drug development..[J] Biochem Pharmacol. 1999 Jul 15;58(2):303-10.
[2] Adli A D F , Jahanban-Esfahlan R , Seidi K , et al. An overview on Vadimezan (DMXAA): The vascular disrupting agent.[J]. Chem Biol Drug Des, 2018(5).
[3]Downey C M, Aghaei M, Schwendener R A, et al. DMXAA causes tumor site-specific vascular disruption in murine non-small cell lung cancer, and like the endogenous non-canonical cyclic dinucleotide STING agonist, 2′ 3′-cGAMP, induces M2 macrophage repolarization[J]. PloS one, 2014, 9(6): e99988.
[4]Buchanan CM, Shih JH, Astin JW, et al. DMXAA (Vadimezan, ASA404) is a multi-kinase inhibitor targeting VEGFR2 in particular.[J]Clin Sci (Lond). 2012 May 1;122(10):449-57.
[5]Ching L M, Cao Z, Kieda C, et al. Induction of endothelial cell apoptosis by the antivascular agent 5, 6-dimethylxanthenone-4-acetic acid[J]. British journal of cancer, 2002, 86(12): 1937-1942.
[6]Zhou S F , Pan S T,et al.Proteomic response to 5,6-dimethylxanthenone 4-acetic acid (DMXAA, vadimezan) in human non-small cell lung cancer A549 cells determined by the stable-isotope labeling by amino acids in cell culture (SILAC) approach[J].Drug Design Development & Therapy, 2015.
[7]Shirey K A , Nhu Q M , Yim K C , et al. The anti-tumor agent, 5,6-dimethylxanthenone-4-acetic acid (DMXAA), induces IFN-beta-mediated antiviral activity in vitro and in vivo.[J].Journal of Leukocyte Biology, 2011, 89.
[8] Downey C M , Mehrnoosh A , Schwendener R A ,et al.DMXAA Causes Tumor Site-Specific Vascular Disruption in Murine Non-Small Cell Lung Cancer, and like the Endogenous Non-Canonical Cyclic Dinucleotide STING Agonist, 2′3′-cGAMP, Induces M2 Macrophage Repolarization[J].PLoS ONE, 2014, 9(6):e99988-.
DMXAA (Vadimezan)是一种选择性的DT-心肌黄酶抑制剂，Ki值为20μM，IC50值为62.5μM[1]。DMXAA (Vadimezan)是一种肿瘤血管破坏剂（肿瘤-VDA），可诱导肿瘤中的血流快速关闭以引起肿瘤消退[2]。DMXAA (Vadimezan)是干扰素基因刺激因子（STING）的激动剂，也是I型IFN和其他细胞因子的有效诱导剂[3]。DMXAA (Vadimezan)也是一种多激酶抑制剂，特别是靶向VEGFR 2[4]。
在体外，DMXAA (Vadimezan)（500 μg/mL）处理HECPP细胞24h，诱导了50% 细胞凋亡，上调了IP-10的mRNA水平[5]。DMXAA (Vadimezan)（0.1μM-10μM）以剂量依赖性方式诱导了A549细胞G1期阻滞，从而诱导细胞凋亡和自噬，还使细胞中的beclin1和微管相关蛋白1A/1B-轻链3（LC 3-II）的表达增强[6]。
在体内，DMXAA (Vadimezan) (25 mg/kg; i.p.)显著提高了感染H1N1流感病毒的C57BL/6J小鼠存活率，减少流感引起的体重减轻，使存活率达60%, 而对照组存活率仅为20%[7]。DMXAA (Vadimezan) (25 mg/kg)通过腹腔注射给予小鼠，显著降低了皮下肿瘤细胞中生物发光（BLI）信号，肿瘤周边发生坏死且不存在出血[8]。
| Cas No. | 117570-53-3 | SDF | |
| 别名 | 2,5-己酮可可碱,AS-1404, 5,6-MeXAA, NSC-640488, Vadimezan | ||
| 化学名 | 2-(5,6-dimethyl-9-oxoxanthen-4-yl)acetic acid | ||
| Canonical SMILES | CC1=C(C2=C(C=C1)C(=O)C3=C(O2)C(=CC=C3)CC(=O)O)C | ||
| 分子式 | C17H14O4 | 分子量 | 282.29 |
| 溶解度 | ≥ 14.1mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.5425 mL | 17.7123 mL | 35.4246 mL |
| 5 mM | 0.7085 mL | 3.5425 mL | 7.0849 mL |
| 10 mM | 0.3542 mL | 1.7712 mL | 3.5425 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。