DMXAA (Vadimezan)
(Synonyms: 2,5-己酮可可碱,AS-1404, 5,6-MeXAA, NSC-640488, Vadimezan) 目录号 : GC16280
A STING activator and tumor vascular disrupting agent
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
| Cell experiment: [1] | |
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Cell lines |
HECPP cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
IC50: 500 μg/mL, 24 hours |
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Applications |
DMXAA did not induce mRNA for TNF or interferons in the HECPP cells. The mRNA of IP-10 was up-regulated following 2 h incubation with DMXAA at 400 μg/mL. Apoptotic cells were seen after 6 h incubation with DMXAA at this concentration. And the numbers increased with prolonged exposure. Apoptotic cell numbers at 24 h increased linearly with increasing dose of DMXAA above 100 μg/mL. The DMXAA concentration that induced 50% apoptosis after incubation for 24 h was 500 μg/mL. |
| Animal experiment: [2] | |
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Animal models |
Male 129/Sv mice injected with 344SQ-ELuc cells |
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Dosage form |
Intraperitoneal injection, 25 mg/kg |
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Applications |
Once tumors were established (day 7 or day 14 for subcutaneous tumors), mice were given 25 mg/kg of DMXAA by i.p. injection. BLI was carried out at 6 and 24 hours. 344SQ-ELuc NSCLC subcutaneous tumors respond dramatically to DMXAA, with a marked (~2-logs) decrease in bioluminescence (BLI) signals post-drug injection. The drop in BLI following DMXAA treatment was not due to direct tumor cell toxicity since DMXAA had no detrimental effect on 344SQ-ELuc cell viability. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Ching L M, Cao Z, Kieda C, et al. Induction of endothelial cell apoptosis by the antivascular agent 5, 6-dimethylxanthenone-4-acetic acid. British journal of cancer, 2002, 86(12): 1937-1942. [2] 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. PloS one, 2014, 9(6): e99988. |
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DMXAA (Vadimezan, AS-1404) is a selective inhibitor of DT-diaphorase with Ki50 and IC50 value of 20 μM and 62.5 μM, respectively [1, 2].
DT-diaphorase (DTD) is an obligate two-electron reductase and it has been reported that the expression of DTD is elevated in a variety of cancers [2].
DMXAA (Vadimezan) a potent DT-diaphorase inhibitor and is also reported as a multi-inhibitor for several kinases. When tested with sections of colon 38 tumors isolated from C57Bl/6 mice at different time, DMXAA (Vadimezan) (25 mg/kg) showed a high induction on endothelium cell apoptosis after 30 min treatment and showed intensely apoptotic vessels and large areas of necrosis of the tumor after 3 h treatment [2]. In NSCLC cell line A549 cells, DMXAA (Vadimezan) treatment arrested cell in G1 phase and induced cell apoptosis and autophagy by increasing cytosolic level of cytochrome and activation of caspase3 in a dose dependent manner from 0.1 μM to 10 μM [3].
In C57Bl/6 mice model with luciferase-expressing murine GL261 glioma cells subcutaneous xenograft, administration of DMXAA (Vadimezan) (25 mg/kg) resulted in widespread necrosis at 24 h, a 9-day growth delay and complete regressions in 50 % mice. Furthermore, co-administration of lenalidomide (100 mg/kg) significantly increased the growth delay to 20 days and the percentage of cures to 83 % [4].
It is reported that DMXAA (Vadimezan) is a multi-inhibitor to several kinases, with most potent effects being on members of the VEGFR (vascular endothelial growth factor receptor) tyrosine kinase family. In zebrafish embryos and HUVECs (human umbilical vein endothelial cells), DMXAA (Vadimezan) blocked the angiogenesis and VEGFR2 signalling [5].
References:
[1]. Phillips, R.M., 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. Biochem Pharmacol, 1999. 58(2): p. 303-10.
[2]. Ching, L.M., et al., Induction of endothelial cell apoptosis by the antivascular agent 5,6-Dimethylxanthenone-4-acetic acid. Br J Cancer, 2002. 86(12): p. 1937-42.
[3]. 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. Drug Des Devel Ther, 2015. 9: p. 937-68.
[4]. Yung, R., et al., Efficacy against subcutaneous or intracranial murine GL261 gliomas in relation to the concentration of the vascular-disrupting agent, 5,6-dimethylxanthenone-4-acetic acid (DMXAA), in the brain and plasma. Cancer Chemother Pharmacol, 2014. 73(3): p. 639-49.
[5]. Buchanan, C.M., et al., DMXAA (Vadimezan, ASA404) is a multi-kinase inhibitor targeting VEGFR2 in particular. Clin Sci (Lond), 2012. 122(10): p. 449-57.
| 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。