(Synonyms: AS-1404, 5,6-MeXAA, NSC-640488, Vadimezan)
Catalog No.GC16280
DMXAA (Vadimezan) is a selective DT-diaphorase inhibitor with a Ki value of 20μM and an IC50 value of 62.5μM.
Product has been cited by 1 publications
Biochem Pharmacol (2025)：117516.PMID:41187884
Description
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-.
Protocol
Cell experiment [1]:
Cell lines
A549 cells
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.
Reaction Conditions
0.1, 1, and 10μM; 24h
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.
Animal experiment [2]:
Animal models
C57BL6/J mice
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.
Dosage form
25 mg/kg; i.p.
Applications
DMXAA(Vadimezan) protects C57BL/6J mice against influenza-induced weight lost, improved survival rate of mice.
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.
Chemical Properties
Cas No. 117570-53-3 SDF
Synonyms AS-1404, 5,6-MeXAA, NSC-640488, Vadimezan
Chemical Name 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
Formula C17H14O4 M.Wt 282.29
Solubility ≥7mg/ml in DMSO Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.
