Home Angiogenesis VDA chemical - STING agonist - TNF-alpha modulator - Antiviral inhibitor - IFN activator Vadimezan (DMXAA) For research use only.

Vadimezan (DMXAA)

Synonyms: ASA404, NSC 640488

Vadimezan (DMXAA) is a vascular disrupting agents (VDA) and competitive inhibitor of DT-diaphorase with Ki of 20 μM and IC50 of 62.5 μM in cell-free assays, respectively. DMXAA (Vadimezan) is also a STING agonist with potential antineoplastic activity. DMXAA (Vadimezan) potently induces IFN-β but relatively low TNF-α expression in vitro. DMXAA (Vadimezan) has antiviral activity. Phase 3.

Vadimezan (DMXAA) Chemical Structure

Vadimezan (DMXAA) Chemical Structure

CAS No. 117570-53-3

Purity & Quality Control

Vadimezan (DMXAA) Related Products

Signaling Pathway

VDA Signaling Pathways

VDA Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human BJ cells Cytotoxic assay 24 h Cytotoxicity against human BJ cells after 24 hrs by MTT assay, CC50=48.9 μM 24518295
HECPP cells Function assay 10 ug/mL Activation of NF-kappaB in HECPP cells at 10 ug/mL 17616114
MCF7 Antiproliferative assay 24 hrs Antiproliferative activity against human MCF7 cells co-treated with pyranoxanthone at 1:1 molar ratio after 24 hrs by MTT assay, IC50 = 11.89 μM. 29129511
MDA-MB-231 Antiproliferative assay 24 hrs Antiproliferative activity against human MDA-MB-231 cells co-treated with pyranoxanthone at 1:1 molar ratio after 24 hrs by MTT assay, IC50 = 12.12 μM. 29129511
K562 Antiproliferative assay 24 hrs Antiproliferative activity against human K562 cells co-treated with pyranoxanthone at 1:1 molar ratio after 24 hrs by MTT assay, IC50 = 19.14 μM. 29129511
HepG2 Antiproliferative assay 24 hrs Antiproliferative activity against human HepG2 cells co-treated with pyranoxanthone at 1:1 molar ratio after 24 hrs by MTT assay, IC50 = 21.25 μM. 29129511
COLO320 Antiproliferative assay 48 hrs Antiproliferative activity against human COLO320 cells after 48 hrs by CCK8 assay, IC50 = 39.5 μM. 28376372
MDA-MB-231 Antiproliferative assay 48 hrs Antiproliferative activity against human MDA-MB-231 cells after 48 hrs by CCK8 assay, IC50 = 48.4 μM. 28376372
MDA-MB-231 Growth inhibition assay 24 hrs Growth inhibition of human MDA-MB-231 cells after 24 hrs by MTT assay, IC50 = 48.42 μM. 29609121
MDA-MB-231 Antiproliferative assay 24 hrs Antiproliferative activity against human MDA-MB-231 cells after 24 hrs by MTT assay, IC50 = 48.44 μM. 29129511
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells 29435139
MG 63 (6-TG R) qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
MDA-MB-231 Apoptosis assay 24 to 96 uM 48 hrs Induction of apoptosis in human MDA-MB-231 cells assessed as increase in cleaved caspase-3 expression at 24 to 96 uM after 48 hrs by Western blot analysis 28376372
MDA-MB-231 Apoptosis assay 24 to 96 uM 48 hrs Induction of apoptosis in human MDA-MB-231 cells assessed as increase in cleaved PARP level at 24 to 96 uM after 48 hrs by Western blot analysis 28376372
MDA-MB-231 Function assay 24 to 96 uM 48 hrs Decrease in caspase-3 level in human MDA-MB-231 cells at 24 to 96 uM after 48 hrs by Western blot analysis 28376372
MDA-MB-231 Function assay 24 to 96 uM 48 hrs Increase in p53 level in human MDA-MB-231 cells at 24 to 96 uM after 48 hrs by Western blot analysis 28376372
MDA-MB-231 Function assay 24 to 96 uM 48 hrs Decrease in caspase-9 level in human MDA-MB-231 cells at 24 to 96 uM after 48 hrs by Western blot analysis 28376372
MDA-MB-231 Function assay 24 to 96 uM 48 hrs Decrease in MDM2 level in human MDA-MB-231 cells at 24 to 96 uM after 48 hrs by Western blot analysis 28376372
HepG2 Cell cycle arrest assay 0.2 uM 24 hrs Cell cycle arrest in human HepG2 cells assessed as accumulation at S phase at 0.2 uM after 24 hrs by propidium iodide staining-based flow cytometric method relative to control 29129511
HepG2 Cell cycle arrest assay 24 hrs Cell cycle arrest in human HepG2 cells assessed as accumulation at S phase co-treated with pyranoxanthone at 1:1 molar ratio after 24 hrs by propidium iodide staining-based flow cytometric method 29129511
HepG2 Apoptosis assay 0.2 uM 24 hrs Induction of apoptosis in human HepG2 cells assessed as increase in cleaved caspase-3 levels at 0.2 uM after 24 hrs by Western blot method 29129511
HepG2 Apoptosis assay 0.2 uM 24 hrs Induction of apoptosis in human HepG2 cells assessed as increase in cleaved caspase-9 levels at 0.2 uM after 24 hrs by Western blot method 29129511
HepG2 Apoptosis assay 24 hrs Induction of apoptosis in human HepG2 cells assessed as increase in cleaved PARP levels co-treated with pyranoxanthone at 1:1 molar ratio after 24 hrs by Western blot method 29129511
HepG2 Apoptosis assay 0.2 uM 24 hrs Induction of apoptosis in human HepG2 cells assessed as increase in cleaved PARP levels at 0.2 uM after 24 hrs by Western blot method 29129511
HepG2 Apoptosis assay 24 hrs Induction of apoptosis in human HepG2 cells assessed as increase in cleaved caspase-3 levels co-treated with pyranoxanthone at 1:1 molar ratio after 24 hrs by Western blot method 29129511
HepG2 Apoptosis assay 24 hrs Induction of apoptosis in human HepG2 cells assessed as increase in cleaved caspase-9 levels co-treated with pyranoxanthone at 1:1 molar ratio after 24 hrs by Western blot method 29129511
HepG2 Apoptosis assay 24 hrs Induction of apoptosis in human HepG2 cells assessed as downregulation of Bcl-xL expression co-treated with pyranoxanthone at 1:1 molar ratio after 24 hrs by Western blot method 29129511
HepG2 Apoptosis assay 24 hrs Induction of apoptosis in human HepG2 cells assessed as upregulation of Bid expression co-treated with pyranoxanthone at 1:1 molar ratio after 24 hrs by Western blot method 29129511
Click to View More Cell Line Experimental Data

Biological Activity

Description Vadimezan (DMXAA) is a vascular disrupting agents (VDA) and competitive inhibitor of DT-diaphorase with Ki of 20 μM and IC50 of 62.5 μM in cell-free assays, respectively. DMXAA (Vadimezan) is also a STING agonist with potential antineoplastic activity. DMXAA (Vadimezan) potently induces IFN-β but relatively low TNF-α expression in vitro. DMXAA (Vadimezan) has antiviral activity. Phase 3.
Targets
DT-diaphorase [1]
(Cell-free assay)		 DT-diaphorase [1]
(Cell-free assay)
20 μM(Ki) 20 μM(Ki)
In vitro
In vitro In DLD-1 human colon carcinoma cells, DMXAA inhibits DT-diaphorase activity without significant effects on the activity of cytochrome b5 reductase and cytochrome P450 reductase. Combination of menadione and DMXAA leads to an increase in the antiproliferative activity of DLD-1 cells. [1] DMXAA, as an antiviral agent, inhibits VSV-induced cytotoxicity and influenza virus replication in RAW 264.7 macrophages. [2] A recent study shows that DMXAA has non-immune-mediated inhibitory effects against several kinase members of VEGFR (vascular endothelial growth factor receptor), such as VEGFR2 signalling in human umbilical vein endothelial cells. [3]
Kinase Assay DT-diaphorase activity and kinetic analysis of enzyme inhibition
Purified DT-diaphorase enzyme activity is assayed by measuring the reduction of cytochrome c at 550 nm on a Beckman DU 650 spectrophotometer. Each assay contains cytochrome c (70 μM), NADH (variable concentrations), purified DT-diaphorase (0.032 μg), and menadione (variable concentrations) in a final volume of 1 mL Tris–HCl buffer (50 mM, pH 7.4) containing 0.14% BSA. The reaction is started by the addition of NADH. Rates of reduction are calculated over the initial part of the reaction curve (30 seconds), and results are expressed in terms of μmol cytochrome c reduced/min/mg protein using a molar extinction coefficient of 21.1 mM−1 cm−1 for reduced cytochrome c. Enzyme assays are carried out at room temperature and all reactions are performed in triplicate. Inhibition of purified DT-diaphorase activity is performed by the inclusion of DMXAA (at various concentrations) in the reaction, and inhibition characteristics are determined by varying the concentration of NADH (constant menadione) or menadione (constant NADH) at several concentrations of inhibitor. Ki values are obtained by plotting 1/V against. The activity of DT-diaphorase in DLD-1 cells is determined by measuring the dicumarol-sensitive reduction of DCPIP at 600 nm. Briefly, DLD-1 cells in mid-exponential growth are harvested by scraping into ice-cold buffer (Tris–HCl, 25 mM, pH 7.4 and 250 mM sucrose) and sonicated on ice. Enzyme assay conditions are 2 mM NADH, 40 μM DCPIP, 20 μL of dicumarol (when required) in a final volume of 1 mL Tris–HCl (25 mM, pH 7.4) containing BSA (0.7 mg/mL). Results are expressed as the dicumarol-sensitive reduction of DCPIP using a molar extinction coefficient of 21 mM−1 cm−1. Protein levels are determined using the Bradford assay
Cell Research Cell lines DLD-1 and H460 cells
Concentrations 0-2 mM
Incubation Time 96 hours
Method DLD-1 human colon carcinoma and H460 human non-small cell lung carcinoma cells are routinely maintained as monolayer cultures in RPMI 1640 culture medium supplemented with foetal calf serum (10%), sodium pyruvate (2 mM), penicillin/streptomycin (50 IU mL−1/50 μg mL-1) and l-glutamine (2 mM). Chemosensitivity is assessed using the MTT assay and all assays are performed under aerobic conditions. Briefly, cells are plated into each well of a 96-well culture plate and incubated overnight in an atmosphere containing 5% CO2. Culture medium is completely removed from each well and replaced with medium containing a range of drug concentrations. In the case of menadione alone, the duration of drug exposure is 1 hour, after which the cells are washed twice with Hanks' balanced salt solution prior to the addition of 200 μL fresh RPMI 1640 medium to each well of the plate. In the case of DMXAA alone, the duration of drug exposure is 3 hours. Following a four-day incubation, cell survival is determined using the MTT assay. For combinations of DMXAA with menadione, cells are initially set up and a non-toxic (>95% cell survival) concentration of DMXAA is selected. Cells are then initially exposed to DMXAA (2 mM) for a period of 2 hours, following which the medium is removed and replaced with medium containing the inhibitor (DMXAA at a constant concentration of 2 mM) and menadione (at a range of drug concentrations). Following a further 7-hour incubation, cells are washed twice with Hanks' balanced salt solution prior to the addition of growth medium.
Experimental Result Images Methods Biomarkers Images PMID
Western blot p-p38 / p38 p-MK2 / pERK / p-JNK 21819972
Growth inhibition assay Cell proliferation 30138430
In Vivo
In vivo DMXAA treatment significantly protects C57BL/6J mice infected i.n. with 200 p.f.u. mouse-adapted H1N1 influenza PR8 virus with 60% survival, while the control group only exhibited 20% survival. [2] DMXAA significantly delays tumor growth induced by chemical carcinogen, increases the time to tumor doubling and increases time from treatment to euthanasia. After the treatment of DMXAA, median tumor doubling time, median tumour tripling time and median time from treatment to euthanasia in tumor-bearing animals are increased by approximately 4.4-, 1.8- and 2.7-fold, respectively. [4]
Animal Research Animal Models Chemical carcinogen (NMU) is injected into female Wistar rats.
Dosages ≤300 mg/kg
Administration Administered via i.p.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00856336 Completed
Refractory Tumors
Antisoma Research
 May 2003 Phase 1
NCT00863733 Completed
Solid Tumors
Cancer Research UK|Cancer Society Auckland
 May 1996 Phase 1

Chemical Information & Solubility

Molecular Weight 282.29 Formula

C17H14O4
CAS No. 117570-53-3 SDF Download Vadimezan (DMXAA) SDF
Smiles CC1=C(C2=C(C=C1)C(=O)C3=CC=CC(=C3O2)CC(=O)O)C
Storage (From the date of receipt)

In vitro
Batch:

7.5%Sodium bicarbonate : 10 mg/mL (Ultrasonic and heating for 5 minutes.)

DMSO : 7 mg/mL ( (24.79 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble


Molecular Weight Calculator

In vivo
Batch:

Add solvents to the product individually and in order.


In vivo Formulation Calculator

Preparing Stock Solutions

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.

* Indicates a Required Field

Please enter your name.
Please enter your email. Please enter a valid email address.
Please write something to us.
Tags: buy Vadimezan (DMXAA) | Vadimezan (DMXAA) supplier | purchase Vadimezan (DMXAA) | Vadimezan (DMXAA) cost | Vadimezan (DMXAA) manufacturer | order Vadimezan (DMXAA) | Vadimezan (DMXAA) distributor