DMXAA (Vadimezan)

Name: DMXAA (Vadimezan)
Brand: Selleck Chemicals
SKU: S1537
Rating: 5 (8 reviews)

For research use only.

Catalog No.S1537 Synonyms: NSC 640488, ASA-404

8 publications

Molecular Weight(MW): 282.29

DMXAA (Vadimezan) 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.

Selleck's DMXAA (Vadimezan) has been cited by 8 publications

Cancer Discov, 2019, 9(6):722-737

PubMed: 31015319 ( click the link to review the publication )

Immunity, 2020, 7 pii: S1074-7613(20)30129-1

PubMed: 32277911 ( click the link to review the publication )

ChemMedChem, 2018, 13(19):2057-2064

PubMed: 30079976 ( click the link to review the publication )

PLoS One, 2018, 13(8):e0202827

PubMed: 30138430 ( click the link to review the publication )

Neuron, 2017, 96(6):1290-1302

PubMed: 29268096 ( click the link to review the publication )

J Exp Med, 2017, 214(6):1769-1785

PubMed: 28484079 ( click the link to review the publication )

J Immunol, 2016, 196(7):3191-8

PubMed: 26927800 ( click the link to review the publication )

J Immunol, 2015, 194(9):4477-88

PubMed: 25810395 ( click the link to review the publication )

5 Customer Reviews

(B and C) sh-scrambled or sh-ck2a–transducted L929 cells (B) and Raw cells (C) were stimulated by DMXAA (100 μg/ml) for various times. Cytosolic and nuclear extracts were prepared as described in Materials and Methods. Five percent of the cytosolic proteins and 20% of the nuclear proteins were resolved by 10% SDS-PAGE. Subsequently, immunoblotting was conducted by indicated Abs. The amounts of Tubulin and Lamin B1 in cytosol versus nuclei detected by respective Abs were used as internal control for fractionation.

J Immunol, 2015, 194:4477-4488. DMXAA (Vadimezan) purchased from Selleck.

(E) WT and ASC−/− macrophages were stimulated with 1 μg/ml of tumor-derived DNA in the presence of lipofectamine or 50 μg/ml of DMXAA at different time points. Whole cell extracts were analysed with antibodies against pTBK1, total TBK1, pIRF3, total IRF3 and GAPDH.

J Immunol, 2016, 196(7):3191-8. DMXAA (Vadimezan) purchased from Selleck.
(B and C) sh-scrambled or sh-ck2α–transducted L929 cells (B) and Raw cells (C) were stimulated by DMXAA (100 μg/ml) for various times. Cytosolic and nuclear extracts were prepared as described in Materials and Methods. Five percent of the cytosolic proteins and 20% of the nuclear proteins were resolved by 10% SDS-PAGE. Subsequently, immunoblotting was conducted by indicated Abs. The amounts of Tubulin and Lamin B1 in cytosol versus nuclei detected by respective Abs were used as internal control for fractionation.

J Immunol, 2015, 194(9):4477-88. DMXAA (Vadimezan) purchased from Selleck.

(b-e) HEK293T cells were transiently transfected with empty vector (b), plasmids encoding hSTING(H232) (c), hSTING(R232) (d), or mSTING (e) together with IFNβ-luciferase reporter. After 24 h, cells were transfected with 2′,3′‐cGAMP (2 μg/mL) or stimulated with CMA (50 μg/mL), DMXAA (50 μM) and α-mangostin. Luciferase activity was measured 24 h after stimulation. Error bars represent the SD of independent experiments (n=3); *P<0.05, **P<0.01, ***P<0.001 (Student's t-test).

ChemMedChem, 2018, 13(19):2057-2064. DMXAA (Vadimezan) purchased from Selleck.
(A) 24 h after incubation of co-culture of B16.F10 cells and TAMs with different concentrations of DMXAA; (B) 24 h after incubation of co-culture of B16.F10 cells and TAMs with different concentrations of SIM administered alone or in combination with 100 μM DMXAA; (C) 24 h after incubation of mono-cultured B16.F10 cells with 100 μM DMXAA administered alone and with different concentrations of SIM administered alone or in combination with 100 μM DMXAA. Data are shown as mean ± SD of triplicate measurements; DMXAA: cells incubated with different concentrations of DMXAA; SIM: cells incubated with different concentrations of SIM; SIM+ 100 μM DMXAA: cells incubated with different concentrations of SIM administered in combination with 100 μM DMXAA; The two-way ANOVA Multiple Comparison Test with Bonferroni post-tests was used to compare overall effects of different drug concentrations (*, P<0.05; **, P<0.01; ***, P<0.001).

PLoS One, 2018, 13(8):e0202827. DMXAA (Vadimezan) purchased from Selleck.

Purity & Quality Control

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Biological Activity

Description

Targets

DT-diaphorase ^[1] (Cell-free assay)	DT-diaphorase ^[1] (Cell-free assay)
20 μM(Ki)	20 μM(Ki)

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]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID
human BJ cells	MofrR5l1d3SxeHnjxsBie3OjeR?=		M37EfFI1KGh?		NYrKU2tOS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hSkpiY3XscJMh[W[2ZYKgNlQhcHK\|IHL5JG1VXCCjc4PhfUwhS0N3ME20PE46KM7:TR?=	M3n2flI1PTF6Mkm1
HECPP cells	MlnwSpVv[3Srb36gZZN{[Xl?	NV3vbJNoOTBidXevcWw>			NX30UmJpSWO2aY\heIlwdiCxZjDOSk1s[XCyYVKgbY4hUEWFUGCgZ4VtdHNiYYSgNVAhfWdxbVy=	MVuxO\|YyPjFzNB?=

... Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID
Western blot	p-p38 / p38 ; PubMed: 21819972 Biochem Pharmacol Mouse macrophages (MHS) were stimulated with 20 µg/ml DMXAA in culture. At various time points, the culture supernatants and the cells were collected and assayed for amount of p38 phosphorylation with immunoblots. p-MK2 / pERK / p-JNK ; PubMed: 21819972 Biochem Pharmacol Mouse macrophages (MHS) were pre-exposed to IFN-γ, followed by DMXAA treatment at 20 µg/ml. The cells also extracted to determine the effect of IFN-γ priming on DMXAA-induced MAPK pathways activation.	21819972
Growth inhibition assay	Cell proliferation ; PubMed: 30138430 PLoS One 24 h after incubation of co-culture of B16.F10 cells and TAMs with different concentrations of DMXAA;	30138430

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]

Protocol

Kinase Assay:^[1]	- Collapse 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. K_i 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:^[1]	- Collapse 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. (Only for Reference)
Animal Research:^[4]	- Collapse Animal Models: Chemical carcinogen (NMU) is injected into female Wistar rats. Dosages: ≤300 mg/kg Administration: Administered via i.p. (Only for Reference)

References

[4] Liu JJ, et al. Cancer Chemother Pharmacol. 2007, 59(5), 661-669.

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Solubility (25°C)

In vitro	DMSO	7 mg/mL (24.79 mM)
	Water	Insoluble
	Ethanol	Insoluble
In vivo	Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 5% NaHCO3 (aq) warmed For best results, use promptly after mixing.	30mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information Download DMXAA (Vadimezan) SDF

Molecular Weight	282.29
Formula	C₁₇H₁₄O₄
CAS No.	117570-53-3
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	NSC 640488, ASA-404
Smiles	CC1=C(C)C2=C(C=C1)C(=O)C3=C(O2)C(=CC=C3)CC(O)=O

In vivo Formulation Calculator (Clear solution)

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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 DMSO master liquid, next addμL PEG300， mix and clarify, next addμL Tween 80，mix and clarify, next add μL ddH₂O，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.

Bio Calculators

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This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

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The Serial Dilution Calculator Equation

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Molecular Weight Calculator

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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

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DMXAA (Vadimezan)