DMXAA (Vadimezan)

Catalog No.S1537

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, respectively. Phase 3.

Price Stock Quantity  
In DMSO USD 140 In stock
USD 120 In stock
USD 370 In stock
USD 970 In stock
Bulk Inquiry

Massive Discount Available

Free Overnight Delivery on all orders over $ 500.

DMXAA (Vadimezan) Chemical Structure

DMXAA (Vadimezan) Chemical Structure
Molecular Weight: 282.29

Validation & Quality Control

Quality Control & MSDS

Related Compound Libraries

DMXAA (Vadimezan) is available in the following compound libraries:

Product Information

  • Compare VDA Chemicals
    Compare VDA Products
  • Research Area

Product Description

Biological Activity

Description 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, respectively. Phase 3.
Targets DT-diaphorase [1] DT-diaphorase [1]
IC50 20 μM(Ki) 62.5 μM
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]
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]
Features

Protocol(Only for Reference)

Kinase Assay: [1]

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 Assay: [1]

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.

Animal Study: [4]

Animal Models Chemical carcinogen (NMU) is injected into female Wistar rats.
Formulation DMXAA is dissolved in 5% sodium bicarbonate.
Dosages ≤300 mg/kg
Administration Administered via i.p.
Solubility 30% PEG400/0.5% Tween80/5% propylene glycol, 30 mg/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.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesBaboonDogMonkeyRabbitGuinea pigRatHamsterMouse
Weight (kg)121031.80.40.150.080.02
Body Surface Area (m2)0.60.50.240.150.050.0250.020.007
Km factor202012128653
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Phillips RM. Biochem Pharmacol. 1999, 58(2), 303-310.

[2] Shirey KA, et al. J Leukoc Biol. 2011, 89(3), 351-357.

view more

Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2014-12-20)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT01278758 Terminated Metastatic Cancer Novartis Pharmaceuticals|Novartis March 2010 Phase 1
NCT01278758 Terminated Metastatic Cancer Novartis Pharmaceuticals|Novartis March 2010 Phase 1
NCT01290380 Terminated Solid Tumor Malignancies Novartis Pharmaceuticals|Novartis February 2010 Phase 1
NCT01290380 Terminated Solid Tumor Malignancies Novartis Pharmaceuticals|Novartis February 2010 Phase 1
NCT01057342 Completed Lung Cancer Swiss Group for Clinical Cancer Research January 2010 Phase 2

view more

Chemical Information

Download DMXAA (Vadimezan) SDF
Molecular Weight (MW) 282.29
Formula

C17H14O4

CAS No. 117570-53-3
Storage 3 years -20℃Powder
6 months-80℃in solvent (DMSO, water, etc.)
Synonyms NSC 640488, ASA-404
Solubility (25°C) * In vitro DMSO 7 mg/mL (24.79 mM)
Water <1 mg/mL (<1 mM)
Ethanol <1 mg/mL (<1 mM)
In vivo 30% PEG400/0.5% Tween80/5% propylene glycol 30 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* 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 Name 2-(5,6-dimethyl-9-oxo-9H-xanthen-4-yl)acetic acid

Research Area

Tech Support & FAQs

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.

Tel: +1-832-582-8158 Ext:2

If you have any other enquiries, please leave a message.

* Indicates a Required Field

Related VDA Products

  • BAY 87-2243

    BAY 87-2243 is a potent and selective hypoxia-inducible factor-1 (HIF-1) inhibitor. Phase 1.

  • Entospletinib (GS-9973)

    Entospletinib (GS-9973) is an orally bioavailable, selective Syk inhibitor with IC50 of 7.7 nM. Phase 2.

  • WH-4-023

    WH-4-023 is a potent and orally active Lck/Src inhibitor with IC50 of 2 nM and 6 nM, respectively.

  • Plinabulin (NPI-2358)

    Plinabulin (NPI-2358) is a vascular disrupting agent (VDA) against tubulin-depolymerizing with IC50 of 9.8~18 nM in tumor cells. Phase 1/2.

    Features:Synthetic analog of NPI-2350 and greater potentcy than NPI-2350.

  • Ibrutinib (PCI-32765)

    Ibrutinib is a potent and highly selective Brutons tyrosine kinase (Btk) inhibitor with IC50 of 0.5 nM, modestly potent to Bmx, CSK, FGR, BRK, HCK, less potent to EGFR, Yes, ErbB2, JAK3, etc.

  • Dasatinib

    Dasatinib is a novel, potent and multi-targeted inhibitor that targets Abl, Src and c-Kit, with IC50 of <1 nM, 0.8 nM and 79 nM, respectively.

  • BGJ398 (NVP-BGJ398)

    BGJ398 (NVP-BGJ398) is a potent and selective FGFR inhibitor for FGFR1/2/3 with IC50 of 0.9 nM/1.4 nM/1 nM, >40-fold selective for FGFR versus FGFR4 and VEGFR2, and little activity to Abl, Fyn, Kit, Lck, Lyn and Yes. Phase 2.

  • Saracatinib (AZD0530)

    Saracatinib (AZD0530) is a potent Src inhibitor with IC50 of 2.7 nM, and potent to c-Yes, Fyn, Lyn, Blk, Fgr and Lck; less active for Abl and EGFR (L858R and L861Q). Phase 2/3.

    Features:The 1st Src inhibitor to show inhibition of the Src pathway in human tumor tissue.

  • Ponatinib (AP24534)

    Ponatinib (AP24534) is a novel, potent multi-target inhibitor of Abl, PDGFRα, VEGFR2, FGFR1 and Src with IC50 of 0.37 nM, 1.1 nM, 1.5 nM, 2.2 nM and 5.4 nM, respectively.

  • Imatinib Mesylate (STI571)

    Imatinib Mesylate (STI571) is an orally bioavailability mesylate salt of Imatinib, which is a multi-target inhibitor of v-Abl, c-Kit and PDGFR with IC50 of 0.6 μM, 0.1 μM and 0.1 μM, respectively.

Recently Viewed Items

Tags: buy DMXAA (Vadimezan) | DMXAA (Vadimezan) supplier | purchase DMXAA (Vadimezan) | DMXAA (Vadimezan) cost | DMXAA (Vadimezan) manufacturer | order DMXAA (Vadimezan) | DMXAA (Vadimezan) distributor
Contact Us