Vadimezan (ASA404)

製品コード:S1537 別名:NSC 640488, DMXAA

For research use only.

Vadimezan (ASA404, NSC 640488, 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 (ASA404)化学構造

CAS No. 117570-53-3

サイズ 価格(税別)
10mM (1mL in DMSO) JPY 25200
JPY 21900
JPY 63400
JPY 163000

代表番号: 03-5615-9297|電子メール:[email protected]
よく尋ねられる質問

文献中Selleckの製品使用例(24)

製品安全説明書

VDA阻害剤の選択性比較

相関VDA製品

生物活性

製品説明 Vadimezan (ASA404, NSC 640488, 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.
ターゲット
DT-diaphorase [1]
(Cell-free assay)
DT-diaphorase [1]
(Cell-free assay)
20 μM(Ki) 20 μM(Ki)
体外試験

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]

細胞データ
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human BJ cells MkDaR5l1d3SxeHnjxsBie3OjeR?= M2PHeVI1KGh? NWfFSG9HS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hSkpiY3XscJMh[W[2ZYKgNlQhcHK|IHL5JG1VXCCjc4PhfUwhS0N3ME20PE46KM7:TR?= NYnZVJhIRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS1NVgzQTVpPkK0OVE5Ojl3PD;hQi=>
HECPP cells M2fYWWZ2dmO2aX;uJIF{e2G7 NVPzR5N[OTBidXevcWw> M1K3T2FkfGm4YYTpc44hd2ZiTl[tb4FxeGGEIHnuJGhGS1CSIHPlcIx{KGG2IEGwJJVoN22O NWTZcoZyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUe2NVYyOTRpPkG3OlE3OTF2PD;hQi=>
MCF7 MojERY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl? NFzoRpQzPCCqcoO= NXXMNolmSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDNR2Y4KGOnbHzzJINwNXS{ZXH0[YQhf2m2aDDwfZJidm:6YX70bI9v\SCjdDCxPlEhdW:uYYKgdoF1cW9iYX\0[ZIhOjRiaILzJIJ6KE2WVDDhd5NigSxiSVO1NEA:KDFzLki5JO69VS5? MW[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTF{OUWxNUc,OjlzMkm1NVE9N2F-
MDA-MB-231 M{\idGFvfGmycn;sbYZmemG2aY\lJIF{e2G7 M{G0WVI1KGi{cx?= NEHXSWFCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIF3ERU1OSi1{M{GgZ4VtdHNiY3:teJJm[XSnZDD3bZRpKHC7cnHuc5hidnSqb37lJIF1KDF8MTDtc4xieiC{YYTpc{Bi\nSncjCyOEBpenNiYomgUXRVKGG|c3H5MEBKSzVyIE2gNVIvOTJizszNMi=> Mn\qQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjlzMkm1NVEoRjJ7MUK5OVEyRC:jPh?=
K562 NWnM[oluSW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= Ml3nNlQhcHK| MlXsRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCNNU[yJINmdGy|IHPvMZRz\WG2ZXSge4l1cCCyeYLhco95[W62aH;u[UBifCBzOkGgcY9t[XJicnH0bY8h[W[2ZYKgNlQhcHK|IHL5JG1VXCCjc4PhfUwhUUN3MDC9JFE6NjF2IN88UU4> NUOwVmNVRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkmxNlk2OTFpPkK5NVI6PTFzPD;hQi=>
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HepG2 NV7uNIV[SXCxcITvd4l{KGG|c3H5 M{Xlc|AvOiC3TR?= MVqyOEBpenN? MYfJcoR2[3Srb36gc4Yh[XCxcITvd4l{KGmwIHj1cYFvKEincFeyJINmdGy|IHHzd4V{e2WmIHHzJIlv[3KnYYPlJIlvKGOuZXH2[YQh[2G|cHHz[U06KGyndnXsd{BifCByLkKgeW0h[W[2ZYKgNlQhcHK|IHL5JHdme3Sncn6gZoxwfCCvZYToc4Q> NIjWVYg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUGyPVUyOSd-MkmxNlk2OTF:L3G+
HepG2 NXvzWGhSSXCxcITvd4l{KGG|c3H5 M{LGeVI1KGi{cx?= M4DQXGlv\HWldHnvckBw\iCjcH;weI9{cXNiaX6gbJVu[W5iSHXwS|Ih[2WubIOgZZN{\XO|ZXSgZZMhcW6lcnXhd4UhcW5iY3zlZZZm\CCSQWLQJIxmfmWuczDjc{11emWjdHXkJJdqfGhicInyZY5wgGGwdHjvcoUh[XRiMUqxJI1wdGG{IILheIlwKGGodHXyJFI1KGi{czDifUBY\XO2ZYLuJIJtd3RibXX0bI9l MVG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTF{OUWxNUc,OjlzMkm1NVE9N2F-
HepG2 M3fFVWFxd3C2b4Ppd{Bie3OjeR?= NV[x[llEOC5{IIXN NXL6fIhNOjRiaILz MkL5TY5lfWO2aX;uJI9nKGGyb4D0c5NqeyCrbjDoeY1idiCKZYDHNkBk\WyuczDhd5Nme3OnZDDhd{BqdmO{ZXHz[UBqdiClbHXheoVlKFCDUmCgcIV3\Wy|IHH0JFAvOiC3TTDh[pRmeiB{NDDodpMh[nliV3XzeIVzdiCkbH;0JI1mfGixZB?= M4jVWFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7MUK5OVEyLz5{OUGyPVUyOTxxYU6=
HepG2 NFvZeIpCeG:ydH;zbZMh[XO|YYm= NGXjeHUzPCCqcoO= MYrJcoR2[3Srb36gc4Yh[XCxcITvd4l{KGmwIHj1cYFvKEincFeyJINmdGy|IHHzd4V{e2WmIHHzJIlv[3KnYYPlJIlvKGOuZXH2[YQh[2G|cHHz[U0{KGyndnXsd{Bkdy22cnXheIVlKHerdHigdJlz[W6xeHHueIhwdmViYYSgNVoyKG2xbHHyJJJifGmxIHHmeIVzKDJ2IHjyd{BjgSCZZYP0[ZJvKGKub4SgcYV1cG:m NYH2R4ZHRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkmxNlk2OTFpPkK5NVI6PTFzPD;hQi=>
HepG2 NWnHU4drSXCxcITvd4l{KGG|c3H5 MXGyOEBpenN? NE\XT3pKdmS3Y4Tpc44hd2ZiYYDvdJRwe2m|IHnuJIh2dWGwIFjldGczKGOnbHzzJIF{e2W|c3XkJIF{KGmwY4LlZZNmKGmwIHPs[YF3\WRiY3HzdIF{\S17IHzleoVteyClbz30doVifGWmIIfpeIgheHm{YX7vfIFvfGixbnWgZZQhOTpzIH3vcIFzKHKjdHnvJIFnfGW{IEK0JIhzeyCkeTDX[ZN1\XKwIHLsc5QhdWW2aH;k NH3U[Hc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUGyPVUyOSd-MkmxNlk2OTF:L3G+
HepG2 NYW5bpBMSXCxcITvd4l{KGG|c3H5 MU[yOEBpenN? NWH4NHNTUW6mdXP0bY9vKG:oIHHwc5B1d3OrczDpckBpfW2jbjDI[ZBIOiClZXzsd{Bie3Onc4Pl[EBieyCmb4fudoVofWyjdHnvckBw\iCEY3ytfGwh\XiycnXzd4lwdiClbz30doVifGWmIIfpeIgheHm{YX7vfIFvfGixbnWgZZQhOTpzIH3vcIFzKHKjdHnvJIFnfGW{IEK0JIhzeyCkeTDX[ZN1\XKwIHLsc5QhdWW2aH;k MUW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTF{OUWxNUc,OjlzMkm1NVE9N2F-
HepG2 M1\3bGFxd3C2b4Ppd{Bie3OjeR?= NXzxUIRFOjRiaILz NGL6OIhKdmS3Y4Tpc44hd2ZiYYDvdJRwe2m|IHnuJIh2dWGwIFjldGczKGOnbHzzJIF{e2W|c3XkJIF{KHWycnXneYxifGmxbjDv[kBDcWRiZYjwdoV{e2mxbjDjc{11emWjdHXkJJdqfGhicInyZY5wgGGwdHjvcoUh[XRiMUqxJI1wdGG{IILheIlwKGGodHXyJFI1KGi{czDifUBY\XO2ZYLuJIJtd3RibXX0bI9l MXy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTF{OUWxNUc,OjlzMkm1NVE9N2F-
アッセイ
Methods Test Index PMID
Western blot p-p38 / p38 ; p-MK2 / pERK / p-JNK 21819972
Growth inhibition assay Cell proliferation 30138430
体内試験 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]

お薦めの試験操作(参考用のみ)

キナーゼ試験:[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

細胞試験:[1]
  • 細胞株:DLD-1 and H460 cells
  • 濃度: 0-2 mM
  • 反応時間:96 hours
  • 実験の流れ: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.
動物試験:[4]
  • 動物モデル:Chemical carcinogen (NMU) is injected into female Wistar rats.
  • 投薬量:≤300 mg/kg
  • 投与方法:Administered via i.p.

溶解度 (25°C)

体外

化学情報

分子量 282.29
化学式

C17H14O4

CAS No. 117570-53-3
Storage 3年 -20°C
2年 -80°C in solvent
Smiles CC1=C(C2=C(C=C1)C(=O)C3=CC=CC(=C3O2)CC(=O)O)C

投与溶液組成計算機(クリア溶液)

ステップ1:実験データを入力してください。(実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します)

mg/kg g μL

ステップ2:投与溶媒の組成を入力してください。(ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください)

% DMSO % % Tween 80 % ddH2O
%DMSO %

計算結果:

投与溶媒濃度: mg/ml;

DMSOストック溶液調製方法: mg 試薬を μL DMSOに溶解する(濃度 mg/mL, 注:濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法:Take μL DMSOストック溶液に μL PEG300,を加え、完全溶解後μL Tween 80,を加えて完全溶解させた後 μL ddH2O,を加え完全に溶解させます。

投与溶媒調製方法:μL DMSOストック溶液に μL Corn oil,を加え、完全溶解。

注意:1.ストック溶液に沈殿、混濁などがないことをご確認ください;
2.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

便利ツール

質量 濃度 体積 分子量

臨床試験

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT00856336 Completed Drug: DMXAA Refractory Tumors Antisoma Research May 2003 Phase 1
NCT00863733 Completed Drug: DMXAA Solid Tumors Cancer Research UK|Cancer Society Auckland May 1996 Phase 1

(data from https://clinicaltrials.gov, updated on 2022-08-01)

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