DMXAA (Vadimezan) 化学構造
分子量: 282.29

高品質保証

Quality Control & MSDS

製品説明

  • Compare VDA Inhibitors
    VDA製品生物活性の比較
  • 研究分野

製品の説明

生物活性

製品説明 DMXAA (Vadimezan)は、DT-ジアホラーゼ(NAD(P)H:キノン酸化還元酵素EC 1.6.99.2)の競争的阻害剤で、Ki が20 μM 、IC50が62.5 μMです。
ターゲット DT-diaphorase DT-diaphorase
IC50 62.5 μM 20 μM (Ki) [1]
In vitro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]
In vivo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]
臨床試験 DMXAA is currently in Phase II clinical trials in patients with non-small cell lung cancer.
特集

プロトコル (参考用のみ)

キナーゼアッセイ: [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

細胞アッセイ: [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.

動物実験: [4]

動物モデル Chemical carcinogen (NMU) is injected into female Wistar rats.
製剤 DMXAA is dissolved in 5% sodium bicarbonate.
投薬量 ≤300 mg/kg
投与方法 Administered via i.p.

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

SpeciesMouseRatRabbitGuinea pigHamsterDogMonkeyBaboon
Weight (kg)0.020.151.80.40.0810312
Body Surface Area (m2)0.0070.0250.150.050.020.50.240.6
Km factor361285201220
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

参考

化学情報

Download DMXAA (Vadimezan) SDF
分子量 282.29
化学式

C17H14O4

CAS No. 117570-53-3
保管 2年-20℃
6月-80℃in solvent
別名 NSC 640488, ASA-404
溶解度 (25°C) * In vitro DMSO 7 mg/mL (24.79 mM)
<1 mg/mL (<1 mM)
エタノール <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.
化学名 2-(5,6-dimethyl-9-oxo-9H-xanthen-4-yl)acetic acid

技術サポート&よくある質問(FAQ)

ストックの作り方、阻害剤の保管する方法、細胞実験や動物実験に注意すべきな点を全部含めており、製品を取扱う時よくあった質問に対して取扱説明書でお答えいたします。

電話番号: +1-832-582-8158 Ext:3月曜日〜金曜日 9:00 AM–5:00 PM (米国中部標準時)

他の質問がある場合は、お気軽くお問合せください。

* 必須

Related VDA 阻害剤

  • BAY 87-2243

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

  • PX-478 2HCl

    PX-478 2HCl is an orally active, and selective hypoxia-inducible factor-1α (HIF-1α) inhibitor. Phase 1.

  • Defactinib (VS-6063, PF-04554878)

    Defactinib (VS-6063, PF-04554878) is a selective, and orally active FAK inhibitor. Phase 2.

  • WH-4-023

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

  • Plinabulin (NPI-2358)

    Plinabulin (NPI-2358)はチュービュリンを解重合しているエージェントで、9.8~18nMのIC50で、腫瘍細胞を妨げます。

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

  • Verteporfin

    Verteporfin(Visudyne), a benzoporphyrin derivative, is a medication used as a photosensitizer for photodynamic therapy.

  • Ibrutinib (PCI-32765)

    Ibrutinib (PCI-32765)は、0.5nMのIC50による有力で非常に選択的なブラットンのチロシン・キナーゼ(Btk)阻害剤です。

  • Dasatinib

    Dasatinib は、野生型ablとSrcのためのSrc/abl阻害剤で、IC50 がそれぞれ 0.6 nM と 0.8 nMです。

  • Saracatinib (AZD0530)

    Saracatinib(AZD0530)は、c-SrcのためのSrc阻害剤で、IC50 が2.7 nMです。

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

最近チェックしたアイテム

Tags: DMXAA (Vadimezan)を買う | DMXAA (Vadimezan)供給者 | DMXAA (Vadimezan)を購入する | DMXAA (Vadimezan)費用 | DMXAA (Vadimezan)生産者 | オーダーDMXAA (Vadimezan) | DMXAA (Vadimezan)代理店
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description
お問い合わせ