| 名稱 | Vadimezan |
| 描述 | Vadimezan (DMXAA) is a vascular disrupting agent, a murine STING agonist, and an inducer of cytokines such as type I IFN. Vadimezan has antitumor activity and induces a rapid cessation of blood flow in tumors without affecting blood flow in normal tissues. |
| 細(xì)胞實(shí)驗(yàn) | 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) |
| 激酶實(shí)驗(yàn) | 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 |
| 體外活性 | 方法：DLBCL 細(xì)胞 LY1 和 LY3 用 Vadimezan (0-300 μM) 處理 24 h，使用 CCK-8 assay 檢測細(xì)胞活力。
結(jié)果：Vadimezan 處理以劑量依賴的方式降低 DLBCL 細(xì)胞的活力，對 LY1 和 LY3 的 IC50 分別為 177 μM 和 165 μM。[1]
方法：人肺癌細(xì)胞 A549 用 Vadimezan (0.1-1 μM) 處理 24 h，使用 Western Blot 檢測靶點(diǎn)蛋白表達(dá)水平。
結(jié)果：Vadimezan 誘導(dǎo) cytochrome c 的胞漿水平和 caspase 3 的激活顯著增加，最終導(dǎo)致 A549 細(xì)胞凋亡死亡。[2] |
| 體內(nèi)活性 | 方法：為檢測體內(nèi)抗腫瘤活性，將 Vadimezan (20 mg/kg) 和 BMS1166 (250 μg/mL) 腹腔注射給攜帶 DLBCL 腫瘤 LY1 的 Balb/c nude 小鼠，每天一次，持續(xù)八天。
結(jié)果：Vadimezan 和 BMS1166 在有效濃度下發(fā)揮作用。與單藥治療相比，聯(lián)合治療顯著抑制了 GCB 樣 DLBCL 細(xì)胞的生長。[1]
方法：為檢測體內(nèi)抗腫瘤活性，將 Vadimezan (25,5,5,25 mg/kg；25,0,0,25 mg/kg；25,25,25,25 mg/kg) 腹腔注射攜帶小鼠間皮瘤 AE17 的 C57BL/6J 小鼠，每三天一次，給藥四次。
結(jié)果：在第 1 組中，治愈了 2/4 只小鼠，其中 2/4 只顯示出長期存活，但觀察到了毒性問題。在第 2 組中觀察到更好、毒性更小的反應(yīng)，所有 4 只小鼠均治愈并顯示出長期存活。在第 3 組小鼠中，只有 1 只治愈，但沒有一只長期存活，可能是由于相關(guān)的毒性問題。[3] |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 7.5 mg/mL (26.57 mM), Sonication is recommended.
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 0.57 mg/mL (2.02 mM), Suspension. Working solution is recommended to be prepared and used immediately.
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| 關(guān)鍵字 | Interferon-α/β receptor | Stimulator of Interferon Genes | Vadimezan | Influenza Virus | MITA | TMEM173 | IFNAR | inhibit | Inhibitor | STING | NSC-640488 | MPYS | ERIS | ASA 404 | ASA404 | NSC640488 | Interferon-alpha/beta receptor |
| 相關(guān)產(chǎn)品 | Crystal Violet | N-Acetylneuraminic acid | Salcomine | β-Cyclodextrin | Nitazoxanide | Curcumin | α-Vitamin E | Acetylcysteine | Naringenin | Rifampicin |
| 相關(guān)庫 | 抗癌活性化合物庫 | 經(jīng)典已知活性庫 | 已知活性化合物庫 | 抗病毒庫 | 抗肺癌化合物庫 | 藥物功能重定位化合物庫 | 抗癌臨床化合物庫 | 表型篩選靶點(diǎn)鑒定庫 | 抗癌藥物庫 | 抗前列腺癌化合物庫 |