Powder: -20°C for 3 years | In solvent: -80°C for 2 years
Nutlin3 是一种 MDM2 拮抗剂,抑制 MDM2-p53 相互作用 ,Ki 为 90 nM,并激活 p53。
产品描述 | Nutlin-3 is an MDM2 antagonist. Nutlin-3 inhibits the MDM2-p53 interaction (IC50: 0.09 μM) and activates p53. Antiproliferative agent; chemotherapeutic agent; induces apoptosis in Y cells. |
靶点活性 | MDM2-p53:0.09 μM |
体外活性 | Nutlin-3 is an inhibitor of the MDM2-p53 interaction. In particular, co-treatment of p53-positive HCT116 cells with 1 μM of Inauhzin and 2 μM of Nutlin-3 more significantly activated p53 as measured by its protein level as well as the level of its target p21, PUMA or cleaved PARP as indication of apoptosis[2]. Nutlin-3 is a small-molecule inhibitor that acts to inhibit MDM2 binding to p53 and subsequent p53-dependent DNA damage signaling. Nutlin-3 (2-10 μM) stabilizes p53 and p21WAF levels and is toxic to WTp53-22RV1 cells (IC50, 4.3 μM) as a single agent, but has minimal toxicity toward p53-deficient cells (IC50, >10 μM). Nutlin-3 induces p53 and p21WAF expression in a dose-dependent manner in 22RV1 cells. Short-term cell cycle assays show that, at a dose of 10 μM, Nutlin-3 increasea slightly the G1-phase fraction and decreasea S-phase fraction of all three cell lines[3]. |
体内活性 | Nutlin-3 is able to suppress the growth of xenograft tumors derived from human osteosarcoma or leukemia cells, the anti-tumor activity of Nutlin-3 even at the dose of 200 mg/kg per oral administration is marginal in an HCT116-derived xenograft tumor model[2]. Nutlin-3 may be a useful adjunct to improve the therapeutic ratio using precision radiotherapy targeted to hypoxic cells and warrants further study in vivo[3]. |
激酶实验 | Biacore study: Competition assay is performed on a Biacore S51. A Series S Sensor chip CM5 is utilized for the immobilization of a PentaHis antibody for capture of the His-tagged p53. The level of capture is ~200 response units (1 response unit corresponds to 1 pg of protein per mm 2). The concentration of MDM2 protein is kept constant at 300 nM. Nutlin-3 is dissolved in DMSO at 10 mM and further diluted to make a concentration series of Nutlin-3 in each MDM2 test sample. The assay is run at 25°C in running buffer (10 mM Hepes, 0.15 M NaCl, 2% DMSO). MDM2-p53 binding in the presence of Nutlin-3 is calculated as a percentage of binding in the absence of Nutlin-3 and IC50 is calculated |
细胞实验 | Nutlin-3 (NUT) is dissolved with DMSO (100 mM) and diluted with appropriate media[2]. Human non-small-cell lung carcinoma wild type p53-containing H460 and A549, human non-small-cell lung carcinoma p53-null H1299, and human colon cancer HCT116 (p53+/+ and p53-/-) cells are used. Cells (1.5×105) are plated into 6-well plates, and incubated at 37°C overnight. After treatment of Inauhzin and Nutlin-3 at the indicated concentrations for 48 h, cells are harvested, fixed in 70% ice-cold ethanol overnight at -20°C, resuspended in propidium iodide-solution (50 μg/mL PI, 0.1 mg/mL RNase A, 0.05% Tritin X-100 in PBS) for 40 min at 37°C, then analyzed for DNA content using a flow cytometer and proprietary software[2]. |
别名 | Nutlin3 |
分子量 | 581.49 |
分子式 | C30H30Cl2N4O4 |
CAS No. | 548472-68-0 |
Powder: -20°C for 3 years | In solvent: -80°C for 2 years
DMSO: 55 mg/mL (94.58 mM)
( < 1 mg/mL refers to the product slightly soluble or insoluble )
对于不同动物的给药剂量换算,您也可以参考 更多...
请在以下方框中输入您的动物实验信息后点击计算,可以得到母液配置方法和体内配方的制备方法: 比如您的给药剂量是10 mg/kg,每只动物体重20 g,给药体积100 μL,一共给药动物10 只,您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。
母液配置方法:2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL), 如您需要配置的浓度超过该产品的溶解度,请先与我们联系。
体内配方的制备方法:取 50 μL DMSO 主液,加入 300 μL PEG300, 混匀澄清,再加 50 μL Tween 80,混匀澄清,再加 600 μL ddH2O, 混匀澄清。
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您可能有的问题的答案可以在抑制剂处理说明中找到,包括如何准备库存溶液,如何存储产品,以及基于细胞的分析和动物实验需要特别注意的问题。
Nutlin-3 548472-68-0 Ubiquitination E1/E2/E3 Enzyme E3 ligating enzyme E2 conjugating enzyme E1 activating enzyme Ubiquitin conjugating enzyme inhibit MDM-2/p53 Nutlin 3 Ubiquitin activating enzyme Inhibitor Ubiquitin ligase Nutlin3 inhibitor