KU-55933
作者：齐岳
发布时间：2023-09-13
17:25:57
点击数：
产品名称：KU-55933
产品描述：
| 产品描述 | KU-55933 (ATM Kinase Inhibitor) is a potent and specific ATM inhibitor. |
| 靶点活性 | ATM:12.9 nM |
| 体外活性 | ATM抑制剂KU-55933比JAK2抑制剂AG490,或STAT3β的过表达更强烈地影响TRAIL介导的细胞凋亡.KU-55933抑制ATM依赖的STAT3激活,通过上调DR5表达增加TRAIL调节的凋亡,抑制STAT3和NF-κB都和下调cFLIP有关,伴随着凋亡水平上升. |
| 体内活性 | KU-55933是ATM有效的特定抑制剂,IC50为13 nM,Ki值为2.2 nM。KU-55933抑制ATM,通过阻断下游TAp63α的激活,提高存活力。KU-55933剂量依赖性抑制ATM依赖的磷酸化作用,IC50为300 nM。KU-55933使HeLa细胞对电离辐射敏感。KU-55933抑制癌细胞增殖。KU-55933抑制癌细胞中生长因子诱导的Akt的磷酸化作用。KU-55933也抑制DNA-PK和PI3K,IC50分别为2.5和16.6 μM。KU-55933也抑制mTOR活性,IC50为9.3 μM。小于30 μM时,KU-58050不能抑制p53的ATM-依赖性磷酸化作用（位点为第15位丝氨酸）。KU-55933的添加对UV-诱导的H2AX（位点为第139位丝氨酸）,NBS1（位点为第343为丝氨酸）,CHK1（位点为第345位丝氨酸）及SMC1（位点为第966位丝氨酸）没有明显作用效果。 |
| 激酶实验 | Purified enzyme assays: ATM for use in the in vitro assay is obtained from HeLa nuclear extract by immunoprecipitation with rabbit polyclonal antiserum raised to the COOH-terminal 400 amino acids of ATM in buffer containing 25 mM HEPES (pH 7.4), 2 mM MgCl2, 250 mM KCl, 500 μM EDTA, 100 μM Na3VO4, 10% v/v glycerol, and 0.1% v/v Igepal. ATM-antibody complexes are isolated from nuclear extract by incubating with protein A-Sepharose beads for 1 hour and then through centrifugation to recover the beads. In the well of a 96-well plate, ATM-containing Sepharose beads are incubated with 1 μg of substrate glutathione S-transferase–p53N66 (NH2-terminal 66 amino acids of p53 fused to glutathione S-transferase) in ATM assay buffer [25 mM HEPES (pH 7.4), 75 mM NaCl, 3 mM MgCl2, 2 mM MnCl2, 50 μM Na3VO4, 500 μM DTT, and 5% v/v glycerol] at 37 °C in the presence or absence of inhibitor. After 10 minutes with gentle shaking, ATP is added to a final concentration of 50 μM and the reaction continued at 37 °C for an additional 1 hour. The plate is centrifuged at 250 × g for 10 minutes (4 °C) to remove the ATM-containing beads, and the supernatant is removed and transferred to a white opaque 96-well plate and incubated at room temperature for 1.5 hours to allow glutathione S-transferase-p53N66 binding. This plate is then washed with PBS, blotted dry, and analyzed by a standard ELISA technique with a phospho-serine 15 p53 antibody. The detection of phosphorylated glutathione S-transferase-p53N66 substrate is performed in combination with a goat antimouse horseradish peroxidase-conjugated secondary antibody. Enhanced chemiluminescence solution is used to produce a signal and chemiluminescent detection is carried out. |
| 细胞实验 | U2OS cells are exposed to ionizing radiation (3, 5, or 15 Gy) or UV (5 or 50 J/m2) and the ATM response determined by Western blot analysis of p53 serine 15 phosphorylation and stabilization of wild-type p53. Whole cell extracts are obtained from each time point, proteins separated by SDS-PAGE, and the ATM-specific increase in phosphorylated serine 15 measured with a p53 phospho-serine 15 specific antibody. Overall p53 stabilization with time is also observed with a p53-specific antibody (DO-1). Similarly, for studying ATM-dependent phosphorylations on H2AX, CHK1, NBS1, and SMC1, the following antibodies are used: CHK1 phospho-serine 345 and NBS1 phospho-serine 343 antibodies. Histone H2A (H-124) and CHK1 antibodies are also used, as well as SMC1 and SMC1 phospho-serine 966 antibodies. For determination of a cellular IC50 for KU-55933, the peak response time for p53 serine 15 phosphorylation of 2 hours is used to monitor inhibition of ATM. KU-55933 is titrated onto cells and preincubated for 1 hour before ionizing radiation. Using scanning densitometry, the percentage inhibition relative to vehicle control is calculated, and the IC50 value is calculated as for the in vitro determinations.(Only for Reference) |
| 别名 | ATM Kinase Inhibitor |
| 分子量 | 395.49 |
| 分子式 | C21H17NO3S2 |
| CAS No. | 587871-26-9 |
存储
Powder: -20°C for 3 years | In solvent: -80°C for 2 years
溶解度
Ethanol: 19.8 mg/mL (50 mM)
DMSO: 39.6 mg/mL (100 mM)
( < 1 mg/mL refers to the product slightly soluble or insoluble )
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