NU7441 (KU-57788)
(Synonyms: 8-(4-二苯并噻吩基)-2-(4-吗啉基)-4H-1-苯并吡喃-4-酮,KU 57788; NU-7441;KU57788;NU7441;NU 7441) 目录号 : GC11251
NU7441 (KU-57788)是一种高效的选择性DNA依赖性蛋白激酶（DNA-PK）抑制剂，IC50为13nM。NU7441还抑制磷脂酰肌醇3-激酶（PI3K）和哺乳动物雷帕霉素靶蛋白（mTOR），IC50分别为5.0和1.7μM。
Cas No.:503468-95-9
Sample solution is provided at 25 µL, 10mM.
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NU7441 (KU-57788) is a highly potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor with an IC50 of 13nM[1]. NU7441 also inhibits phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) with IC50 of 5.0 and 1.7μM, respectively[2]. NU7441 is an inhibitor of the non-homologous end joining (NHEJ) pathway[3].
In vitro, NU7441 (0.1-10μM) treatment of human hepatocellular carcinoma HepG2 cells for 72h dose- and time-dependently inhibited cell proliferation, reduced cellular pDNA-PKcs (S2056) protein expression, increased G2/M phase arrest of the cell cycle and induced apoptosis[4]. NU7441 (0.5-10µM) treatment of human oral squamous cell carcinoma cell lines (HSC2 and HSC2-R cells) for 0-48h significantly enhanced 6Gy X-ray irradiation-induced apoptosis and abolished colony formation in both cell lines[5].
In vivo, NU7441 (10mg/kg/day) was treated by intraperitoneal injection for 10 days in ovalbumin-induced asthmatic mice, which aggravated the degree of DNA damage in the mouse airways, but inhibited the infiltration of inflammatory cells and the level of inflammatory cytokines in the lungs[6]. NU7441 (5mg/kg) was treated by intratracheal administration in acute lung injury (ALI) mice, which significantly reduced pulmonary edema and reduced the production of inflammatory cytokines in bronchoalveolar lavage fluid (BALF)[7].
References:
[1] Hardcastle I R, Cockcroft X, Curtin N J, et al. Discovery of potent chromen-4-one inhibitors of the DNA-dependent protein kinase (DNA-PK) using a small-molecule library approach[J]. Journal of medicinal chemistry, 2005, 48(24): 7829-7846.
[2] Ma C C, Li H, Wan R Z, et al. Developments of DNA-dependent protein kinase inhibitors as anticancer agents[J]. Mini Reviews in Medicinal Chemistry, 2014, 14(11): 884-895.
[3] Iglesias-Corral D, García-Valles P, Arroyo-Garrapucho N, et al. Chloroquine-induced DNA damage synergizes with DNA repair inhibitors causing cancer cell death[J]. Frontiers in Oncology, 2024, 14.
[4] Yang C, Wang Q, Liu X, et al. NU7441 enhances the radiosensitivity of liver cancer cells[J]. Cellular Physiology and Biochemistry, 2016, 38(5): 1897-1905.
[5] Ohuchi K, Saga R, Hasegawa K, et al. DNA PKcs phosphorylation specific inhibitor, NU7441, enhances the radiosensitivity of clinically relevant radioresistant oral squamous cell carcinoma cells[J]. Biomedical Reports, 2023, 18(4): 1-8.
[6] Wang Y, Lin J, Shu J, et al. Oxidative damage and DNA damage in lungs of an ovalbumin-induced asthmatic murine model[J]. Journal of Thoracic Disease, 2018, 10(8): 4819.
[7] Pyakurel K, Ghonim M, Ibba S, et al. DNA‐Dependent Protein Kinase Inhibition Prevents Manifestation of Acute Lung Injury in Mice, a Novel Target Associated with Th1 Type Disease[J]. The FASEB Journal, 2016, 30: 1202.4-1202.4.
NU7441 (KU-57788)是一种高效的选择性DNA依赖性蛋白激酶（DNA-PK）抑制剂，IC50为13nM[1]。NU7441还抑制磷脂酰肌醇3-激酶（PI3K）和哺乳动物雷帕霉素靶蛋白（mTOR），IC50分别为5.0和1.7μM[2]。NU7441是非同源性末端接合（NHEJ）通路抑制剂[3]。
在体外，NU7441（0.1-10µM）处理人肝癌HepG2细胞72h，剂量和时间依赖性地抑制了细胞增殖，降低了细胞pDNA-PKcs（S2056）蛋白表达，增加了细胞周期的G2/M期阻滞和诱导细胞凋亡[4]。NU7441（0.5-10µM）处理人口腔鳞状细胞癌细胞系（HSC2和HSC2-R细胞） 0-48h，显著增强了6Gy X射线照射诱导的细胞凋亡，消除了两种细胞系中的集落形成[5]。
在体内，NU7441（10mg/kg/day）通过腹腔注射治疗卵清蛋白诱导的哮喘小鼠10天，加重了小鼠气道的DNA损伤程度，但抑制了肺部炎症细胞的浸润和炎症细胞因子的水平[6]。NU7441（5mg/kg）通过气管内施用治疗急性肺损伤（ALI）小鼠，显著减少了小鼠的肺水肿，减少了支气管肺泡灌洗液（BALF）中炎症细胞因子的产生[7]。
| Cell experiment [1]: | |
Cell lines | HepG2 cells |
Preparation Method | HepG2 cells (4000 per well) were cultured in a 96-well plate for 24h. Once the cells completed the attachment, 0.1, 1, 5, and 10µM of NU7441 were added to the culture media. After 12h of NU7441 treatment, 10% CCK-8 solution was added into the culture media, and the incubation continued for 2h. OD450 values were determined by a spectrometer, and the results were analyzed to measure the cell growth. |
Reaction Conditions | 0.1, 1, 5, and 10µM;12h |
Applications | NU7441 inhibits the growth of HepG2 cells in a dose- and time-dependent manner. |
| Animal experiment [2]: | |
Animal models | Female BALB/c mice |
Preparation Method | Female BALB/c mice, 6 weeks old and (18±2) g weight were divided into 4 groups equally and randomly: normal group, asthmatic group (OVA group), asthmatic mice treated with NU7441 (NU group), and asthmatic mice treated with vehicle for NU7441 (OVA+vehicle group). Mice were sensitized with 100 µL sensitization liquid [20µg ovalbumin (OVA) and 3mg Al(OH)3 emulsified in saline] per mice by intraperitoneally on days 0, 7, 14, and challenged with 1% OVA aerosol for 30min from days 21. The normal group was sensitized and challenged with saline instead of OVA. NU7441 at dose of 10mg/kg or vehicle (5% DMSO) was administered intraperitoneally once a day on days 21 to days 30, 30min after OVA challenge. |
Dosage form | 10mg/kg/day for 10 days; i. p. |
Applications | The OVA-exposed group had obvious airway inflammation characteristics, and NU7441 significantly reduced inflammatory cell infiltration and ciliary damage. In addition, NU7441 aggravated the degree of DNA damage in the airways of asthmatic mice. |
References: [1]Yang C, Wang Q, Liu X, et al. NU7441 enhances the radiosensitivity of liver cancer cells[J]. Cellular Physiology and Biochemistry, 2016, 38(5): 1897-1905. [2]Wang Y, Lin J, Shu J, et al. Oxidative damage and DNA damage in lungs of an ovalbumin-induced asthmatic murine model[J]. Journal of Thoracic Disease, 2018, 10(8): 4819. | |
| Cas No. | 503468-95-9 | SDF | |
| 别名 | 8-(4-二苯并噻吩基)-2-(4-吗啉基)-4H-1-苯并吡喃-4-酮,KU 57788; NU-7441;KU57788;NU7441;NU 7441 | ||
| 化学名 | 8-dibenzothiophen-4-yl-2-morpholin-4-ylchromen-4-one | ||
| Canonical SMILES | C1COCCN1C2=CC(=O)C3=C(O2)C(=CC=C3)C4=CC=CC5=C4SC6=CC=CC=C56 | ||
| 分子式 | C25H19NO3S | 分子量 | 413.49 |
| 溶解度 | ≥ 4.13mg/mL in DMSO, <2.48 mg/mL in EtOH, <2.56 mg/mL in Water | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4184 mL | 12.0922 mL | 24.1844 mL |
| 5 mM | 0.4837 mL | 2.4184 mL | 4.8369 mL |
| 10 mM | 0.2418 mL | 1.2092 mL | 2.4184 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Quality Control & SDS
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- Purity: >99.50%
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