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NU 7026

现货
Catalog No.
A8649
有效的、竞争性DNA-PK抑制剂
组合的产品项目
规格价格库存 数量
10mg
¥ 750.00
现货
50mg
¥ 3,200.00
现货

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Background

NU 7026 is a selective inhibitor of  DNA-PK with IC50 value of 0.23 μM [1].
DNA-dependent protein kinase (DNA-PK) is a nuclear serine/threonine protein kinase and involves in a variety of cellular processes, like, DNA double-strand break (DSB) repair, V(D)J recombination apparatus, chromatin structure and telomere maintenance. It has been shown that increased DNA-PK expression resulted in tumor cells resistance to radio- or chemo- therapy [2].
NU 7026 is a potent DNA-PK inhibitor and often is used combined with PARP-1 inhibitor AG14361 to sensitize tumor cells to radio- or chemo-therapy. When tested with primary PARP-1-/- and cells PARP-1+/+ cells, NU 7026 treatment (<50 μM) sensitized cells to IR-induced cytotoxicity and reduced clonogenic survival by inhibiting DNA-PK [1]. In N87 gastric cancer cells, administration NU 7026 combined with radiation increased DNA double-srand break, cell apoptosis and reduced cell survival through inhibiting DNA-PK [2]. When tested with CH1 human ovarian cancer cells, administration of NU 7026 combined with radiation reduced cell survival rate and clonogenic ability [3].
In female BALB/c mice model with CH1 cells subcutaneous xenograft, administration of NU 7026 orally or intraperitoneally sensitized mice to the radiotherapy with the dose of 100 mg/kg [3].
It has also been reported that NU 7026 is a potent inhibitor of PI-3K, ATM and ATR with IC50 value of 13 μM, >100μM and >100μM, respectively [1].
References:
[1].    Veuger, S.J., et al., Radiosensitization and DNA repair inhibition by the combined use of novel inhibitors of DNA-dependent protein kinase and poly(ADP-ribose) polymerase-1. Cancer Res, 2003. 63(18): p. 6008-15.
[2].    Niazi, M.T., et al., Effects of dna-dependent protein kinase inhibition by NU7026 on dna repair and cell survival in irradiated gastric cancer cell line N87. Curr Oncol, 2014. 21(2): p. 91-6.
[3].    Nutley, B.P., et al., Preclinical pharmacokinetics and metabolism of a novel prototype DNA-PK inhibitor NU7026. Br J Cancer, 2005. 93(9): p. 1011-8.

Chemical Properties

StorageStore at -20°C
M.Wt281.31
Cas No.154447-35-5
FormulaC17H15NO3
Solubility<2.81mg/mL in DMSO
Chemical Name2-morpholin-4-ylbenzo[h]chromen-4-one
SDFDownload SDF
Canonical SMILESC1COCCN1C2=CC(=O)C3=C(O2)C4=CC=CC=C4C=C3
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

酶学实验[1]:

激酶检测

DNA-PK活性在30℃,最终体积为40μl,含有25mm HEPES(pH 7.4),12.5mm MgCl2,50mm KCl,1mm DTT,10%v/ v甘油,0.1%w/v NP-40和1mg GST-p53N66底物的聚丙烯96孔板中测定。加入不同浓度的抑制剂,孵育10分钟后,加入10μl ATP和30-mer双链DNA寡核苷酸起始反应。摇动1小时后,向反应物中加入150μl PBS,然后将5μl转移到每孔含有45μl PBS的96孔不透明白板中,孵育1小时。碱性ELISA检测由DNA-PK引发的p53丝氨酸15残基上的磷酸化事件。

细胞实验[1]:

细胞系

转染人DNA-PKcs基因的CHO V3细胞

溶解方法

在DMSO中的溶解度<2.81mg/mL。为了获得更高浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

10 μM

应用

在指数生长的DNA-PK精通细胞中,NU 7026可增强电离辐射的细胞毒性,可以作为有效的放射增敏剂,有作为抗癌治疗干预工具的潜力。

动物实验[2]:

动物模型

雌性BALB/c小鼠

剂量

腹腔注射,每天四次,每次100 mg/kg

应用

腹腔注射NU 7026可使小鼠对放射治疗敏感

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1] Veuger, S.J., et al., Radiosensitization and DNA repair inhibition by the combined use of novel inhibitors of DNA-dependent protein kinase and poly(ADP-ribose) polymerase-1. Cancer Res, 2003. 63(18): p. 6008-15.

[2] Nutley, B.P., et al., Preclinical pharmacokinetics and metabolism of a novel prototype DNA-PK inhibitor NU7026. Br J Cancer, 2005. 93(9): p. 1011-8.

生物活性

描述 NU 7026是一个有效的DNA-PK抑制剂,IC50值0.23 μM。
靶点 DNA-PK PI3K ATM      
IC50 0.23 μM 13 μM >100 μM      

质量控制

化学结构

NU 7026