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NU7441 (KU-57788)

现货
Catalog No.
A8315
DNA-PK抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 950.00
现货
5mg
¥ 500.00
现货
25mg
¥ 1,500.00
现货

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Background

NU7441 is a selective inhibitor of DNA-dependent protein kinase (DNA-PK) with IC50 value of 13 nM [1].

NU7441 is an ATP-competitive inhibitor of DNA-PK and showed a Ki value of 0.65 nM. The inhibition of DNA-PK was selective. NU7441 showed no inhibition effect on the DNA-PK-related enzymes ATM and ATR at concentration of 100 μM. For mTOR and PI3K, NU7441 exerted inhibition activities with IC50 values of 1.7 and 5 μM, respectively, which were about 100-fold higher than the IC50 value of DNA-PK. In HeLa cells, treatment of NU7441 at concentration of 100 nM significantly enhanced the sensitivity of cells to etoposide and promoted cells to death. In mice bearing SW620 xenografts, coadministration of NU7441 and etoposide caused a tumor growth delay of 5.4 days which was twice longer than that caused by etoposide alone [1, 2].

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. Journal of medicinal chemistry, 2005, 48(24): 7829-7846.
[2] Zhao Y, Thomas H D, Batey M A, et al. Preclinical evaluation of a potent novel DNA-dependent protein kinase inhibitor NU7441. Cancer research, 2006, 66(10): 5354-5362.

文献引用

1. Piekna-Przybylska D, Nagumotu K, et al. "HIV-1 infection renders brain vascular pericytes susceptible to the extracellular glutamate." J Neurovirol. 2018 Nov 6. PMID:30402824
2. Piekna-Przybylska D, Maggirwar SB. "CD4+ memory T cells infected with latent HIV-1 are susceptible to drugs targeting telomeres." Cell Cycle.2018;17(17):2187-2203. PMID:30198385
3. Piekna-Przybylska D, Sharma G, et al. "Deficiency in DNA damage response, a new characteristic of cells infected with latent HIV-1." Cell Cycle. 2017 May 19;16(10):968-978. PMID:28388353
4. Rulina AV, Mittler F, et al. "Distinct outcomes of CRL-Nedd8 pathway inhibition reveal cancer cell plasticity." Cell Death Dis. 2016 Dec 1;7(12):e2505. PMID:27906189

Chemical Properties

StorageStore at -20°C
M.Wt413.49
Cas No.503468-95-9
FormulaC25H19NO3S
SynonymsKU 57788; NU-7441;KU57788;NU7441;NU 7441
Solubility≥4.13mg/mL in DMSO, <2.48 mg/mL in EtOH, <2.56 mg/mL in H2O
Chemical Name8-dibenzothiophen-4-yl-2-morpholin-4-ylchromen-4-one
SDFDownload SDF
Canonical SMILESC1COCCN1C2=CC(=O)C3=C(O2)C(=CC=C3)C4=CC=CC5=C4SC6=CC=CC=C56
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

细胞实验[1]:

细胞系

LoVo和SW620细胞

溶解方法

在DMSO中的溶解度<10 mM。为了获得更高的浓度,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

1 μM;16 h

应用

LoVo和SW620细胞用NU7441处理16小时,在2Gy电离辐射存在和不存在,或同时暴露于etoposide或doxorubicin 16小时,用流式细胞仪评估NU7441对细胞周期相分布的影响。在p53突变的SW620细胞中,NU7441单独给药引起G1期15%的增加及相应S期24%的减少。在p53 wt LoVo细胞中,NU7441引起较大幅度的G1期增加(54%)和S期减少(72%),与其在该细胞系中显著的生长抑制效应一致。

动物实验[1]:

动物模型

SW620肿瘤异种移植CD-1裸鼠

剂量

10 mg/kg;腹腔注射

应用

小鼠分别用生理盐水(对照动物)、NU7441(溶于40% PEG 400的生理盐水)或etoposide phosphate(11.35 mg/kg,溶于生理盐水)通过腹腔注射(i.p.)的方式给药5天。对于联合给药,etoposide phosphate给药之前注射NU7441。在对照小鼠中,肿瘤达到初始体积的4倍(RTV4)所用的中值时间是5.6天,etoposide phosphate单独治疗引起2.7天的肿瘤生长延迟(达到RTV4的时间是8.3天)。而与NU7441联合治疗后,引起了5.4天的肿瘤生长延迟(达到RTV4的时间是11天,与etoposide单独给药相比,P = 0.0159)。因此,NU7441增强了100%的etoposide phosphate的效力。

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] Zhao Y, Thomas H D, Batey M A, et al. Preclinical evaluation of a potent novel DNA-dependent protein kinase inhibitor NU7441. Cancer research, 2006, 66(10): 5354-5362.

生物活性

描述 NU7441 (KU-57788)是一种高效的和选择性的DNA-PK抑制剂,IC50值为14 nM;也可以抑制PI3K,IC50值为5 μM。
靶点 DNA-PK          
IC50 14 nM          

质量控制

化学结构

NU7441 (KU-57788)

相关生物数据

NU7441 (KU-57788)

相关生物数据

NU7441 (KU-57788)

相关生物数据

NU7441 (KU-57788)

相关生物数据

NU7441 (KU-57788)

相关生物数据

NU7441 (KU-57788)

相关生物数据

NU7441 (KU-57788)