NU7441 (KU-57788)
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
NU7441是DNA依赖性蛋白激酶(DNA-PK)的选择性抑制剂,IC50值为13 nM [1]。
NU7441是DNA-PK的ATP竞争性抑制剂,Ki值为0.65 nM。其对DNA-PK的抑制是选择性的。NU7441在浓度高达100 μM时对DNA-PK相关性酶ATM和ATR没有抑制作用。NU7441对mTOR和PI3K具有抑制活性,IC50值分别为1.7和5 μM,比对DNA-PK的IC50值高约100倍。在HeLa细胞中,100 nM的NU7441显著增加细胞对etoposide的敏感性,促进细胞死亡。在SW620异种移植小鼠中,NU7441和etoposide联合使用引起5.4天的肿瘤生长延迟,比etoposide单独使用长两倍 [1,2]。
参考文献:
[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.
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- 4. 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
- 5. 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
- 6. 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
Storage | Store at -20°C |
M.Wt | 413.49 |
Cas No. | 503468-95-9 |
Formula | C25H19NO3S |
Synonyms | KU 57788; NU-7441;KU57788;NU7441;NU 7441 |
Solubility | insoluble in EtOH; insoluble in H2O; ≥4.13 mg/mL in DMSO |
Chemical Name | 8-dibenzothiophen-4-yl-2-morpholin-4-ylchromen-4-one |
SDF | Download SDF |
Canonical SMILES | C1COCCN1C2=CC(=O)C3=C(O2)C(=CC=C3)C4=CC=CC5=C4SC6=CC=CC=C56 |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 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。溶液形式一般不宜长期储存,请尽快用完。 |
细胞实验[1]: | |
细胞系 |
LoVo和SW620细胞 |
溶解方法 |
在DMSO中的溶解度 |
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. |
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 |
质量控制和MSDS
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