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 : GC11251A selective DNA-PK inhibitor
Cas No.:503468-95-9
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: [1] | |
Cell lines |
LoVo and SW620 cells |
Preparation method |
The solubility of this compound in DMSO is |
Reaction Conditions |
1 μM, 16 hours |
Applications |
To investigate the effects of NU7441 on the cell cycle phase distribution, LoVo and SW620 cells were treated with NU7441 for 16 hours, with and without 2Gy ionizing radiation or coincident 16 hours of exposure to etoposide or doxorubicin, by flow cytometry. NU7441 alone caused a modest 15% increase in G1, with consequent 24% reduction in the S phase in p53 mutant SW620 cells. In the p53 wt LoVo cells, NU7441 caused a more substantial 54% increase in G1 and 72% decrease in S phase in accordance with its pronounced growth inhibitory effect in this cell line. |
Animal experiment: [1] | |
Animal models |
CD-1 nude mice bearing SW620 cancer xenografts |
Dosage form |
Intraperitoneal injection, 10 mg/kg |
Applications |
Mice were treated with normal saline (contro animals), single agent NU7441 (dissolved in 40% PEG 400 in saline), or etoposide phosphate (11.35 mg/kg in saline) i.p. daily for 5 days. For combinations, NU7441 was given immediately before etoposide phosphate. Tumors in control mice reached four times their starting volume (RTV4) at a median time of 5.6 days (i.e., time to RTV4 = 5.6 days). Treatment with etoposide phosphate alone caused a tumor growth delay of 2.7 days (time to RTV4 = 8.3 days), which was extended to 5.4 days (time to RTV4 = 11 days, P = 0.0159 compared with etoposide alone) by coadministration of NU7441. Thus, NU7441 enhanced etoposide phosphate efficacy by 100%. |
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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. |
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.
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 | |||
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 |
第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量) | ||||||||||
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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。