生物活性

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.

体外研究

体内研究

无菌 0.9% NaCl溶液

激酶实验

细胞实验

0.5 μM- 1 μM

动物实验

10 mg/kg 腹腔注射

不同实验动物依据体表面积的等效剂量转换表（数据来源于FDA指南）

例如，已知某工具药用于小鼠的剂量为88 mg/kg , 则用于大鼠的剂量换算方法：将88 mg/kg 乘以小鼠的Km系数（3），再除以大鼠的Km系数（6），得到该药物用于大鼠的等效剂量44 mg/kg。

参考文献

[1] Leahy JJ, et al. Bioorg Med Chem Lett, 2004, 14(24), 6083-6087.
[2] Willmore et al (2008) DNA-dependent protein kinase is a therapeutic target and an indicator of poor prognosis in B-cell chronic lymphocytic leukemia. Clin.Cancer Res. 14 3984.
[3] Robert et al (2015) Pharmacological inhibition of DNA-PK stimulates Cas9-mediated genome editing. Genome Med. 7 93.
[4] Zhao et al (2006) Preclinical evaluation of a potent novel DNA-dependent protein kinase inhibitor NU7441. Cancer Res. 66 5354.

体内溶解度

Clinical Trial Information ( data from http://clinicaltrials.gov )

注：以上所有数据均来自公开文献，并不保证对所有实验均有效，数据仅供参考。

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