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].

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.