NU7441 | DNA-PK inhibitor

NU7441 (503468-95-9) is a potent (IC₅₀ = 13 nM) and selective ATP-competitive inhibitor of DNA-dependent protein kinase (DNA-PK).^1,2 It increased the toxicity of ionizing radiation and etoposide on SW620 human colon cancer lines via impeding DNA double-strand break repair.³ NU7441 also increased the radio/chemosensitivity of various other cancer cell lines.^3-6 Reduces the frequency of NHEJ repair while enhancing the rate of HDR repair following CRISPR/Cas9-mediated gene editing.⁷

References/Citations:

1) Leahy et al. (2004), Identification of a highly potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor (NU7441) by screening of chromenone libraries; Bioorg. Med. Chem. Lett., 14 6083
2) Hardcastle et al. (2005), Discovery of potent chromen-4-one inhibitors of the DNA-dependent protein kinase (DNA-PK) using a small-molecule library approach: J. Med. Chem., 48 7829
3) Zhao et al. (2006), Preclinical evaluation of a potent novel DNA-dependent protein kinase inhibitor NU7441: Cancer Res. 66 5354
4) Ciszewski et al. (2014), DNA-PK inhibition by NU7441 sensitizes breast cancer cells to ionizing radiation and doxorubicin: Breast Cancer Res. Treat., 143 83
5) Yang et al. (2016), NU7441 Enhances the Radiosensitivity of Liver Cancer Cells: Cell Physiol. Biochem., 38 1897
6) Geng et al. (2019), DNA-PKcs inhibitor increases the sensitivity of gastric cancer cells to radiotherapy: Oncol. Rep., 42 561
7) Robert et al. (2015), Pharmacological inhibition of DNA-PK stimulates Cas9-mediated genome editing: Genome Med., 7 93