NU7441 (KU-57788) as NHEJ Inhibitors
Biological Activity
NU7441 selectively inhibits DNA-dependent protein kinase (DNA-PK), a DNA repair enzyme that catalyzes NHEJ, required to repair lethal DSBs. It exhibits ATP-competitive inhibition kinetics, reducing the frequency of NHEJ while increasing the rate of HDR. [1]
| Target (in cell-free assays) | IC50[ 1 ] |
| DNA-PK | 14 nm |
| mTOR | 1.7 μM |
| PI3K | 5 μM |
| Ataxia telangiectasia mutated kinase (ATM) | >100 μM |
| Ataxia telangiectasia and Rad3 related kinase (ATR) | >100 μM |
Successful Applications in CRISPR
A three- to four-fold increase in HDR was observed upon treatment of 293/TLR cells with NU7441 via ss- or ds- donors. A two-fold decrease in NHEJ-mediated repair events was also observed. [2]
Reference:
- Leahy, J. J., Golding, B. T., Griffin, R. J., Hardcastle, I. R., Richardson, C., Rigoreau, L., & Smith, G. C. (2004). Identification of a highly potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor (NU7441) by screening of chromenone libraries. Bioorganic & medicinal chemistry letters, 14(24), 6083–6087.
- Robert, F., Barbeau, M., Éthier, S., Dostie, J., & Pelletier, J. (2015). Pharmacological inhibition of DNA-PK stimulates Cas9-mediated genome editing. Genome medicine, 7(1), 93.
Related Product:
920259 KU-57788, 98%, a potent and selective inhibitor of DNA-PK [CAS: 503468-95-9]
