SU-11752 is a potent and selective DNA-PK inhibitor. Inhibition kinetics and a direct assay for ATP binding showed that SU11752 inhibited DNA-PK by competing with ATP. SU11752 inhibited DNA double-strand break repair in cells and gave rise to a five-fold sensitization to ionizing radiation. At concentrations of SU11752 that inhibited DNA repair, cell cycle progression was still normal and ATM kinase activity was not inhibited.
SU-11752 is an inhibitor for DNA-dependent protein kinase (DNA-PK) with an IC50 of 0.13 μM. SU-11752 inhibits PI3K p110γ kinase with IC50 of 1.1 μM. SU-11752 binds competitively for ATP-site in DNA-PK, results in inhibition of intracellular DNA double-strand break repair and increases the sensitivity of cells to radiotherapy[1].
DNA-PK: 0.13 μM (IC50); p110γ: 1.1 μM (IC50)
[1] Ismail IH, et al., SU11752 inhibits the DNA-dependent protein kinase and DNA double-strand break repair resulting in ionizing radiation sensitization. Oncogene. 2004 Jan 29;23(4):873-82. DOI:
10.1038/sj.onc.1207303
