DNA-PK Inhibitor III is a cell-permeable aryl-morpholino compound that is potent, selective, and an ATP-competitive inhibitor of DNA-PK (IC50= 120 nM) and PI 3-Kinase catalytic subunit p110β (IC50= 135 nM). Inhibits DNA-PK-mediated cellular DNA DSB (double strand break) repair (EC50= 68 μM) and enhances DSB-induced antitumor activity in vitro, while exhibiting no cytotoxic effects (up to 50 μM) in the absence of DSBs. Also inhibits PI 3K p110α, p110γ, and p110δ only at much higher concentrations (IC50= 1.4 μM, 880 nM, and 1.0 μM, respectively) and exhibits no effect against a panel of several other kinases, including, Cdk2, Src, PKA, PKC, Chk1, CK1, ATM, and FKBP12, even at concentrations as high as 100 μM.
