To exclude the off-target effect of KU0060648, especially its nature of ATP competitive inhibitor which can suppress the AKT activity, we investigated the inhibition of DNA-PKcs-AKT axis by KU0060648 after depleting DNA-PKcs in U87 and M059K (Supplementary Figure S7). RNAi specifically repressed the expression of DNA-PKcs and the activity of AKT. After knockdown of the DNA-PKcs, KU0060648 did not exert additional inhibitory effect on AKT phosphorylation. These findings indicated that KU0060648 was a specific inhibitor of DNA-PKcs rather than PI3K-AKT signaling, which was consistent with a previous study .