KU-55933 (10 μM) blocks the ionizing radiation-induced p53 serine 15 phosphorylation. KU-55933 has a dose-dependent effect in inhibiting this ATM-dependent phosphorylation event with an estimated IC50 of 300 nM. KU-55933 ablates the ionizing radiation-induced phosphorylation of these ATM substrates. KU-55933 specifically inhibits ATM but not the other DNA damage-activated PIKKs, ATR, and DNA-PK. KU-55933 induces pATM, p53, E2F1 and pATR, noticeably upregulates the nuclear fraction of E2F1 at the 0.5 h time point. Metformin increases ATM and AMPK phosphorylation, as well as SHP protein level in primary hepatocytes, and this stimulatory effect of metformin is repressed by a specific ATM kinase inhibitor KU-55933.
Medlife has not independently confirmed the accuracy of these methods. They are for reference only.