KU-55933

KU-55933 is a potent ATM inhibitor with an IC₅₀ and K_i of 12.9 and 2.2 nM, respectively, and is highly selective for ATM as compared to DNA-PK, PI3K/PI4K, ATR and mTOR. IC50 & Target: IC50: 12.9 nM (ATM)^[1] In Vitro: 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^[1]. KU-55933 induces pATM, p53, E2F1 and pATR, noticeably upregulates the nuclear fraction of E2F1 at the 0.5 h time point^[2]. 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^[3].