Biological Activity
KU-60019 is an improved ATM kinase-specific inhibitor with IC50 of 6.3 nM.
In Vitro
KU-60019 is an improved analogue of KU-55933. KU-55933 has an IC50 of 13 nM and Ki of 2.2 nM in vitro and is highly specific for the ATM kinase using a panel of 60 protein kinases. KU-60019 is an improved inhibitor of the ATM kinase with an IC50 of 6.3 nM, approximately half that of KU-55933. The IC50 values for DNA-PKcs and ATR are 1.7 and >10 μM, respectively, almost 270-and 1600-fold higher than for ATM. KU-60019 is 10-fold more effective than KU-55933 at blocking radiation-induced phosphorylation of key ATM targets in human glioma cells. In human U87 glioma cells, KU-55933 completely inhibits phosphorylation of p53 (S15) at 10 μM but not at 3 μM, whereas γ-H2AX levels are only partly reduced with 10 μM 1 h after irradiation. By comparison, 3 μM KU-60019 completely inhibits p53 phosphorylation and partial inhibits at 1 μM[1].
In Vivo
Despite PTEN-deficient control tumors reaching a 4-fold increase in size before PTEN wild-type controls, KU-60019-treated PTEN-deficient tumors display a statistically significant slowing in growth. This growth inhibition is especially evident at the start of the experiment (days 5-12) just after KU-60019 is administered (days 1-5)[2].
References & source
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.