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KU-60019

CAS No. : 925701-46-8

產品活性：KU-60019 is an improved ATM kinase-specific inhibitor with IC₅₀ of 6.3 nM.

研究領域：Cell Cycle/DNA Damage  |  PI3K/Akt/mTOR

作用靶點：ATM/ATR

In Vitro: KU-60019 is an improved analogue of KU-55933. KU-55933 has an IC₅₀ of 13 nM and K_i 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.

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).

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