KU-60019

The Uses of KU-60019

KU-60019 has been used to block ataxia telangiectasia mutated (ATM), to study its association of with the regulation of H2AX (H2A histone family, member X) and apoptosis inducing factor (AIF)-mediated cell death.

Biological Activity

ku-60019 is a selective inhibitor of the ataxia telangiectasia (a-t) mutated (atm) protein with an ic50 value of 6.3 nm. in literature report, ku-60019 radiosensitizes h-tert-immortalized normal fibroblasts but not a-t fibroblasts, suggesting it is a specific atm kinase radiosensitizer [1].ku-60019 can reduce radiation-induced s473 akt phosphorylation in human glioma cell lines that are p53 wild type (u87) and p53 mutant (u1242). however, the suppression of akt does not enhance radiosensitization of ku-60019 [1].ku-60019 has been reported to inhibit cell migration and invasion in human glioma cells u87 and u1242 in a dose-dependent manner. besides, ku-60019, to some extent, has also been shown to suppress the growth of u1242 cells [1].

Biochem/physiol Actions

KU-60019 is a potent inhitor of ATM (ataxia telangiectasia mutated) kinase, a member of phosphatidylinositol-3-kinase-related kinase family that is critical in regulating cell cycle checkpoints and DNA repair. KU-60019 has an IC50 value of 6.3 nM. KU-60019 radiosensitizes U1242 human glioma cells, and also blocks U1242 cell migration and invasion through matrigel.

References

[1] golding se1, rosenberg e, valerie n, hussaini i, frigerio m, cockcroft xf, chong wy, hummersone m, rigoreau l, menear ka, o'connor mj,povirk lf, van meter t, valerie k. improved atm kinase inhibitor ku-60019 radiosensitizes glioma cells, compromises insulin, akt and erk prosurvival signaling, and inhibits migration and invasion. mol cancer ther. 2009 oct;8(10):2894-902.