Cell lines

U87 and U1242 cells

Preparation method

The solubility of this compound in DMSO is >27.4 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 ℃ for several months.

Reacting condition

3 μM; 1, 3 and 5 days

Applications

In U87 cells, KU-60019 at 3 μM significantly inhibited cell migration and invasion by >70% and ~ 60%, respectively. Similarly, KU-60019 also substantially inhibited migration and invasion of human glioma U1242 cells by >50% and ~ 60%, respectively.

Animal models

Athymic female mice implanted with U1242/luc-GFP cells

Dosage form

KU-60019 (10 μM) delivered intratumorally at a rate of 0.5 μL/h by osmotic pump, for 14 days

Applications

In athymic female mice implanted with U1242/luc-GFP cells, the combination of KU-60019 and radiation significantly inhibited tumor growth than radiation alone, which suggested that KU-60019 might radiosensitize U1242 gliomas.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

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].

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.