Ku-60019 is a potent, reversible inhibitor of ATM kinase (IC50: 6.3 nM). It is much less effective or without effect against a panel of 229 other kinases.

ATM:6.3 nM (cell free)

KU-60019是ATM激酶的一种改良型抑制剂，其IC50值为6.3 nM，大约是KU-55933的一半。对于DNA-PKcs和ATR的IC50值分别为1.7和>10 μM，分别是对ATM的近270倍和1600倍[1]。KU-60019在300 nM的浓度下，可以在应用后最快15分钟内完全抑制p53和H2AX的磷酸化。当U1242细胞经KU-60019处理1小时后，洗去KU-60019再经IR挑战，KU-60019的抑制效果在洗去后最早的15分钟内即被逆转[2]。

尽管PTEN缺失型对照肿瘤在PTEN野生型对照前达到了4倍的体积增长，但经KU-60019处理的PTEN缺失型肿瘤显示出了统计学上的显著生长减缓，这种生长抑制在实验开始阶段（第5-12天）尤为明显，正好是在给予KU-60019治疗后（第1-5天）[3]。当使用渗透泵给予KU-60019处理并随后对携带U1242/luc-GFP肿瘤的小鼠进行2 Gy辐射照射时，我们通过生物发光成像（BLI）在辐射后第7天，即第20天成功证明了肿瘤细胞的完全消除[4]。

Cell growth was determined by AlamarBlue. U1242 cells were serially diluted, allowed to attach for 6 h and then exposed to KU-60019 at 3 μM. At days 1, 3 and 5 after seeding, AlamarBlue was added to the medium to the recommended final concentration. Plates were incubated for 1 h at 37°C and fluorescence determined on a FluoroCount plate reader (excitation 530 nm, emission 590 nm) and values taken as a measure of cell growth [1].

Cells (3 × 10^7) were implanted into male Fox Chase Severe Combined Immunodeficiency (SCID) mice. Administration of doxycycline was started when tumors reached 100 mm3 in volume and was performed every 48 hours up to removal of the animal from the experiment. Forty-eight hours after PTEN induction, animals were administered KU-60019 (100 mg/kg) for 5 consecutive days and measured until they reached a target 400 mm3 volume. Measurements of tumor volume and body weight took place every 3 days using calipers [3].