CP-466722

2 years -80 in solvent

HeLa and A-T

In vitro, CP-466722 is identified as a potential inhibitor to decrease the activity of purified ATM kinase to phosphorylate GST-p53(1–101) substrate. In addition, CP-466722 also shows the inhibitory activities against abl and src kinases. [1], In HeLa cells, CP-466722 at doses of 6uM, results in the inhibition in ATM-dependent phosphorylation by reversibly inhibiting ionizing radiation (IR)-induced ATM kinase activity. Besides, ATM-dependent p53 induction is also inhibited by CP-466722 in MCF-7 human breast cancer cells and primary and immortalized diploid human fibroblasts. [1] In response to IR, CP-466722 increased proportion of cells with G2/M DNA content and reduces proportion of cells with G1-phase DNA content in HeLa cells. [1] Transient exposure to CP-466722 for a period of 4 hours sensitizes HeLa cells to IR without affecting cell plating nor cell viability. [1]

HeLa or A-T (GM02052 expressing hTERT) cells are plated in triplicate and incubated for 24 hours. Cells are pre-treated: DMSO, CP466722 or KU55933 prior to IR (0-10Gy). Cells are incubated for 4 hours following IR before media is removed, cells washed (PBS), trypsinsed, counted and re-plated (2000 cells/plate, 10 cm plates) in the absence of drug and incubated for 10 days. Prior to colony counting, cells are washed (PBS), stained (PBS, 0.0037%v/v-formaldehyde, 0.1%w/v-crystal violet), rinsed (dH2O) and dried. Defined populations (>50 cells) are counted as one surviving colony, data are calculated as percentage surviving colonies relative to control plates +/ SE.

CP-466722 is a potent and reversible ATM inhibitor, does not affect ATR and inhibits PI3K or PIKK family members in cells.