Are Cabozantinib Capecitabine Worth The Money?

As a handle, CP466722 and KU55933 had been shown to inhibit ATM kinase action while in the mouse pre B cells as demonstrated by disruption of p53 phosphorylation and p53 stabilization in response to IR.

Imatinib inhibited each one of these phosphorylation events, even though, CP466722 or KU55933 failed to inhibit BCRAbl kinase action or phosphorylation of downstream Cabozantinib targets. Although imatinib is not reported to directly inhibit Src kinase activity, cellular Src autophosphorylation was prevented by imatinib under these experimental conditions. Treatment with both CP466722 and KU55933 resulted in decreased Src autophosphorylation relative to the control cells. This data indicates that at doses capable of inhibiting ATM, CP466722 and KU55933 Capecitabine do not inhibit Abl kinase activity in cells, however, both compounds have inhibitory effects on Src kinase activity in this system.

A decrease in the percentage of mitotic cells following IR in the presence of DMSO indicated an IR induced G2 arrest, while both KU55933 and CP466722 prevented this IR induced decrease. In contrast to the effects seen with the less specific ATM/ATR inhibitor, caffeine, neither compound Capecitabine affected G2/M progression in the absence of DNA damage. Taken together the results demonstrate that CP466722 is capable of disrupting ATM function and recapitulates checkpoint defects reported for A T cells. KU55933 displays strong inhibition of ATM for at least 4h in tissue culture. To determine whether CP466722 could inhibit ATM for prolonged periods of time in tissue culture, HeLa cells were incubated with either DMSO, KU55933 or CP466722 for various times and then exposed to IR and harvested after a 30min recovery period.

Cells were subsequently exposed to IR at various times. In the presence of DMSO, the IR induced ATM dependent phosphorylation Capecitabine events were easily detected both before and after wash off.