One such drug, AZD7762, produced by AstraZeneca, is an ATP-competitive checkpoint kinase inhibitor that assists DNA-damaging drugs by blocking the checkpoint response (reviewed in [ 55]).
To confirm that the effects of UCN-01 are related to CHK1 inactivation, cells were also dosed alone and in combination with sub IC50 concentrations of gemcitabine and AZD 7762, an ATP-competitive checkpoint kinase inhibitor [ 11], and assayed for proliferation.
Two closely related binding modes have previously been proposed for the ATP-competitive benzimidazole class of checkpoint kinase 2 (CHK2) inhibitors; however, neither binding mode is entirely consistent with the reported SAR.
We have learned from animal models of bone marrow failure and MDS as well as patients' subgroups that cells with activated checkpoint signaling display competitive disadvantages.
As a control for checkpoint override, we used reversine, a bona fide ATP-competitive inhibitor of the spindle checkpoint kinase Mps1 (Santaguida et al, 2010).
Hydroxyurea is a competitive inhibitor of ribonucleotide reductase which interferes with deoxyribonucleotide synthesis, resulting in deoxyribonucleotide depletion, fork stalling and checkpoint activation [3].
A recent study has revealed a crucial complex in kinetochores called KMN which can bind microtubules and checkpoint proteins (especially binding Bub3 directly) in corresponding checkpoint "off" and "on", respectively [61], indicating a competitive relationship between microtubules and Bub3.
Seavey is twenty-six, a puppy by competitive mushing's wizened standards, and reluctant to grow the kind of mustache that collects snow and sprouts icicles on long runs, making for a dramatic arrival at race checkpoints.
I pass a police checkpoint.
Traffic slowed near the checkpoint.
