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PHA-767491

Cat No.
CEI-0286
Description
PHA-767491
CAS No.
845714-00-3
Molecular Weight
213.24
Purity
>99%
Storage
2 years at -20 centigrade
Targets
Cdc7
Molecular Formula
C12H11N3O
Solubility
No
In vitro
PHA-767491 is a potent Cdc7 inhibitor. PHA-767491 is the first molecule that directly affects the mechanisms controlling initiation as opposed to elongation in DNA replication. PHA-767491 blocks DNA synthesis and affects the phosphorylation of the replicative DNA helicase at Cdc7-dependent phosphorylation sites. PHA-767491 prevents the activation of replication origins but does not impede replication fork progression, and it does not trigger a sustained DNA damage response. PHA-767491 induced apoptosis in all CLL samples tested with an average EC50 of 0.6 uM. PHA-767491 activates the intrinsic apoptotic pathway in resting CLL cells. Exposure of CLL cells to 1 uM PHA-767491 induced Bax activation occurs upstream of caspase activation. PHA-767491 induces downregulation of Mcl-1 protein in a caspase-independent manner. And DNA synthesis and Cdc7 activity of IL-4 and CD154-stimulated CLL cells can be inhibited by PHA-767491.
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