PF-477736

Description	PF-477736 (128 nM) abrogates the camptothecin-induced DNA damage checkpoint in a dose-dependent manner in CA46 and HeLa cells. PF-477736 effectively abrogates the gemcitabine-induced S-phase arrest with a corresponding increase in apoptotic cell populations in HT29 cells. PF-477736 (540 nM) enhances gemcitabine-induced cytotoxicity in a time- and dose-dependent manner in HT29 cells. PF-477736 potentiates the growth-inhibitory activity of a panel of chemotherapeutic agents across a broad spectrum of p53-deficient human cancer cell lines in the MTT assay. Addition of PF-477736 (360 nM) to gemcitabine-arrested cells induces a dramatic increase in the intensity of H2AX phosphorylation, reflecting a greater number of γ-H2AX molecules near sites of DNA damage.PF-477736 (0.5 nM) selectively blocks p73 and P53 phosphorylation in presence of curcumin in HL-60 cells.PF-477736 (360 nM) suppresses docetaxel-induced phosphorylation of histone H3 (Ser10) and Cdc25C (Ser216) and potentiates apoptosis
Pathways	Cell Cycle/DNA Damage
Targets	Checkpoint

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