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PHA-767491 hydrochloride

CAS No. : 942425-68-5

MCE 站：PHA-767491 hydrochloride

产品活性：PHA-767491 hydrochloride 是一种 Cdc7-Dbf4 (DDK)/Cdk9 的双重抑制剂，IC₅₀ 值分别为 10 nM 和 34 nM。

研究领域：Cell Cycle/DNA Damage  |  Apoptosis

作用靶点：CDK  |  Apoptosis

In Vitro: PHA-767491 inhibits proliferation in both cell lines with an IC₅₀ of 0.64 ?M in HCC1954 cells and 1.3 ?M in Colo-205 cells. PHA-767491 is effective DDK inhibitors in vitro, with IC₅₀ values of 18.6 nM. PHA-767491 (2 ?M) completely abolishes Mcm2 phosphorylation by 24 hours in HCC1954 cells. PHA-767491 in combination with 5-FU exhibits much stronger cytotoxicity and induces significant apoptosis manifested by remarkably increased caspase 3 activation and poly(ADP-Ribose) polymerase fragmentation in HCC cells. PHA-767491 directly counteracts the 5-FU-induced phosphorylation of Chk1 and decreases the expression of the anti-apoptotic protein myeloid leukemia cell 1ine. PHA-767491 (0-10 ?M) decreases glioblastoma cell viability in a time- and dose-dependent fashion, with IC₅₀ of approximately 2.5 ?M for U87-MG and U251-MG cells. PHA-767491 hydrochloride induces apoptosis in glioblastoma cells, suppresses glioblastoma cell proliferation, cell migration and cell invasion.

In Vivo: PHA-767491 decreases Chk1 phosphorylation and increases in situ cell apoptosis in tumor tissues sectioned from nude mice HCC xenografts.

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