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。
CAS：942425-68-5
分子式：C12H12ClN3O
分子量：249.7
纯度：98%
存储：Store at -20°C

Background:

PHA-767491 hydrochloride is a dual Cdc7/Cdk9 inhibitor, with IC50s of 10 nM and 34 nM, respectively. CDK9|34 nM (IC50)|CDK2|240 nM (IC50)|CDK1|250 nM (IC50)|CDK5|460 nM (IC50)|GSK3-β|220 nM (IC50)|Mk2|470 nM (IC50)|Plk1|980 nM (IC50)|Chk2|1100 nM (IC50)

PHA-767491 inhibits proliferation in both cell lines with an IC50 of 0.64 µM in HCC1954 cells and 1.3 µM in Colo-205 cells. PHA-767491 is effective DDK inhibitors in vitro, with IC50 values of 18.6 nM. PHA-767491 (2 µM) completely abolishes Mcm2 phosphorylation by 24 hours in HCC1954 cells[1]. 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[2]. PHA-767491 (0-10 µM) decreases glioblastoma cell viability in a time- and dose-dependent fashion, with IC50 of approximately 2.5 µM for U87-MG and U251-MG cells. PHA-767491 hydrochloride induces apoptosis in glioblastoma cells, suppresses glioblastoma cell proliferation, cell migration and cell invasion[3].

PHA-767491 decreases Chk1 phosphorylation and increases in situ cell apoptosis in tumor tissues sectioned from nude mice HCC xenografts[2].

[1]. Sasi NK, et al. The potent Cdc7-Dbf4 (DDK) kinase inhibitor XL413 has limited activity in many cancer cell lines and discovery of potential new DDK inhibitor scaffolds. PLoS One. 2014 Nov 20;9(11):e113300. [2]. Li W, et al. Dual Inhibition of Cdc7 and Cdk9 by PHA-767491 Suppresses Hepatocarcinoma Synergistically with 5-Fluorouracil. Curr Cancer Drug Targets. 2015;15(3):196-204. [3]. Erbayraktar Z, et al. Cell division cycle 7-kinase inhibitor PHA-767491 hydrochloride suppresses glioblastoma growth and invasiveness. Cancer Cell Int. 2016 Nov 18;16:88. [4]. Montagnoli A, et al. A Cdc7 kinase inhibitor restricts initiation of DNA replication and has antitumor activity. Nat Chem Biol. 2008 Jun;4(6):357-65. [5]. Montagnoli A, et al. A Cdc7 kinase inhibitor restricts initiation of DNA replication and has antitumor activity. Nat Chem Biol. 2008 Jun;4(6):357-65.