3'-Phosphoinositide-dependent protein kinase 1 (PDK-1) phosphorylates and activates members of the AGC protein kinase family and plays an important role in the regulation of cell survival, differentiation, and proliferation[3]. OSU-03012 is a PDK-1 inhibitor with an IC50 of 5 μM. OSU-03012 induces apoptotic death in PC-3 cells in 1% FBS-containing medium in a dose-dependent manner, as demonstrated by DNA fragmentation and PARP cleavage. It is effective in suppressing PC-3 cell proliferation at sub-μM, consistent with that noted in 1% serum. OSU-03012 was able to completely suppress cell growth in a diverse range of tumor cell lines at the 3-5 μM therapeutic range, as compared with the concentration of at least 50 μM required for celecoxib[4]. OSU-03012 inhibited cell growth of Huh7, Hep3B, and HepG2 cells with IC50 below 1 mumol/L[5]. Daily oral treatment of BALB/c nude mice with OSU-03012 suppressed the growth of Huh7 tumor xenografts. Electron microscopic observation indicated that OSU-03012 induced autophagy in vivo[5]. OSU-03012 remarkably decreases EGFR protein expression in the tumors by ~48% compared with expression levels found in the tumors taken from mice that receive the vehicle control. OSU-03012 also prevents Y-box binding protein-1 (YB-1) from binding to the EGFR promoter at the 1b and 2a sites[6].
作用机制
The guanidino group of OSU-03012 resembled the partial structure of the purine ring of ATP, which allowed the formation of hydrogen bonds with Ser160 and Ala162 as depicted by the docking model.
OSU-03012 细胞研究
细胞系
浓度
检测类型
检测时间
活动说明
数据源
mouse RAW264.7 cells
Function assay
8 h
Antimicrobial activity against Salmonella enterica serovar Typhimurium ATCC 14028 infected in mouse RAW264.7 cells assessed as inhibition of intracellular bacterial growth after 8 hrs, IC50=0.2 μM
19805568
mouse RAW264.7 cells
Cytotoxic assay
24 h
Cytotoxicity against mouse RAW264.7 cells assessed as cell viability after 24 hrs by MTT assay, IC50=10 μM
搜索
