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描述 | MEKs, which are members of the MAPKK family, can activate both ERK1 and ERK2 by catalyzing the phosphorylation on T202/Y204. Also MEK itself can be phosphorylated and activated through Ras when the upstream signaling is activated by extracellular stimuli, including growth factors, hormones etc.. U0126 is a selective MEK1/2 inhibitor with IC50 value of 70/60nM, but not ERK or Raf[1][2]. Co-treatment with U0126 for 15min at concentration ranging in 1nM-10μM caused inhibition of PMA-induced p-ERK, the target of MEK1/2 in a dose-dependent manner in COS-7 cells. An in vitro study showed that U0126 represented much more potency to both wild type and ΔN3-S218E/S222D MEK compared with the another MEK1/2 inhibitor, PD98059[2]. An in vivo study showed that U0126 is brain-permeable. Intravenous injection with U0126 at dose of 100mg/kg could reduce p-ERK1/2 in hippocampus after 10 min of reperfusion after 3.5 min bilateral carotid artery occlusion in male gerbils. Intravenous administration of U0126 at dose of 100-200mg/kg showed protective effect on the hippocampus against forebrain ischemia in male gerbils. Moreover, treatment with U0126 at 3 hours post ischemia significantly reduced volume after transient focal cerebral ischemia, accompanied with reduced p-ERK in the damaged brain areas[3]. Also, it has been reported that U0126 helped maintain human pluripotent stem cells[4]. | ||
作用机制 | U0126 is a non-competitive inhibitor of MEK1/2, which can bind a common or two overlapping sites on MEK.[2] |
细胞研究 | |||||
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细胞系 | 浓度 | 检测类型 | 检测时间 | 活动说明 | 数据源 |
COS-7 cells | Function assay | Inhibitory concentration against AP-1 transcription in COS-7 cells, IC50=1 μM. | 15006386 | ||
HCT116 cells | Function assay | Ability of compound to inhibit anchorage independent colony formation (soft agar growth assay) in HCT116 cells, IC50=19.4 μM. | 15225706 | ||
HeLa cells | Function assay | Inhibition of EGF-stimulated Elk1-luciferase reporter assay in HeLa cells, IC50=0.29 μM. | 15225706 |
实验方案 | |||
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1mg | 5mg | 10mg | |
1 mM 5 mM 10 mM |
2.63mL 0.53mL 0.26mL |
13.14mL 2.63mL 1.31mL |
26.28mL 5.26mL 2.63mL |
参考文献 |
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