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U0126-EtOH

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Chemical Structure| 1173097-76-1 同义名 : -
CAS号 : 1173097-76-1
货号 : A132258
分子式 : C20H22N6OS2
纯度 : 98%
分子量 : 426.558
MDL号 : MFCD22628895
存储条件：

粉末 Keep in dark place,Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(117.22 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

无水乙醇: 2 mg/mL(4.69 mM)，配合低频超声助溶，注意：无水乙醇开封后，易挥发，也会吸收空气中的水分，导致溶解能力下降，请避免使用开封较久的乙醇
动物实验配方：

IP 2% DMSO+2% Tween80+40% PEG300+water 6 mg/mL clear

PO 0.5% CMC-Na 35 mg/mL suspension

生物活性
靶点

  • MEK2

    MEK2, IC50:0.06 μM

  • MEK1

    MEK1, IC50:0.07 μM
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
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
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

[1]Duncia JV, Santella JB 3rd, et al. MEK inhibitors: the chemistry and biological activity of U0126, its analogs, and cyclization products. Bioorg Med Chem Lett. 1998 Oct 20;8(20):2839-44.

[2]Favata MF, Horiuchi KY, et al. Identification of a novel inhibitor of mitogen-activated protein kinase kinase. J Biol Chem. 1998 Jul 17;273(29):18623-32.

[3]Namura S, Iihara K, et al. Intravenous administration of MEK inhibitor U0126 affords brain protection against forebrain ischemia and focal cerebral ischemia. Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11569-74. Epub 2001 Aug 14.

[4]Kinehara M, Kawamura S, et al. Protein kinase C regulates human pluripotent stem cell self-renewal. PLoS One. 2013;8(1):e54122.

[5]Duan W, Chan JH, et al. Anti-inflammatory effects of mitogen-activated protein kinase kinase inhibitor U0126 in an asthma mouse model. J Immunol. 2004;172(11):7053-9.

[6]Bokemeyer D, Panek D, et al. In vivo identification of the mitogen-activated protein kinase cascade as a central pathogenic pathway in experimental mesangioproliferative glomerulonephritis. J Am Soc Nephrol. 2002;13(6):1473-80.