产品号 #73522_C
MEK/ERK通路抑制剂；抑制MEK1和MEK2
总览
U-0126是一种选择性、非ATP竞争性丝裂原活化蛋白激酶激酶（MEK）抑制剂，其抑制MEK1和MEK2的IC₅₀值分别为72 nM和58 nM（Favata 等人；Scherle 等人）。在μM水平上，它对其他激酶（例如ERK、蛋白激酶C（PKC）、c-Jun N端激酶（JNK）、其他MAP激酶激酶（MKK3、MKK4、MKK6）、细胞周期依赖性激酶（CDK2、CDK4）、ABL和RAF）几乎没有或完全没有抑制作用（Favata et al. 1998）。U-0126还能拮抗AP-1转录，并选择性抑制含有AP-1反应元件的启动子（Favata et al.）。
维持培养与自我更新
·搭配bFGF、激活素A和PKC抑制剂，U-0126可促进人多能干细胞的维持培养（Kinehara et al.）。
·与MEF条件培养基单独使用时，U-0126可抑制人多能干细胞的自我更新，导致分化，而不影响增殖或存活（Li et al.）。
·抑制小鼠海马HT22细胞和大鼠原代皮质培养物中谷氨酸诱导的氧化应激（Satoh et al.; Ong et al.）。
·在沙鼠缺血模型和缺氧条件下培养的小鼠原代神经元中具有神经保护作用（Namura et al.）。
免疫学
·通过降低IL-2 mRNA水平抑制针对某些抗原刺激的T细胞增殖（DeSilva et al.）。
疾病建模
·激活过氧化物酶体增殖物激活受体（PPAR）共激活因子1α（PGC-1α）并预防受淀粉样蛋白β攻击的大鼠的神经毒性和空间记忆障碍（Ashabi et al.）。
细胞类型
神经元，多能干细胞，T 细胞
种属
人，小鼠，非人灵长类，其它细胞系，大鼠
应用
培养
研究领域
疾病建模，免疫，神经科学，干细胞生物学
CAS 编号
109511-58-2
化学式
C₁₈H₁₆N₆S₂
纯度
≥98%
通路
MEK/ERK
靶点
MEK1，MEK2
Protocols and Documentation
Find supporting information and directions for use in the Product Information Sheet or explore additional protocols below.
Applications
This product is designed for use in the following research area(s) as part of the highlighted workflow stage(s). Explore these workflows to learn more about the other products we offer to support each research area.
Resources and Publications
Educational Materials (3)
Publications (9)
U0126 protects cells against oxidative stress independent of its function as a MEK inhibitor. ACS chemical neuroscience 2015
Abstract
U0126 is a potent and selective inhibitor of MEK1 and MEK2 kinases. It has been widely used as an inhibitor for the Ras/Raf/MEK/ERK signaling pathway with over 5000 references on the NCBI PubMed database. In particular, U0126 has been used in a number of studies to show that inhibition of the Raf/MEK/ERK pathway protects neuronal cells against oxidative stress. Here, we report that U0126 can function as an antioxidant that protects PC12 cells against a number of different oxidative-stress inducers. This protective effect of U0126 is independent of its function as a MEK inhibitor, as several other MEK inhibitors failed to show similar protective effects. U0126 reduces reactive oxygen species (ROS) in cells. We further demonstrate that U0126 is a direct ROS scavenger in vitro, and the oxidation products of U0126 exhibit fluorescence. Our finding that U0126 is a strong antioxidant signals caution for its future usage as a MEK inhibitor and for interpreting some previous results.
Protein kinase C regulates human pluripotent stem cell self-renewal. PloS one 2013
Abstract
BACKGROUND: The self-renewal of human pluripotent stem (hPS) cells including embryonic stem and induced pluripotent stem cells have been reported to be supported by various signal pathways. Among them, fibroblast growth factor-2 (FGF-2) appears indispensable to maintain self-renewal of hPS cells. However, downstream signaling of FGF-2 has not yet been clearly understood in hPS cells. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we screened a kinase inhibitor library using a high-throughput alkaline phosphatase (ALP) activity-based assay in a minimal growth factor-defined medium to understand FGF-2-related molecular mechanisms regulating self-renewal of hPS cells. We found that in the presence of FGF-2, an inhibitor of protein kinase C (PKC), GF109203X (GFX), increased ALP activity. GFX inhibited FGF-2-induced phosphorylation of glycogen synthase kinase-3β (GSK-3β), suggesting that FGF-2 induced PKC and then PKC inhibited the activity of GSK-3β. Addition of activin A increased phosphorylation of GSK-3β and extracellular signal-regulated kinase-1/2 (ERK-1/2) synergistically with FGF-2 whereas activin A alone did not. GFX negated differentiation of hPS cells induced by the PKC activator, phorbol 12-myristate 13-acetate whereas Gö6976, a selective inhibitor of PKCα, β, and γ isoforms could not counteract the effect of PMA. Intriguingly, functional gene analysis by RNA interference revealed that the phosphorylation of GSK-3β was reduced by siRNA of PKCδ, PKCε, and ζ, the phosphorylation of ERK-1/2 was reduced by siRNA of PKCε and ζ, and the phosphorylation of AKT was reduced by PKCε in hPS cells. CONCLUSIONS/SIGNIFICANCE: Our study suggested complicated cross-talk in hPS cells that FGF-2 induced the phosphorylation of phosphatidylinositol-3 kinase (PI3K)/AKT, mitogen-activated protein kinase/ERK-1/2 kinase (MEK), PKC/ERK-1/2 kinase, and PKC/GSK-3β. Addition of GFX with a MEK inhibitor, U0126, in the presence of FGF-2 and activin A provided a long-term stable undifferentiated state of hPS cells even though hPS cells were dissociated into single cells for passage. This study untangles the cross-talk between molecular mechanisms regulating self-renewal and differentiation of hPS cells.
ERK and p38 inhibitors attenuate memory deficits and increase CREB phosphorylation and PGC-1α levels in Aβ-injected rats. Behavioural brain research 2012
Abstract
In this study, we investigated the effect of intracerebroventricular administration of ERK and p38 specific inhibitors, U0126 and PD169316, respectively, on learning and memory deficits induced by amyloid beta (Aβ) in rats. To investigate the effects of these compounds on learning and memory, we performed Morris water maze (MWM) test. U0126 and/or PD169316 improved spatial learning in MWM in Aβ-injected rats, 20 days after Aβ-injection. To determine the mechanisms of action of U0126 and PD169316, we studies their effect on some intracellular signaling pathways such as Ca(+)/cAMP-response element binding protein (CREB), c-fos, and transcription factors that regulate mitochondrial biogenesis. Based on our data, CREB and c-fos levels decreased 7 days after Aβ-injection, while U0126 and/or PD169316 pretreatments significantly increased these levels. Moreover, U0126 and PD169316 activated peroxisome proliferator-activated receptor gamma coactivator-1a, nuclear respiratory factor 1, and mitochondrial transcription factor A, 7 days after Aβ-injection. Surprisingly, these factors were returned to vehicle level, 20 days after Aβ-injection. Our findings reinforce the potential neuroprotective effect of these inhibitors against the Aβ toxicity.
更多信息
| Species | Human, Mouse, Non-Human Primate, Other, Rat |
|---|---|
| Cas Number | 109511-58-2 |
| Chemical Formula | C₁₈H₁₆N₆S₂ |
| Purity | ≥ 98% |
| Target | MEK1, MEK2 |
| Pathway | MEK/ERK |
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