U0126-EtOH
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
U0126-EtOH是一种选择性的MEK1和MEK2抑制剂，IC50值分别为70 nM和60 nM [1]。
U0126作为抗炎剂而被筛选到，抑制AP-1转录，IC50值为1 μM，与GREs没有相互作用。U0126与MEK1/2特异性的位点结合，对MEK1/2的抑制与ERK和ATP是非竞争性的。U0126对其它的MAPKKs没有影响。在HT22细胞中，U0126显著抑制氧化谷氨酸毒性引起的细胞损伤，并显著阻断ERK1/2的磷酸化。除此之外，U0126对其它刺激没有神经保护作用，如TNFα和放线菌素D。U0126也可以保护原代培养皮层神经元免受氧化谷氨酸毒性和缺氧/复氧造成的损伤 [1,2]。
参考文献：
[1] Duncia J V, Santella III J B, Higley C A, et al. MEK inhibitors: the chemistry and biological activity of U0126, its analogs, and cyclization products. Bioorganic & Medicinal Chemistry Letters, 1998, 8(20): 2839-2844.
[2] Satoh T, Nakatsuka D, Watanabe Y, et al. Neuroprotection by MAPK/ERK kinase inhibition with U0126 against oxidative stress in a mouse neuronal cell line and rat primary cultured cortical neurons. Neuroscience letters, 2000, 288(2): 163-166.
- 1. Nianshuang Li, Xinbo Xu, et al. "Activation of Aquaporin 5 by carcinogenicHelicobacter pyloriinfection promotes epithelial‐mesenchymal transition via the MEK/ERK pathway." Helicobacter. 2021;00:e12842.
- 2. Danhui Liu, Yuzhen Liu, et al. "Trichostatin A promotes esophageal squamous cell carcinoma cell migration and EMT through BRD4/ERK1/2-dependent pathway." Cancer Med. 2021 Aug;10(15):5235-5245. PMID: 34160902
- 3. Xiaoli Liu, Yan Gu, et al. "Honokiol induces paraptosis-like cell death of acute promyelocytic leukemia via mTOR & MAPK signaling pathways activation." Apoptosis. 2021 Apr;26(3-4):195-208. PMID: 33550458
- 4. Ha SD, Cho W, et al. "The transcription factor PU.1 mediates enhancer-promoter looping that is required for IL-1β eRNA and mRNA transcription in mouse melanoma and macrophage cell lines." J Biol Chem. 2019 Nov 15;294(46):17487-17500. PMID: 31586032
- 5. Liu W, Zhan C, et al. "Microcystin-LR influences the in vitro oocyte maturation of zebrafish by activating the MAPK pathway." Aquat Toxicol. 2019 Oct;215:105261. PMID: 31419757
- 6. White SM, Avantaggiati ML, et al. "YAP/TAZ Inhibition Induces Metabolic and Signaling Rewiring Resulting in Targetable Vulnerabilities in NF2-Deficient Tumor Cells." Dev Cell. 2019 May 6;49(3):425-443.e9. PMID: 31063758
- 7. Huang SZ, Wei MN, et al. "Targeting TF-AKT/ERK-EGFR Pathway Suppresses the Growth of Hepatocellular Carcinoma." Front Oncol. 2019 Mar 15;9:150. PMID: 30931258
- 8. Wang Q, Zhou C, et al. "The involvement of the ERK-MAPK pathway in TGF-β1-mediated connexin43-gap junction formation in chondrocytes. Connect Tissue Res." 2019 Mar 22:1-10. PMID: 30897973
- 9. Vincent Picher-Martel. "L’implication de l’ubiquiline-2 dans l’agrégation de TDP-43 et la pathogénèse de la sclérose latérale amyotrophique." University Laval. 2019.
- 10. Chen M, Ye K, et al. "Paris Saponin II inhibits colorectal carcinogenesis by regulating mitochondrial fission and NF-κB pathway." Pharmacol Res. 2018 Nov 22;139:273-285. PMID: 30471409
- 11. Zhu Y, Li Q, et al. "TLR activation inhibits the osteogenic potential of human periodontal ligament stem cells through Akt signaling in a Myd88- or TRIF-dependent manner." J Periodontol. 2018 Oct 26. PMID: 30362568
- 12. MXinwei Feng1, Junfeng Lu2, et al. "Mycobacterium smegmatis Induces Neurite Outgrowth and Differentiation in an Autophagy-Independent Manner in PC12 and C17.2 Cells." Front. Cell. Infect. Microbiol., 19 June 2018.
- 13. Lu YT, Li LZ, et al."Succinate induces aberrant mitochondrial fission in cardiomyocytes through GPR91 signaling." Cell Death Dis. 2018 Jun 4;9(6):672. PMID: 29867110
- 14. Ma L, Jiang Y, et al. "Anti-TNF-alpha antibody attenuates subarachnoid hemorrhage-induced apoptosis in the hypothalamus by inhibiting the activation of Erk." Neuropsychiatr Dis Treat. 2018 Feb 15;14:525-536. PMID: 29497296
- 15. Sieber J, Wieder N, et al. "GDC-0879, a BRAF(V600E) Inhibitor, Protects Kidney Podocytes from Death." Cell Chem Biol. 2017 Dec 6. PMID: 29249695
- 16. Wang HY, Wang W, et al. "Role of KCNB1 in the prognosis of gliomas and autophagy modulation." Sci Rep. 2017 Feb 8;7(1):14. PMID: 28144039
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 426.56 |
| Cas No. | 1173097-76-1 |
| Formula | C18H16N6S2·C2H6O |
| Solubility | ≥21.33 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH |
| Chemical Name | (2Z,3Z)-2,3-bis[amino-(2-aminophenyl)sulfanylmethylidene]butanedinitrile;ethanol |
| SDF | Download SDF |
| Canonical SMILES | CCO.C1=CC=C(C(=C1)N)SC(=C(C#N)C(=C(N)SC2=CC=CC=C2N)C#N)N |
| 运输条件 | 蓝冰运输或根据您的需求运输。 |
| 一般建议 | 不同厂家不同批次产品溶解度各有差异，仅做参考。若实验所需浓度过大至产品溶解极限，请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存，请尽快用完。 |
| 细胞实验 [1]: | |
|
细胞系 |
HT22细胞 |
|
溶解方法 |
该化合物在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液，一般步骤如下：请将试管置于37°C加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20°C可放置数月。 |
|
反应条件 |
10 μM, 24小时 |
|
实验结果 |
使用含或不含不同浓度抑制剂的5mM谷氨酸溶液处理细胞，处理后24小时，通过MTT测定法测定HT22细胞的活力。结果表明，U0126以剂量依赖性方式抑制谷氨酸毒性引起的细胞死亡。10 μM的U0126可以特异性抑制MEK1/2，在此浓度下，U0126可以完全抑制细胞损伤。 |
| 动物实验[2]: | |
|
动物模型 |
雄性BALB/c 小鼠 |
|
剂量 |
腹腔注射，7.5、15和30 mg/kg |
|
实验结果 |
通过腹腔注射20 μg OVA和4 mg的Al(OH)3使小鼠致敏。在最后一次OVA气溶胶攻击后24小时收集BAL液。与PEG对照相比，U0126（7.5、15和30 mg/kg）显著降低了BAL液中回收的总细胞数，这主要是由于U0126以剂量依赖性的方式显著减少嗜酸性粒细胞的数量。在用盐水气雾剂造成的致敏小鼠中，U0126对BAL液体中的细胞计数没有产生任何抑制作用。 |
|
注意事项 |
请测试所有化合物在室内的溶解度，实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的，属于正常现象。 |
|
References: [1] Satoh T, Nakatsuka D, Watanabe Y, et al. Neuroprotection by MAPK/ERK kinase inhibition with U0126 against oxidative stress in a mouse neuronal cell line and rat primary cultured cortical neurons. Neuroscience letters, 2000, 288(2): 163-166. [2] Duan W, Chan J H P, Wong C H, et al. Anti-inflammatory effects of mitogen-activated protein kinase kinase inhibitor U0126 in an asthma mouse model. The Journal of Immunology, 2004, 172(11): 7053-7059. |
|
| 描述 | U0126-EtOH是一种高选择性的MEK1/2抑制剂，IC50值为0.07 μM/0.06 μM，对ΔN3-S218E/S222D MEK的亲和性比PD98059高100倍。 | |||||
| 靶点 | MEK1 | MEK2 | ||||
| IC50 | 0.07 μM | 0.06 μM | ||||
质量控制和MSDS
- 批次:
化学结构
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