U0126-EtOH
(Synonyms: 2,3-双[氨基[(2-氨基苯基)硫]亚甲基]丁二腈乙醇盐) 目录号 : GC12807
U0126-EtOH-EtOH (U0126) 作为一种非 ATP 竞争性和选择性抑制剂，对 MEK1 和 MEK2 具有有效抑制作用，IC50 分别为 72 nM 和 58 nM。
Cas No.:1173097-76-1
Sample solution is provided at 25 µL, 10mM.
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Related Biological Data
Periostin activates the MAPK signaling pathway to promote extracellular matrix degradation, stemness, and chemoresistance in TNBCs.g–h. qPCR analysis of the indicated gene expression in MDA–MB–231 cells treated with IgG or rhperiostin and/or U0126–EtOH for 24 h.
qPCR analysis of the indicated gene expression in MDA–MB–231 cells treated with IgG or rhperiostin and/or U0126–EtOH(GlpBio) for 24 h.
Lipids Health Dis 22.1 (2023): 1-14. PMID: 37716956 IF: 4.5003 -
Related Biological Data
Effects of AS-IV on MAPKs and NF-κB activation.Cells were pre-incubated with 10 μM U0126, 10 μM SB203580, or 30 μM AS-IV for 4 h and then treated with 1 μM Fe2+ for 24 h. Western blots were used to quantify the expression of nuclear NF-κB (I and J) in cells.
U0126 + Fe2+ cells: pretreated with 10 μM U0126(GlpBio) for 4 h before incubation with 1 μM Fe2+ for 24 h.
Toxicol Appl Pharm (2020): 115361. PMID: 33285147 IF: 4.211
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
Fibroblast-like synoviocytes(FLSs) |
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Preparation Method |
FLSs were plated at a density of 5 × 104 mL−1 in 6-well plates for 24 h. FLSs were serum starved for 24 h before incubation with Cyclopamine (10 μM) or Purmorphamine (1 μM), or co-treated with U0126-EtOH-EtOH (10 μM) Purmorphamine (1 μM). Cell counting kit-8 assay was performed to examine the cell viability. |
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Reaction Conditions |
10 μM; 48 h |
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Applications |
U0126-EtOH-EtOH inhibit cell viability and regulate cell cycle distribution of RA-FLSs induced by SHH signaling. |
| Animal experiment [2]: | |
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Animal models |
Rats |
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Preparation Method |
Rats were subjected to 120 minutes tMCAO and thereafter treated with the MEK1/2 inhibitor U0126-EtOH (30 mg/kg intraperitoneally) at 0 and 24 hours of reperfusion. |
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Dosage form |
30 mg/kg; i.p. |
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Applications |
After treatment with U0126-EtOH, the vasoconstriction to S6c was markedly reduced. ET-1-induced vasoconstriction was not significantly different in non-occluded and occluded MCAs, and not affected by U0126-EtOH. |
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References: [1]. Liu F, et al. Sonic Hedgehog Signaling Pathway Mediates Proliferation and Migration of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via MAPK/ERK Signaling Pathway. Front Immunol. 2018 Dec 5;9:2847. [2]. Ahnstedt H, et al. U0126-EtOH attenuates cerebral vasoconstriction and improves long-term neurologic outcome after stroke in female rats. J Cereb Blood Flow Metab. 2015 Mar;35(3):454-60. |
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U0126-EtOH-EtOH (U0126), as a non-ATP competitive and selective inhibitor, a has potent inhibition on MEK1 and MEK2 with IC50s of 72 nM and 58 nM, respectively.[1][6]
In vitro experiment it shown that treatment with 10 μM of U0126-EtOH-EtOH decreased the numbers of migration RA-FLSs induced by Sonic Hedgehog signaling. [2] In vitro, pretreatment with 50?μM SB203580 (the p38 inhibitor) and 50?μM U0126-EtOH-EtOH (ERK1/2 inhibitor) in the microglial cells obviously brogated the effects of isotalatizidine.[3] In addition, H9C2 cells pretreated with 10μM U0126-EtOH reduced ischemia/reperfusion-induced apoptosis and autophagy in myocardium and reduced cisplatin-induced renal injury by decreasing inflammation and apoptosis by inhibition of ERK1/2 phosphorylation.[4] Pretreatment with 10 μM of U0126-EtOH protected PC-12 Cells against hydrogen peroxide-induced cell death independent of MEK inhibition.[6] Moreover, at 1 μM to 20 μM of U0126-EtOH increased the half-width and decay time of action potential in a dose-dependent manner in primary hippocampal neurons. Bath application of 40?μM U0126-EtOH is more potent than 4-AP and TEA in suppressing maximal firing rate of pyramidal neurons in hippocampal slices.[5]
In vivo efficacy test it demonstrated that pretreatment with 1mg/kg U0126-EtOH in in STZ-induced diabetic mice improved cardiac function and ameliorated cardiac hypertrophy.[4] In the acute phase of experimental stroke, 30 mg/kg U0126-EtOH prevent activation of MMP-9, additionly, by adding U0126-EtOH in combination with rt-PA prevent activation of MMP-9 expression leading to BBB leakage and hemorrhagic transformation.[6]
References:
[1]. Favata MF, et al. Identification of a novel inhibitor of mitogen-activated protein kinase kinase. J Biol Chem. 1998 Jul 17;273(29):18623-32.
[2]. Liu F, et al. Sonic Hedgehog Signaling Pathway Mediates Proliferation and Migration of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via MAPK/ERK Signaling Pathway. Front Immunol. 2018 Dec 5;9:2847.
[3]. Shao S, et al. Isotalatizidine, a C19-diterpenoid alkaloid, attenuates chronic neuropathic pain through stimulating ERK/CREB signaling pathway-mediated microglial dynorphin A expression. J Neuroinflammation. 2020 Jan 10;17(1):13.
[4]. Wang T, et al. The MEK inhibitor U0126-EtOH ameliorates diabetic cardiomyopathy by restricting XBP1's phosphorylation dependent SUMOylation. Int J Biol Sci. 2021 Jul 13;17(12):2984-2999.
[5]. Orset C, et al. Combination treatment with U0126-EtOH and rt-PA prevents adverse effects of the delayed rt-PA treatment after acute ischemic stroke. Sci Rep. 2021 Jun 7;11(1):11993.
[6]. Ong Q, et al. U0126-EtOH protects cells against oxidative stress independent of its function as a MEK inhibitor. ACS Chem Neurosci. 2015 Jan 21;6(1):130-7.
[7]. Wang JZ, et al. Potent block of potassium channels by MEK inhibitor U0126-EtOH in primary cultures and brain slices. Sci Rep. 2018 Jun 11;8(1):8808.
U0126-EtOH-EtOH (U0126) 作为一种非 ATP 竞争性和选择性抑制剂，对 MEK1 和 MEK2 具有有效抑制作用，IC50 分别为 72 nM 和 58 nM。[1][6]
体外实验表明，用 10 μM U0126-EtOH-EtOH 处理可减少由 Sonic Hedgehog 信号传导诱导的迁移 RA-FLS 数量。 [2] 在体外，用 50μM SB203580（p38 抑制剂）和 50μM U0126-EtOH-EtOH（ERK1/2 抑制剂）预处理小胶质细胞明显抑制了异他嗪的作用。<sup >[3] 此外，用 10μM U0126-EtOH 预处理的 H9C2 细胞减少了心肌缺血/再灌注诱导的细胞凋亡和自噬，并通过抑制 ERK1/2 磷酸化减少炎症和细胞凋亡来减少顺铂诱导的肾损伤。 [4]用 10 μM U0126-EtOH 预处理可保护 PC-12 细胞免受过氧化氢诱导的细胞死亡，而不受 MEK 抑制的影响。[6]此外，在 1 μM 时至 20 μM U0126-EtOH 在原代海马神经元中以剂量依赖性方式增加动作电位的半宽度和衰减时间。 40μM U0126-EtOH 对海马切片中锥体神经元最大放电率的抑制比 4-AP 和 TEA 更有效。[5]
体内药效试验表明，用 1mg/kg U0126-EtOH 预处理 STZ 诱导的糖尿病小鼠可改善心脏功能并改善心脏肥大。[4] 在实验性卒中的急性期, 30 mg/kg U0126-EtOH 可防止 MMP-9 的激活，此外，通过添加 U0126-EtOH 与 rt-PA 结合可防止 MMP-9 表达的激活导致 BBB 渗漏和出血转化。[6]
| Cas No. | 1173097-76-1 | SDF | |
| 别名 | 2,3-双[氨基[(2-氨基苯基)硫]亚甲基]丁二腈乙醇盐 | ||
| 化学名 | (2Z,3Z)-2,3-bis[amino-(2-aminophenyl)sulfanylmethylidene]butanedinitrile;ethanol | ||
| Canonical SMILES | CCO.C1=CC=C(C(=C1)N)SC(=C(C#N)C(=C(N)SC2=CC=CC=C2N)C#N)N | ||
| 分子式 | C18H16N6S2.C2H6O | 分子量 | 426.56 |
| 溶解度 | 50 mg/ml in DMSO (Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3443 mL | 11.7217 mL | 23.4434 mL |
| 5 mM | 0.4689 mL | 2.3443 mL | 4.6887 mL |
| 10 mM | 0.2344 mL | 1.1722 mL | 2.3443 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。