U0126-EtOH
U0126-EtOH is a selective inhibitor of MEK1 and MEK2 with IC50 values of 70 nM and 60 nM, resepctively [1].
U0126 was screened out as an anti-inflammatory agent that inhibited AP-1 transcription with IC50 value of 1μM and had no interactions with GREs. U0126 binds MEK1/2 in a unique site. This inhibition of MEK1/2 is noncompetitive with ERK and ATP. U0126 showed no effects on other MAPKKs. In HT22 cells, U0126 treatment significantly inhibited the cell injury caused by oxidative glutamate toxicity and remarkably blocked the phosphorylation of ERK1/2. Besides that, U0126 exerted no neuroprotection against other stimuli such as TNFα and actinomycin D. U0126 treatment also protected the primary cultured cortical neurons from oxidative glutamate toxicity and hypoxia/reoxygenation [1, 2].
References:
[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.
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| 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 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment: [1] | |
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Cell lines |
HT22 cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37°C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
10 μM, 24 hours |
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Applications |
Cells were exposed to 5 mM glutamate with or without different concentrations of the inhibitor. The viability of HT22 cells was determined by MTT assay 24 h after the treatment. The results showed that U0126 inhibited cell death induced by glutamate toxicity dose-dependently. The complete inhibition of cell injury was achieved at 10 μM, a concentration that specifically inhibits MEK1/2. |
| Animal experiment: [2] | |
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Animal models |
Male BALB/c mice |
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Dosage form |
Intraperitoneal injection; 7.5, 15 and 30 mg/kg |
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Applications |
Mice were sensitized by i.p. injections of 20 μg of OVA and 4 mg of Al(OH)3. BAL fluid was collected 24 h after the last OVA aerosol challenge. U0126 (7.5, 15, and 30 mg/kg) substantially reduced the total cell number recovered in BAL fluid as compared with PEG control, which was mainly due to a significant reduction in eosinophils in the U0126-treated mice in a dose-dependent manner. U0126 did not show any inhibitory effects on BAL fluid cell counts from sensitized mice challenged with saline aerosol. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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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. |
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| Description | U0126-EtOH is a highly selective inhibitor of MEK1/2 with IC50 of 0.07 μM/0.06 μM, 100-fold higher affinity for ΔN3-S218E/S222D MEK than PD98059. | |||||
| Targets | MEK1 | MEK2 | ||||
| IC50 | 0.07 μM | 0.06 μM | ||||
Quality Control & MSDS
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