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Purity: ≥98%
U0126-EtOH is a novel, selective and non-ATP competitive MEK1/2 inhibitor with potential anticviral activity. In cell-free assays, it inhibits MEK1/2 with IC50 values of 0.07 μM/0.06 μM.
| Targets |
MEK2 (IC50 = 60 nM); MEK1 (IC50 = 70 nM)
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|---|---|
| ln Vitro |
U0126-EtOH blocks the production of numerous cytokines and metalloproteinases involved in the inflammatory response by functionally antagonistic AP-1 transcriptional activity.[1] By decreasing IL-2 mRNA levels, U0126-EtOH reduces T cell proliferation in response to antigenic stimulation or cross-linked anti-CD3 plus anti-CD28 Abs without affecting proliferation brought on by IL-2.[2] According to a recent study, U0126-EtOH inhibits mitochondrial function, switches castration-resistant human prostate cancer C4-2 cells to aerobic glycolysis without the help of MEK, and counteracts resveratrol's induction of apoptosis.[3]
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| ln Vivo |
U0126-EtOH exhibits antiviral activity by stifling the spread of the 2009 pandemic IV H1N1 variant and highly pathogenic avian influenza viruses (HPAIV) in vivo in the mouse lung by inhibiting the intracellular Raf/MEK/ERK signaling pathway.[4] By activating nuclear respiratory factor 1, mitochondrial transcription factor A, and peroxisome proliferator-activated receptor gamma coactivator-1a in A-injected rats, U0126-EtOH demonstrates the potential neuroprotective effect and improving spatial learning in the Morris water maze (MWM).[5]
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| Enzyme Assay |
In these assays, the amount of immunoprecipitated wild type MEK is adjusted to produce an equivalent number of activity units to that of 10 nM recombinant MEK. A 96-well nitrocellulose filter apparatus is used to measure reaction velocities, as detailed below. A 10 nM enzyme concentration, 20 mM Hepes, 10 mM MgCl2, 5 mM β-mercaptoethanol, 0.1 mg/mL BSA, pH 7.4, and room temperature are used for all reactions unless otherwise specified. The pre-mixed MEK/ERK/inhibitor reaction mixture is added [γ-33P]ATP to start the reactions. An aliquot of 100 μL is then taken every 6 minutes and transferred to the 96-well nitrocellulose membrane plate containing 50 mM EDTA to stop the reaction. The membrane plate is drawn and vacuum-washed four times with buffer. After that, 30 μL of Microscint-20 scintillation fluid is poured into the wells, and a Top Count scintillation counter is used to measure the radioactivity of 33P-phosphorylated ERK. From the slopes of radioactivity versus time plots, speeds are calculated. Unless otherwise stated, ERK and ATP concentrations are 400 nM and 40 μM, respectively. The initial reaction velocities in the presence and absence of the inhibitor, respectively, are called Vi and Vo, and they are used to calculate the percent inhibition for all in vitro enzyme assays. The data are then plotted as a function of inhibitor concentration as a function of percent inhibition, and the IC50 is calculated by fitting the data using nonlinear least squares regression to the equation for a Langmuir isotherm. According to the information provided, rather than active site titration, enzyme concentrations are based on the molecular weights and mass of the protein used in the final assay volume. As a result, the actual concentration of the enzyme active site may vary from the reported value.
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| Cell Assay |
A.E7 or Th17 cells are incubated with B10.BR or BALB/c splenocytes that have been treated with mitomycin C, along with varying concentrations of pigeon cytochrome c, PR8 Ag, or 5 U/mL human rIL-2. In order to ascertain the direct effects of MEK inhibition on T cell proliferation, some assays also contain U0126 or an inactive analog, U0124. Each well receives a 1-µCi [3H]TdR pulse two days after culture initiation, and the following day, the cultures are harvested. Without the use of liquid scintillation mixtures, the incorporation of [3H]TdR into DNA is measured on a Packard Matrix 96 direct beta counter.
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| Animal Protocol |
Female C57Bl/6 mice infected by Mouse-adapted highly pathogenic avian influenza A/FPV/Bratislava/79 (H7N7; FPV) virus and swine origin human influenza A virus (SOIV) A/Regensburg/D6/2009 (H1N1v; RB1).
≤10 mM Administered via aerosol. |
| References |
| Molecular Formula |
C18H16N6S2.C2H6O
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|---|---|
| Molecular Weight |
426.56
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| Exact Mass |
426.13
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| Elemental Analysis |
C, 56.32; H, 5.20; N, 19.70; O, 3.75; S, 15.03
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| CAS # |
1173097-76-1
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| Related CAS # |
U0126;109511-58-2
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| Appearance |
White to off-white solid powder
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| SMILES |
CCO.C1=CC=C(C(=C1)N)S/C(=C(/C(=C(/SC2=CC=CC=C2N)\N)/C#N)\C#N)/N
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| InChi Key |
CFQULUVMLGZVAF-OYJDLGDISA-N
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| InChi Code |
InChI=1S/C18H16N6S2.C2H6O/c19-9-11(17(23)25-15-7-3-1-5-13(15)21)12(10-20)18(24)26-16-8-4-2-6-14(16)22;1-2-3/h1-8H,21-24H2;3H,2H2,1H3/b17-11+,18-12+
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| Chemical Name |
(2Z,3Z)-2,3-bis[amino-(2-aminophenyl)sulfanylmethylidene]butanedinitrile;ethanol
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| Synonyms |
U0126; U-0126-EtOH; U0126 EtOH; U 0126; U-0126; U0126-EtOH; U 0126-EtOH; U 0126 EtOH; U-0126 EtOH
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.88 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.88 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.88 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 10% DMSO+50% PEG 300+ddH2O: 28mg/mL Solubility in Formulation 5: 5 mg/mL (11.72 mM) in 0.5% CMC-Na/saline water (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 Increased endothelin type B (ETB) receptor-mediated vasoconstriction and p-ERK1/2 expression in female rat MCAs.J Cereb Blood Flow Metab.2015 Mar;35(3):454-60. |
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 Ischemia-induced increase in smooth muscle endothelin type B (ETB) receptor and p-ERK1/2 expression after transient middle cerebral artery occlusion (tMCAO) is prevented by U0126 treatment. (A) Representative images of ETBreceptor and (B) p-ERK1/2 expression at 48 hours of reperfusion after tMCAO in the occluded and non-occluded middle cerebral artery (MCA) in untreated, vehicle, and U0126 animals. Scale bar: 50 μm. (C) Quantification (mean fluorescence intensity in the smooth muscle cell layer of the occluded MCA normalized to the non-occluded MCA) of ETBreceptor and (D) p-ERK1/2 expression.J Cereb Blood Flow Metab.2015 Mar;35(3):454-60. |
 MEK1/2 inhibition results in improved neurologic function after transient middle cerebral artery occlusion (tMCAO). (A) Infarct volume from untreated (n=7), vehicle (n=4), and U0126-treated (n=9) rats at 48 hours of reperfusion after tMCAO. (B) Representative NeuN immunostaining of brain slices from Bregma −2.2 to +3.8 is shown (1 mm interval). The border between nonlesioned (NeuN positive) and lesioned areas is depicted in the untreated group. (C) Recovery of sensorimotor function up to 14 days after tMCAO with the 28-point neuroscore. (D) Gross neurologic function graded in six levels from 0—no visible defects to 5—death.J Cereb Blood Flow Metab.2015 Mar;35(3):454-60. |
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Experimental design.J Cereb Blood Flow Metab.2015 Mar;35(3):454-60. |
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