U0126-EtOH |
| Catalog No.GC12807 |
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.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1173097-76-1
Sample solution is provided at 25 µL, 10mM.
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.
| Cell experiment [1]: | |
|
Cell lines |
Fibroblast-like synoviocytes(FLSs) |
|
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. |
|
Reaction Conditions |
10 μM; 48 h |
|
Applications |
U0126-EtOH-EtOH inhibit cell viability and regulate cell cycle distribution of RA-FLSs induced by SHH signaling. |
| Animal experiment [2]: | |
|
Animal models |
Rats |
|
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. |
|
Dosage form |
30 mg/kg; i.p. |
|
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. |
|
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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| Cas No. | 1173097-76-1 | SDF | |
| Chemical Name | (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 | ||
| Formula | C18H16N6S2.C2H6O | M.Wt | 426.56 |
| Solubility | 50 mg/ml in DMSO (Need ultrasonic) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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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 |
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- Purity: >98.00%
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Related Biological Data
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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
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