U0126-EtOH

U0126-EtOH (U0126 Ethanol) 是一种非 ATP 竞争性的选择性MEK1和MEK2抑制剂,IC50分别为 72 nM 和 58 nM。U0126-EtOH 可抑制自噬。

CAS号

1173097-76-1

分子式

C18H16N6S2·C2H6O

主要靶点

MEK|Autophagy|Mitophagy|Influenza Virus

仅限科研使用

Cat No : CM05075

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Synonyms

U0126 Ethanol|U0126



产品信息

U0126-EtOH is a non-ATP competitive specific inhibitor of MEK1/2 (IC50: 0.07/0.06 μM).

CAS号 1173097-76-1
分子式 C18H16N6S2·C2H6O
主要靶点 MEK|Autophagy|Mitophagy|Influenza Virus
主要通路 自噬|MAPK信号通路|微生物学
分子量 426.6
纯度 98.65%, 此纯度可做参考,具体纯度与批次有关系,可咨询客服
储存条件 Powder: -20°C for 3 years | In solvent: -80°C for 1 year
别名 U0126 Ethanol|U0126

靶点活性

MEK1:70 nM (cell free)|MEK2:60 nM (cell free)

体内活性

Treatment of mice with U0126 via the aerosol route led to (i) inhibition of MEK activation in the lung (ii) reduction of progeny IAV titers compared to untreated controls (iii) protection of IAV infected mice against a 100× lethal viral challenge [4]. In all U0126 (10.5 mg/kg) experiments, engraftment and early tumor growth were significantly decreased. Furthermore, a 60–70% reduction in the volume of tumors treated with U0126 was obtained 9 days after injection and thereafter. Cdk1 expression was also strongly reduced in U0126-treated mice [5].

体外活性

U0126 antagonized AP-1 transcriptional activity via noncompetitive inhibition of the dual specificity kinase MEK with an IC50 of 0.07 microM for MEK 1 and 0.06 microM for MEK 2 [1]. In fibroblasts treated with TPA/serum, U0126 suppressed the up-regulation of c-Fos and c-Jun proteins by 50–80%. Treatment with 10 μM U0126 did not affect the protein levels of the constitutively expressed transcription factors SP-1 or JunD and Fra-1 [2]. U0126 caused phosphorylation and activation of AMPK) and increased phosphorylation of its downstream target acetyl-CoA carboxylase, in HEK293 cells. This effect only occurred in cells expressing the upstream kinase, LKB1 [3].

溶解度

Ethanol:<1 mg/mL,DMSO:79 mg/mL (185.2 mM)

细胞实验

HEK293 cells were maintained in Dulbecco's modification of Eagle's medium (low glucose) plus 10% foetal bovine serum. HeLa cells stably expressing wild type or kinase-dead LKB1 have been described. AMPK activity was determined by immunoprecipitate kinase assays using anti-AMPK-a1 and -a2 antibodies. Antibodies recognising AMPK phosphorylated on Thr-172 (anti-pT172), AMPK-α1 and -α2 and acetyl-CoA carboxylase-1 (ACC1) phosphorylated on Ser-80 [16] were described previously. Quantification of ratios of signals from phosphorylated and total protein using these antibodies was performed by dual labelling using the LI-COR Odyssey IR imager as described. Contents of ATP and ADP were determined for cells in 6 cm culture dishes by quickly pouring off the medium, adding 350 μl of ice-cold 5% perchloric acid, scraping the cells off with a plastic scraper, and centrifuging (14 000 · g; 3 min, 4 °C) to remove insoluble material. The perchloric acid was then extracted from the supernatant and nucleotides analysed by capillary electrophoresis of perchloric acid extracts as described previously. All incubations of cells were performed in triplicate and results are expressed as means ± S.E.M [3].

动物实验

Prior to injection, FI cells were labeled with a stable fluorescent dye molecule, DiA at 10 μg/ml for 5 h at 37 1C. After washing to remove free DiA, cells were trypsinized for inoculation (U0126 experiments) or transfection (RNAi experiments). Biliary epithelial cells were injected subcutaneously, at the indicated times, into the tibia of nude mice. In the chemical experiments, 3h after inoculation, mice were treated with U0126 (10.5 mg/kg) daily by intraperitoneal injection. The length and width of each tumor were measured every day by using a caliper. The following formula was used to calculate tumor volumes ? width2 length/2. Mice were killed at the end of experiment. Tumors were immediately frozen in liquid nitrogen [5].

参考文献

1.Duncia JV, et al. MEK inhibitors: the chemistry and biological activity of U0126, its analogs, and cyclization products. Bioorg Med Chem Lett. 1998, 8(20), 2839-2844.
2.Zhou B, Yan J, Guo L, et al. Hepatoma cell-intrinsic TLR9 activation induces immune escape through PD-L1 upregulation in hepatocellular carcinoma[J]. Theranostics. 2020, 10(14): 6530.
3.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.
4.Dokladda K, et al. PD98059 and U0126 activate AMP-activated protein kinase by increasing the cellular AMP:ATP ratio and not via inhibition of the MAP kinase pathway. FEBS Lett. 2005 Jan 3;579(1):236-40.
5.Droebner K, et al. Antiviral activity of the MEK-inhibitor U0126 against pandemic H1N1v and highly pathogenic avian influenza virus in vitro and in vivo. Antiviral Res. 2011 Nov;92(2):195-203.
6.Bessard A, et al. RNAi-mediated ERK2 knockdown inhibits growth of tumor cells in vitro and in vivo. Oncogene. 2008 Sep 11;27(40):5315-25.
7.Ahnstedt H, et al. U0126 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.
8.Zeng H, Pathak J L, Shi Y, et al. Indirect selective laser sintering-printed microporous biphasic calcium phosphate scaffold promotes endogenous bone regeneration via activation of ERK1/2 signaling[J]. Biofabrication. 2020, 12(2): 025032.
9.Shao S, Xia H, Hu M, et al. Isotalatizidine, a C 19-diterpenoid alkaloid, attenuates chronic neuropathic pain through stimulating ERK/CREB signaling pathway-mediated microglial dynorphin A expression[J]. Journal of Neuroinflammation. 2020, 17(1): 1-11.
10.Zeng H, Pathak J L, Shi Y, et al. Indirect selective laser sintering printed microporous biphasic calcium phosphate scaffold promotes endogenous bone regeneration via activation of ERK1/2 signaling[J]. Biofabrication. 2020.

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