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Description: U0126 (also known as U0126-EtOH) is a novel potent, highly selective and non-ATP competitive inhibitor of MEK1/2 with IC50 of 0.07 uM/0.06 uM in cell-free assays. U0126 was found to functionally antagonize AP-1 transcriptional activity via noncompetitive inhibition of the dual specificity kinase MEK1/2. It displays 100-fold higher affinity for deltaN3-S218E/S222D MEK than PD98059. U0126-EtOH was screened out as an anti-inflammatory agent that inhibited AP-1 transcription with IC50 value of 1uM and had no interactions with GREs. In HT22 cells, U0126-EtOH treatment significantly inhibited the cell injury caused by oxidative glutamate toxicity and remarkably blocked the phosphorylation of ERK1/2. with an IC50 of 0.07 microM for MEK 1 and 0.06 microM for MEK 2. U0126 can undergo isomerization and cyclization reactions to form a variety of products, both chemically and in vivo, all of which exhibit less affinity for MEK and lower inhibition of AP-1 activity than parent, U0126.
References: Bioorg Med Chem Lett. 1998 Oct 20; 8(20):2839-44; Behav Brain Res. 2012 Jun 15; 232(1):165-73.
Related CAS: 1173097-76-1 (U0126-EtOH)
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