(2Z,3Z)-U0126

(2Z,3Z)-U0126 is a selective inhibitor of MEK1 and MEK2, demonstrating potent antiinflammatory effects by noncompetitively inhibiting AP-1 transcriptional activity with IC50 values of 72 nM for MEK1 and 58 nM for MEK2. (2Z,3Z)-U0126 also inhibits anchorage-independent growth of Ki-ras-transformed rat fibroblasts by blocking both the extracellular signal-regulated kinase and mammalian target of rapamycin pathways. Additionally, (2Z,3Z)-U0126 can undergo isomerization and cyclization, resulting in various products that show reduced affinity for MEK and diminished AP-1 inhibition compared to the parent compound.