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U0126 is a selective MAP Kinase inhibitor, displaying a preference for MEK-1 and MEK-2. It is known that U0126 binds to MEK in a noncompetitive manner compared to ATP. Studies suggest that U0126 antagonizes the transcription of AP-1, via the inhibition of MEK. In addition, U0126 has been observed to inhibit promoters containing an AP-1 response element, while in contrast having no effect on promoters that lack an AP-1 response group. U0126 is an activator of PGC-1, mtTFA and Nuclear Respiratory Factor.
Inhibition of MEK/ERK activity by specific MEK inhibitors PD98059 and U0126 rapidly causes the loss of human embryonic stem cells (hESC) pluripotency, acting as a promoter of hESC differentiation. U0126 is also useful in neuronal studies in mice since it displays inhibitory effects against oxidative stress.
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