Potent AMPK activator. AICAR activates AMPK due to increased phosphorylation, causes phosphorylation and inactivation of HMG-CoA reductase, and almost total cessation of fatty acid and sterol synthesis. AICAR causes ZMP (a cellular mimetic of AMP) to accumulate inside the cell but does not perturb the cellular contents of ATP, ADP or AMP, and induces differentiation of acute myeloid leukemia cells, and astroglial differentiation of neural stem cells via activating the JAK/STAT3 pathway independently of AMP-activated protein kinase. AICAR can also significantly up-regulate pluripotency-associated genes and down-regulate differentiation-associated transcription factors.

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