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AS1842856, a specific Foxo1 inhibitor (IC50=30 nM), potently suppresses autophagy[1]. AS1842856 inhibits FoxO1 activity by suppressing the expression of SIRT1. AS1842856 only reduces the activity of FoxO1 by binding with it, without affecting its transcription and protein expression[2].

AS1842856 potently inhibits human Foxo1 transactivation and reduces glucose production through the inhibition of glucose-6 phosphatase and phosphoenolpyruvate carboxykinase mRNA levels in a rat hepatic cell line[1]. After AS1842856 treatment, there is no significant difference in the protein expression of p-FoxO1 and FoxO1 compared with the control group, but the expression of p-Akt is decreased compared with the control group[2].

Oral administration of AS1842856 to diabetic db/db mice leads to a drastic decrease in fasting plasma glucose level via the inhibition of hepatic gluconeogenic genes, whereas administration to normal mice has no effect on the fasting plasma glucose level. Treatment with AS1842856 also suppresses an increase in plasma glucose level caused by pyruvate injection in both normal and db/db mice[1].

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