AS1842856 是一种特异性的FOXO1抑制剂，IC50为 30 nM。它抑制自噬，直接与 FOXO1 结合而降低 FOXO1 的活性。

AS1842856, a cell-permeable inhibitor, can block the transcription activity of Foxo1 (IC50: 33 nM). It can directly bind to the active Foxo1, but not the Ser256-phosphorylated form.

AS1842856 predominantly suppresses Foxo1-mediated transactivation by directly binding to Foxo1. In HepG2 cells transiently transfected with a Foxo1 expression vector, AS1842856 potently represses Foxo1-mediated promoter activity in a dose-dependent manner similar to that seen in insulin treatment.AS1842856 administered at 0.1 μM inhibits Foxo3a- and Foxo4-mediated promoter activity by 3 and 20%, respectively. In contrast, Foxo1-mediated promoter activity is decreased by 70%. Foxo1 inhibitor AS1842856 may suppress endogenous G6Pase and PEPCK activities by decreasing their mRNA levels, which may lead to inhibition of glucose production in Fao cells[1].

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 while administration to normal mice does not affect 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].

Fao cells are serum-starved (1 h) and incubated for 30 min with either insulin or AS1842856 at the indicated concentration. Protein lysates are prepared from cells treated with either insulin or AS1842856, and relative concentration of phosphorylated Foxo1 protein is determined by Western blot analysis. (Only for Reference)

836620-48-5

C18H22FN3O3

347.39

H2O:<1 mgml
DMSO:7 mg/mL(20.2 mM)
Ethanol:<1 mgml
Powder: -20°C for 3 years
In solvent: -80°C for 2 years