| Description |
AS1842856 is a potent and cell-permeable Foxo1 inhibitor with an IC50 of 30 nM.
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| Related Catalog |
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| Target |
IC50: 30 nM (Foxo1)[1]
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| In Vitro |
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].
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| In Vivo |
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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| Cell Assay |
Rat hepatoma Fao cells are cultured in DMEM with 5.5 mM glucose and 10% FBS. Glucose production rate is measured using glucose CII-test reagent. In brief, after 18 h of treatment with either insulin or AS1842856 at the indicated concentrations, the cells are ished three times with PBS. The cells are then incubated for 3 h at 37°C in 5% CO2 in a glucose production buffer (glucose-free DMEM, pH 7.4, containing 20 mM sodium pyruvate, without phenol red)[1].
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| Animal Admin |
AS1842856 is dissolved in 6% cyclodextrin for oral administration. Pyruvate or glucose tolerance tests are performed in male mice aged 7 to 9 weeks. Mice are orally administered either AS1842856 dissolved in 6% cyclodextrin or vehicle (6% cyclodextrin only) at three time points (8 AM, 6 PM, and 8 AM on the second day). Food is removed after initial dosing and withheld throughout the study (26-h fasting)[1].
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| References |
[1]. Nagashima T, et al. Discovery of novel forkhead box O1 inhibitors for treating type 2 diabetes: improvement of fasting glycemia in diabetic db/db mice. Mol Pharmacol. 2010 Nov;78(5):961-70.
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