AS1708727

AS1708727 is an orally active Foxo1 inhibitor, with EC50 values of 0.33 μM and 0.59 μM for G6Pase and PEPCK, respectively[1].

Research Areas >> Cancer

Signaling Pathways >> Others >> Others

Research Areas >> Metabolic Disease

AS1708727 suppresses increases in blood glucose level by inhibiting gluconeogenic gene expression[1]. RT-PCR[1] Cell Line: Fao cells, derived from the H4IIE hepatoma cell line. Concentration: 0.1-3000 μM. Incubation Time: 18 h. Result: Showed dose-dependent reduction in mRNA levels for G6Pase and PEPCK.

AS1708727 (30 to 300 mg/kg, orally) reduces both blood glucose and triglyceride levels, exhibiting anti-diabetic effects[1]. Animal Model: db/db mice aged six weeks[1]. Dosage: 100-1000 mg/kg (Pharmacokinetic Analysis). Administration: Orally. Result: Cmax) was 26.7 μM and maximum drug concentration time (Tmax) of 0.5 h at 300 mg/kg[1]. Liver concentration of AS1708727 at 0.5-2 h after oral administration was 3.7- to 5.4-fold higher than the plasma concentration, indicating good liver transition of AS1708727[1]. Animal Model: Diabetic model mice[1]. Dosage: 30 to 300 mg/kg. Administration: Orally twice daily for 4 days. Result: Blood glucose level was significantly reduced at 300 mg/kg[1]. Plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were significantly reduced at 300 mg/kg[1]. G6Pase and PEPCK mRNA levels were significantly reduced at dosages of 100 and 300 mg/kg[1].

[1]. Hirotsugu Tanaka, et al. Effects of the Novel Foxo1 Inhibitor AS1708727 on Plasma Glucose and Triglyceride Levels in Diabetic Db/Db Mice. Eur J Pharmacol. 2010 Oct 25;645(1-3):185-91.