KY-226 is a potent inhibitor of protein tyrosine phosphatase 1B (PTP1B)(IC50: 0.25 μM,)

In db/db mice, the oral administration of KY-226 (10 and 30 mg/kg/day, 4 weeks) significantly reduced plasma glucose and triglyceride levels as well as hemoglobin A1c values without increasing body weight gain, while pioglitazone exerted similar effects with increases in body weight gain.?KY-226 attenuated plasma glucose elevations in the oral glucose tolerance test.?KY-226 also increased pIR and phosphorylated Akt in the liver and femoral muscle.?In high-fat diet-induced obese mice, the oral administration of KY-226 (30 and 60 mg/kg/day, 4 weeks) decreased body weight gain, food consumption, and fat volume gain with increases in phosphorylated STAT3 in the hypothalamus.