KY-226 is a selective allosteric protein tyrosine phosphatase 1B (PTP1B) inhibitor (IC50 = 250 nM) with no activity at PPARgamma.1 It significantly reduced plasma glucose, triglyceride, and A1c levels without weight gain in db/db mice.2 It has been suggested that KY-226s anti-diabetic effects occur via enhancements in insulin signaling and anti-obesity effects via leptin signaling enhancements.2 KY-226 has also been shown to protect neurons from cerebral ischemia.3 This effect is mediated by restoration of tight junction proteins via activation of the Akt/FoxO1 pathway.4
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