KY-226

KY-226 is a potent, selective, orally active and allosteric protein tyrosine phosphatase 1B (PTP1B) inhibitor with an IC₅₀ of 0.25 μM, and without PPARγ agonist activity. KY-226 exerts anti-diabetic and anti-obesity effects by enhancing insulin and leptin signaling, respectively. KY-226 also protects neurons from cerebral ischemic injury^[1][2]. IC50 & Target: IC50: 0.25 μM (Protein tyrosine phosphatase 1B (PTP1B))^[2] In Vitro: In human hepatoma-derived cells (HepG2), KY-226 (0.3-10 μM) increases the phosphorylated insulin receptor (pIR) produced by insulin^[1].
KY-226 (1 μM; 24 hours; bEnd.3 cells) treatment rescues lipopolysaccharide-induced reduction of mRNA and protein levels of ZO-1. KY-226 treatment restores phosphorylation of pAkt (T308) and its downstream target forkhead box protein O1 (FoxO1) (S256) in bEnd.3 cells^[2]. In Vivo: KY-226 (10-30 mg/kg/day; oral administration; daily; for 4 weeks; male db/db mice) treatment significantly reduces plasma glucose and triglyceride levels as well as hemoglobin A1c values without increasing body weight gain^[1].
KY-226 attenuates plasma glucose elevations in the oral glucose tolerance test. KY-226 also increases pIR and phosphorylated Akt in the liver and femoral muscle^[1].