KY-226

KY-226 (CAS No.: 1621673-53-7) is a potent, selective, and orally active allosteric inhibitor of protein tyrosine phosphatase 1B (PTP1B), a key negative regulator of insulin and leptin signaling pathways, positioning it as a valuable small-molecule tool for metabolic disease and neuroprotection research. KY-226 exhibits inhibitory activity in the low micromolar to submicromolar range and enhances insulin receptor phosphorylation in hepatocellular models such as HepG2 cells, reflecting its ability to potentiate insulin signaling. Mechanistically, it modulates downstream pathways including Akt, ERK, and STAT3, thereby influencing glucose homeostasis, lipid metabolism, and energy balance, while lacking detectable PPARγ agonist activity. In vivo studies demonstrate that KY-226 improves glycemic control, reduces triglyceride and hemoglobin A1c levels, and attenuates diet-induced obesity phenotypes, effects associated with enhanced insulin and leptin signaling. Additionally, KY-226 displays neuroprotective properties in models of cerebral ischemia, where it restores Akt phosphorylation, reduces oxidative stress, and supports blood-brain barrier integrity via pathways such as Akt/FoxO1. This compound is widely used in cell-based assays and animal models to investigate metabolic regulation, signal transduction, and ischemic injury, with experimental concentrations or dosing regimens typically tailored to specific study designs in pharmacological and translational research contexts.