YH-GKA

YH-GKA is a novel benzamide-derived small molecule glucokinase activator (GKA) developed by Yuhan for the treatment of type 2 diabetes mellitus. It functions through a dual mechanism: enhancing glucose uptake in the liver and stimulating insulin secretion from pancreatic beta cells by increasing the activity of glucokinase, the rate-limiting enzyme in glucose metabolism. Preclinical studies in mouse models (C57BL/J6 and ob/ob) have shown that YH-GKA effectively reduces blood glucose levels with efficacy comparable to metformin, while maintaining high bioavailability and a favorable safety profile regarding body weight and lipid levels. Furthermore, YH-GKA demonstrates cytoprotective effects on pancreatic beta cells, promoting proliferation and preventing apoptosis induced by glucotoxicity through the activation of the IRS-2/AKT signaling pathway and the improvement of mitochondrial function.