MK-0599

MK-0599 is an orally active, potent, and specific small-molecule allosteric activator of glucokinase (GK) that was developed by Merck for the treatment of type 2 diabetes. Glucokinase serves as a key glucose sensor in pancreatic beta-cells, where it regulates glucose-stimulated insulin secretion, and in hepatocytes, where it facilitates glucose uptake and glycogen synthesis. By allosterically activating glucokinase, MK-0599 enhances hepatic glucose metabolism and potentiates insulin secretion in a glucose-dependent manner. Although MK-0599 demonstrated significant glucose-lowering efficacy in Phase 1 clinical trials in healthy normoglycemic subjects, its clinical development was subsequently discontinued.