YLF-466D is an orally bioavailable activator of AMP-activated protein kinase (AMPK), an enzyme involved in regulation of cellular energy homeostasis. YLF-466D activates AMPK at a concentration of 150 µM in platelets. It inhibits platelet aggregation induced by thrombin, ADP, and collagen (IC50s = 84, 55, and 87 µM, respectively) and inhibits aggregation of whole blood. YLF-466D leads to dose-dependent glucose uptake in L6 myotubes and, at a dose of 150 mg/kg, improves glucose tolerance in two mouse models of diabetes.