Effects of mitapivat-mediated pyruvate kinase activation in sickle cell disease. Mitapivat (AG-348) is an oral allosteric activator of pyruvate kinase (PK), a key enzyme in RBC glycolysis. PK activation decreases 2,3-DPG levels and increases ATP levels in RBCs. This study showed that mitapivat decreased parameters of hemolysis, RBC sickling and vaso-occlusive events and increased hemoglobin (Hb) level and Hb-oxygen affinity.1,3-DPG, 1,3-Disphosphoglycerate; ADP, adenosine diphosphate; P, phosphate; 2,3-DPG, 2,3-diphosphoglycerate; ATP, adenosine triphosphate; 3-PG, 3-Phosphoglycerate; PEP, phosphoenolpyruvate; RBC, red blood cell; Hb, hemoglobin.