Mitapivat CAS# 1260075-17-9 PKR抑制剂(MITAPIVAT)

Mitapivat (AG-348) is an oral, allosteric activator of red blood cell pyruvate kinase (PKR). In preclinical biochemical assays, it increased PKR activity with an EC50 of ~0.5 µM and stabilized the tetrameric active conformation of the enzyme. In erythroid cells from patients with pyruvate kinase deficiency, mitapivat enhanced glycolytic flux, elevated ATP production, and reduced 2,3-DPG levels. In mouse models, oral dosing increased red blood cell ATP, improved lifespan of erythrocytes, and mitigated hemolytic anemia. Pharmacokinetic studies showed good oral bioavailability and dose-dependent plasma exposure. These findings supported mitapivat’s development as the first disease-modifying therapy for PK deficiency.