In vitro, mitapivat ameliorates the metabolic and proteomic profiles of human β-thal erythroblasts, associated with decreased overall cysteine oxidation and downregulation of HSP70 expression. PK isoforms PKLR (A) and PKM (all proteoforms) (B) in β-thal erythroblasts as a function of mitapivat treatment. (C) Top 50 proteins (by t test) affected by mitapivat treatment in β-thal erythroblasts (see also supplemental Figure 9). (D) The heat map shows the metabolites that were significantly (t test) affected by mitapivat treatment of β-thal erythroblasts. (E) A detail of ATP, increasing significantly upon mitapivat treatment. (F) Overview of adenylate pools and glycolysis (group averages) in β-thal erythroblasts in the presence or absence of mitapivat (blue vs red indicates low vs high). (G) Elevated ATP values in the mitapivat-treated group corresponded to significant elevation in overall protein phosphorylation. (H) Heat map of the top 50 cysteine redox modifications in β-thal erythroblasts upon mitapivat treatment shows a significant decrease in overall oxidation (orange), deoxidation (red), and cysàdehydroalanine (magenta) in the treated group.