Mitapivat (AG-348) functions as an orally active allosteric activator of pyruvate kinase. It enhances enzymatic activity, protein stability, and ATP levels across various PKLR genotypes, indicating its potential in restoring the function of PK (pyruvate kinase)-deficient glycolytic pathways. Mitapivat is applicable in the investigation of PK deficiency [1][2][3].
体内研究
Mitapivat (50 mg/kg; p.o.; twice daily for 21 days) ameliorates anemia in a mouse model of β-thalassemia [2].
体外研究
Mitapivat (0.1 nM-100 μM; 16 h) stimulates WT PK-R in red blood cells from healthy donors [1].
Mitapivat (0.01 nM-10 μM; 16 h) enhances ATP production in RBCs in a dose-dependent manner [1].
Mitapivat 细胞实验
Cell Line
Concentration
Treated Time
Description
References
red blood cells
2 μM
50 minutes
To evaluate the effect of Mitapivat on erythroid vesicle release from RBCs, results showed Mitapivat significantly reduced the release of erythroid vesicles and normalized the protein composition of released vesicles.
JCI Insight. 2023 Oct 23;8(20):e172656
Mitapivat 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Hbbth3/+ mouse model
Oral
50 mg/kg
Twice daily for 21 days
Mitapivat ameliorated ineffective erythropoiesis and anemia in Hbbth3/+ mice, increased ATP levels, reduced reactive oxygen species production, and improved mitochondrial dysfunction.
J Clin Invest. 2021 May 17;131(10):e144206
Mice
Β-thalassemia mouse model
Oral gavage
50 mg/kg
Twice daily for 10 days
Mitapivat improved transfusion burden and reduced iron overload in β-thal mice, decreased iron accumulation in spleen and liver, and ameliorated ineffective erythropoiesis.
Haematologica. 2023 Sep 1;108(9):2535-2541
Mice
Mouse model of hereditary spherocytosis
Oral
100 mg/kg/d
Once daily for 6 months
To assess the effect of Mitapivat on anemia and RBC metabolism, results showed Mitapivat significantly improved anemia, reprogrammed the RBC metabolome, and reduced spleen iron content and liver iron overload.
JCI Insight. 2023 Oct 23;8(20):e172656
Mice
Townes SCD mouse model
Oral
200 mg/kg/day
Once daily for 4 weeks
Mitapivat further increased ATP without significantly changing 2,3-DPG or hemoglobin levels, and decreased levels of leukocytosis, erythrocyte oxidative stress, and the percentage of erythrocytes that retained mitochondria in HbSS mice.
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