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• 产品描述： Mitapivat (AG-348) is an orally active pyruvate kinase allosteric activator. Mitapivat increases enzymatic activity, protein stability, and ATP levels over a broad range of PKLR genotypes, shows the potential to restore the activity of PK (pyruvate kinase)-deficient glycolytic pathways. Mitapivat can be used in study of PK deficiency

• 靶点： pyruvate kinase;PKM

• 体外研究：
  Mitapivat (0.1 nM-100 µM; 16 h) activates WT PK-R in RBCs from healthy donors. Mitapivat (0.01 nM-10 µM; 16 h) promotes production of ATP in RBC cells in a dose-dependent manner. Cell Viability Assay Cell Line: RBC cells Concentration: 0.1 nM-100 µM Incubation Time: 16 h (incubate overnight) Result: Increased PK-R activity in a dose-dependent manner to ~2.5-fold of DMSO control with an AC50 of 62 nM. Cell Viability Assay Cell Line: RBC cells Concentration: 0.01 nM-10 µM Incubation Time: 16 h (incubate overnight) Result: Consistently increased ATP levels in a dose-dependent manner by an average of 60% over DMSO control with an AC50 of 10.9 nM.

• 体内研究：
  Mitapivat (50 mg/kg; p.o.; twice daily for 21 days) improves anemia in a mouse model for β-thalassemia. Animal Model: WT C57B6 and Hbbth3/+ mice (both are 2-month-old female mice; β-thalassemia model). Dosage: 50 mg/kg Administration: In animal feedings; single daily for 3 weeks. Result: Increased the expression of pyruvate kinase isoforms in both red cells and erythroid precursors from Hbbth3/+ mice.Elevated pyruvate kinase activity in cells from Hbbth3/+ mice, and markedly increased ROS level in erythrocytes.Increased the expression of PKM2 in polychromatic and orthochromatic erythroblasts of Hbbth3/+ mice. Animal Model: WT C57B6 and Hbbth3/+ mice (both are 2-month-old female mice; β-thalassemia model). Dosage: 50 mg/kg Administration: Oral gavage, twice daily for 21 days. Result: Ameliorated ineffective erythropoiesis and anemia in Hbbth3/+ mice and increased ATP, reduced ROS production, as well as reduced markers of mitochondrial dysfunction associated with improved mitochondrial clearance.

• 参考文献：
  1. Kung C, et al. AG-348 enhances pyruvate kinase activity in red blood cells from patients with pyruvate kinase deficiency. Blood. 2017 Sep 14;130(11):1347-1356. 2. Matte A, et al. The pyruvate kinase activator mitapivat reduces hemolysis and improves anemia in a β-thalassemia mouse model. J Clin Invest. 2021 May 17;131(10):e144206. 3. Rab MAE, et al. AG-348 (Mitapivat), an allosteric activator of red blood cell pyruvate kinase, increases enzymatic activity, protein stability, and ATP levels over a broad range of PKLR genotypes. Haematologica. 2021 Jan 1;106(1):238-249.

• 溶解性： Soluble  in  DMSO

• 保存条件： -20℃

• 配置溶液浓度参考：
  

  	1mg	5mg	10mg
  1 mM	2.219 ml	11.097 ml	22.195 ml
  5 mM	0.444 ml	2.219 ml	4.439 ml
  10 mM	0.222 ml	1.11 ml	2.219 ml
  50 mM	0.044 ml	0.222 ml	0.444 ml

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本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为：

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子摩尔量 (g/mol)

• pg ng μg mg g kg =
  fM pM nM μM mM M *
  nL μL mL L *