| 產(chǎn)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 |
| 靶點(diǎn)： |
pyruvate kinase;PKM |
| 體外研究： |
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. |
| 體內(nèi)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. |
| 參考文獻(xiàn)： |
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 |
| 保存條件： |
-20℃ |
| 配置溶液濃度參考： |
|
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 |
|
| 注意： |
部分產(chǎn)品我司僅能提供部分信息，我司不保證所提供信息的權(quán)威性，僅供客戶參考交流研究之用。 |
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