Mitapivat (AG-348) 是一种口服有效的丙酮酸激酶 (pyruvate kinase) 变构激活剂。Mitapivat 在广泛的PKLR基因型中增加酶活性、蛋白质稳定性和 ATP 水平，具有恢复丙酮酸激酶缺乏的糖酵解途径活性的潜力。Mitapivat 可用于丙酮酸激酶缺乏症的研究。
| 生物活性 | Mitapivat (AG-348) is an orally activepyruvate kinaseallosteric activator. Mitapivat increases enzymatic activity, protein stability, and ATP levels over a broad range ofPKLRgenotypes, shows the potential to restore the activity ofPK (pyruvate kinase)-deficient glycolytic pathways. Mitapivat can be used in study ofPKdeficiency[1][2][3]. |
| IC50& Target | pyruvate kinase[1][2][3]. |
体外研究
(In Vitro) | Mitapivat (0.1 nM-100 μM; 16 h) activates WT PK-R in RBCs from healthy donors[1].
Mitapivat (0.01 nM-10 μM; 16 h) promotes production of ATP in RBC cells in a dose-dependent manner[1].
Cell Viability Assay[1] | 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 AC50of 62 nM. |
Cell Viability Assay[1] | 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 AC50of 10.9 nM. |
|
体内研究
(In Vivo) | Mitapivat (50 mg/kg; p.o.; twice daily for 21 days) improves anemia in a mouse model for β-thalassemia[2].
| Animal Model: | WT C57B6 and Hbbth3/+mice (both are 2-month-old female mice; β-thalassemia model)[2]. | | 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)[2]. | | 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. |
|
| Clinical Trial | |
| 分子量 | |
| 性状 | |
| Formula | |
| CAS 号 | |
| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
|
| 溶解性数据 | In Vitro: DMSO : 20.83 mg/mL(46.23 mM;ultrasonic and warming and heat to 60℃) 配制储备液 | 1 mM | 2.2195 mL | 11.0975 mL | 22.1951 mL | | 5 mM | 0.4439 mL | 2.2195 mL | 4.4390 mL | | 10 mM | 0.2220 mL | 1.1098 mL | 2.2195 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: 2.5 mg/mL (5.55 mM); Suspended solution; Need ultrasonic
此方案可获得 2.5 mg/mL (5.55 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.5 mg/mL (5.55 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (5.55 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 3. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (5.55 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (5.55 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 *以上所有助溶剂都可在本网站选购。
|
m.cnreagent.com