| 规格 | 价格 | 库存 | 数量 |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| Other Sizes |
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| 体外研究 (In Vitro) |
在健康供体红细胞中，mitapivat（0.1 nM-100 μM；16 小时）可激活 WT PK-R[1]。在红细胞中，mitapivat（0.01 nM-10 μM；16 小时）以剂量依赖性方式刺激 ATP 生成 [1]。
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| 体内研究 (In Vivo) |
在β-地中海贫血小鼠模型中，mitapivat（50 mg/kg；口服；每天两次，持续 21 天）可改善贫血[2]。
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| 细胞实验 |
细胞活力测定[1]
细胞类型： RBC 细胞 测试浓度： 0.1 nM-100 µM 孵育时间： 16 小时（孵育过夜） 实验结果： PK-R 活性以剂量依赖性方式增加至 DMSO 对照的约 2.5 倍，AC50 为 62 nM。 细胞活力测定[1] 细胞类型： RBC 细胞 测试浓度： 0.01 nM-10 µM 孵育时间：16 小时（孵育过夜） 实验结果：以剂量依赖性方式持续增加 ATP 水平，比 DMSO 对照平均增加 60%，AC50 为10.9纳米。 |
| 动物实验 |
Animal/Disease Models: WT C57B6 and Hbbth3/+ mice (both are 2-month-old female mice; β-thalassemia model)[2].
Doses: 50 mg/kg Route of Administration: In animal feedings; single daily for 3 weeks. Experimental Results: 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/Disease Models: WT C57B6 and Hbbth3/+ mice (both are 2-month-old female mice; β-thalassemia model)[2]. Doses: 50 mg/kg Route of Administration: po (oral gavage), twice (two times) daily for 21 days. Experimental Results: Ameliorated ineffective erythropoiesis and anemia in Hbbth3/+ mice and increased ATP, decreased ROS production, as well as decreased 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. |
| 分子式 |
C24H26N4O3S
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|---|---|
| 分子量 |
450.56
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| CAS号 |
1260075-17-9
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| 相关CAS号 |
2151847-10-6 (sulfate hydrate);1260075-17-9 (free);2329710-91-8 (sulfate);
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| SMILES |
O=S(C1=C2N=CC=CC2=CC=C1)(NC3=CC=C(C(N4CCN(CC5CC5)CC4)=O)C=C3)=O
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| 化学名 |
N-{4-[4-(cyclopropylmethyl)piperazine-1-carbonyl]phenyl}quinoline-8-sulfonamide
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| 别名 |
PKM2 activator 1020; AG348; PKM2 activator; PKR-IN-1; AG-348; PKR-IN-1; trade name Pyrukynd
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| 存储方式 |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| 运输条件 |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| 溶解度 (体外) |
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| 溶解度 (体内) |
Solubility in Formulation 1: 2.5 mg/mL (5.55 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.55 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.55 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. 1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液)); 2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方): 10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline); 假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL； 3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例; 4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶; 5、为保证最佳实验结果，工作液请现配现用！ 6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们; 7、 以上所有助溶剂都可在 Invivochem.cn网站购买。 |
| 制备储备液 | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2195 mL | 11.0973 mL | 22.1946 mL | |
| 5 mM | 0.4439 mL | 2.2195 mL | 4.4389 mL | |
| 10 mM | 0.2219 mL | 1.1097 mL | 2.2195 mL |
1、根据实验需要选择合适的溶剂配制储备液 (母液)：对于大多数产品，InvivoChem推荐用DMSO配置母液 (比如：5、10、20mM或者10、20、50 mg/mL浓度），个别水溶性高的产品可直接溶于水。产品在DMSO 、水或其他溶剂中的具体溶解度详见上”溶解度 (体外)”部分;
2、如果您找不到您想要的溶解度信息，或者很难将产品溶解在溶液中，请联系我们;
3、建议使用下列计算器进行相关计算（摩尔浓度计算器、稀释计算器、分子量计算器、重组计算器等）;
4、母液配好之后，将其分装到常规用量，并储存在-20°C或-80°C，尽量减少反复冻融循环。
计算结果:
工作液浓度： mg/mL；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL)。如该浓度超过该批次药物DMSO溶解度，请首先与我们联系。
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL ddH2O，混匀澄清。
(1) 请确保溶液澄清之后，再加入下一种溶剂 (助溶剂) 。可利用涡旋、超声或水浴加热等方法助溶；
(2) 一定要按顺序加入溶剂 (助溶剂) 。
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