Mitapivat AG-348|cas:1260075-17-9|西域试剂

Mitapivat AG-348,99.85%

产品编号：Bellancom-12689| CAS NO：1260075-17-9| 分子式：C₂₄H₂₆N₄O₃S| 分子量：450.55

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货号	价格	库存与货期
Bellancom-12689	￥950.00	杭州北京（现货）
Bellancom-12689	￥1520.00	杭州北京（现货）
Bellancom-12689	￥5350.00	杭州北京（现货）
Bellancom-12689	￥8560.00	杭州北京（现货）

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Mitapivat AG-348

产品介绍

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 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.

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.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

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
(In Vivo)

Mitapivat (50 mg/kg; p.o.; twice daily for 21 days) improves anemia in a mouse model for β-thalassemia.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	WT C57B6 and Hbb^th3/+ 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 Hbbth^3/+ mice. Elevated pyruvate kinase activity in cells from Hbbth^3/+ mice, and markedly increased ROS level in erythrocytes. Increased the expression of PKM2 in polychromatic and orthochromatic erythroblasts of Hbbth^3/+ mice.

Animal Model:	WT C57B6 and Hbb^th3/+ 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 Hbb^th3/+ mice and increased ATP, reduced ROS production, as well as reduced markers of mitochondrial dysfunction associated with improved mitochondrial clearance.

体内研究

Mitapivat (50 mg/kg; p.o.; twice daily for 21 days) improves anemia in a mouse model for β-thalassemia.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	WT C57B6 and Hbb^th3/+ 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 Hbbth^3/+ mice. Elevated pyruvate kinase activity in cells from Hbbth^3/+ mice, and markedly increased ROS level in erythrocytes. Increased the expression of PKM2 in polychromatic and orthochromatic erythroblasts of Hbbth^3/+ mice.

Animal Model:	WT C57B6 and Hbb^th3/+ 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 Hbb^th3/+ mice and increased ATP, reduced ROS production, as well as reduced markers of mitochondrial dysfunction associated with improved mitochondrial clearance.

体内研究

Mitapivat (50 mg/kg; p.o.; twice daily for 21 days) improves anemia in a mouse model for β-thalassemia.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	WT C57B6 and Hbb^th3/+ 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 Hbbth^3/+ mice. Elevated pyruvate kinase activity in cells from Hbbth^3/+ mice, and markedly increased ROS level in erythrocytes. Increased the expression of PKM2 in polychromatic and orthochromatic erythroblasts of Hbbth^3/+ mice.

Animal Model:	WT C57B6 and Hbb^th3/+ 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 Hbb^th3/+ mice and increased ATP, reduced ROS production, as well as reduced markers of mitochondrial dysfunction associated with improved mitochondrial clearance.

性状

Solid

溶解性数据

In Vitro:

DMSO : 20.83 mg/mL (46.23 mM; ultrasonic and warming and heat to 60°C)

配制储备液

浓度溶剂体积质量	1 mg	5 mg	10 mg

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°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 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。
将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液
2.

请依序添加每种溶剂： 10% DMSO 90% (20% SBE-β-CD in 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 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。
将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
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。