| Size | Price | Stock | Qty |
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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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Purity: ≥98%
Mitapivat (previously PKM2 activator 1020; AG-348; PKR-IN-1; trade name Pyrukynd) is a PKM2 activator (pyruvate kinase activator) that has potential use for the treatment of pyruvate kinase deficiency. As of Feb 2022, Mitapivat has been approved for the treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency. Mitapivat is a potent human R-type pyruvate kinase (PKR) inhibitor that also shows potency for mutant PKR including R510Q PKR, R532W PKR, T384W PKR etc. Pyruvate kinase type M2, which is expressed in multiple tumor cell types and plays a key role in aerobic glycolysis, has nonglycolytic functions and can regulate transcription and cell proliferation. Thus it has been reported that small molecule activators of pyruvate kinase isozyme M2 (PKM2) may suppress tumor formation but have an unknown effect on established tumors.
| ln Vitro |
In healthy donor erythrocytes, mitapivat (0.1 nM-100 μM; 16 h) activates WT PK-R[1]. In red blood cells, mitapivat (0.01 nM-10 μM; 16 h) stimulates ATP generation in a dose-dependent way [1].
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| ln Vivo |
In a mouse model of beta-thalassemia, mitapivat (50 mg/kg; oral; twice daily for 21 days) improves anemia [2].
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: RBC cells Tested Concentrations: 0.1 nM-100 µM Incubation Duration: 16 h (incubate overnight) Experimental Results: 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[1] Cell Types: RBC cells Tested Concentrations: 0.01 nM-10 µM Incubation Duration: 16 h (incubate overnight) Experimental Results: Consistently increased ATP levels in a dose-dependent manner by an average of 60% over DMSO control with an AC50 of 10.9 nM. |
| Animal Protocol |
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. |
| References |
[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. |
| Molecular Formula |
C24H26N4O3S
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| Molecular Weight |
450.56
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| CAS # |
1260075-17-9
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| Related CAS # |
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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| Chemical Name |
N-{4-[4-(cyclopropylmethyl)piperazine-1-carbonyl]phenyl}quinoline-8-sulfonamide
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| Synonyms |
PKM2 activator 1020; AG348; PKM2 activator; PKR-IN-1; AG-348; PKR-IN-1; trade name Pyrukynd
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
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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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
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. |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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