| Identification | Back Directory | [Name]
PKR-IN-1 | [CAS]
1260075-17-9 | [Synonyms]
ag348
AG-348
CS-2722
PKR-IN-1
Mitapivat
PKM2 activator
cas 1260075-17-9
AG348;AG348;AG-348
PKM2 activator 1020
MITAPIVAT;PKM2 ACTIVATOR;CAS 1260075-17-9
N-(4-(4-(cyclopropylmethyl)piperazine-1-carbonyl)phenyl)quinoline-8-sulfonamide
N-(4-{[4-(Cyclopropylmethyl)-1-piperazinyl]carbonyl}phenyl)-8-quinolinesulfonamide
8-Quinolinesulfonamide, N-[4-[[4-(cyclopropylmethyl)-1-piperazinyl]carbonyl]phenyl]- | [EINECS(EC#)]
604-604-1 | [Molecular Formula]
C24H26N4O3S | [MDL Number]
MFCD26936342 | [MOL File]
1260075-17-9.mol | [Molecular Weight]
450.55 |
| Chemical Properties | Back Directory | [Boiling point ]
667.3±65.0 °C(Predicted) | [density ]
1.369±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO : 50 mg/mL (110.98 mM) | [form ]
Solid | [pka]
6.69±0.50(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
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[1][2][3]. | [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.
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| 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. |
| [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. DOI:10.1182/blood-2016-11-753525
[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. DOI:10.1172/JCI144206
[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. DOI:10.3324/haematol.2019.238865 |
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