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> Mitapivat [1260075-17-9]

Mitapivat [1260075-17-9]

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Referencia HY-12689-5mg

embalaje : 5mg

Marca : MedChemExpress

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Descripciòn

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].

IC50 & Target

pyruvate kinase[1][2][3].
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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Mitapivat Related Antibodies

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 AC50 of 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 AC50 of 10.9 nM.
In Vivo

Mitapivat (50 mg/kg; p.o.; twice daily for 21 days) improves anemia in a mouse model for β-thalassemia[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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.
Ensayo clínico
Peso molecular

450.55

Fòrmula

C24H26N4O3S
No. CAS
Appearance

Solid

Color

White to off-white

SMILES

O=S(C1=C2N=CC=CC2=CC=C1)(NC3=CC=C(C(N4CCN(CC5CC5)CC4)=O)C=C3)=O
Envío

Room temperature in continental US; may vary elsewhere.
Almacenamiento
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 2 years
-20°C 1 year
Solvente y solubilidad
In Vitro: 

DMSO : 20.83 mg/mL (46.23 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 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
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: 2.5 mg/mL (5.55 mM); Suspended solution; Need ultrasonic

    This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
  • Protocol 2

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

    Solubility: ≥ 2.5 mg/mL (5.55 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

    Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Pureza y Documentación
Referencias

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