Mitapivat is a small-molecule pharmaceutical active ingredient and an allosteric activator of pyruvate kinase. It is associated with the treatment of anemia in adults with pyruvate kinase deficiency and is also approved for anemia in adults with alpha- or beta-thalassemia in the United States. Mitapivat was initially approved in 2022 for adults with pyruvate kinase deficiency.
The free active moiety of mitapivat has the molecular formula C₂₄H₂₆N₄O₃S, CAS Number 1260075-17-9, and molecular weight 450.56 g/mol.
Mitapivat acts as an allosteric activator of pyruvate kinase, an enzyme involved in glycolysis. Activation of erythrocyte pyruvate kinase can increase ATP production in red blood cells and is relevant to the pharmacological treatment of pyruvate kinase deficiency.
The marketed pharmaceutical form is mitapivat sulfate hydrate. Current U.S. labeling describes the sulfate hydrate as a white to off-white solid that is slightly soluble in water.
Mitapivat is a pyruvate kinase activator used in pharmaceutical applications involving anemia associated with pyruvate kinase deficiency. Current U.S. labeling also includes treatment of anemia in adults with alpha- or beta-thalassemia.
Pyruvate kinase plays an important role in the final stages of glycolysis in red blood cells. Pharmacological activation of pyruvate kinase can improve red-cell energy metabolism and is the basis for mitapivat's therapeutic activity.
Mitapivat is an allosteric activator of pyruvate kinase. In red blood cells, pyruvate kinase catalyzes a key step in glycolysis and contributes to ATP generation.
By activating pyruvate kinase, mitapivat increases pyruvate kinase activity and supports ATP production in erythrocytes. This pharmacological effect is particularly relevant in conditions involving impaired pyruvate kinase function.
Mitapivat API should be evaluated using validated analytical procedures appropriate for its chemical form and intended pharmaceutical application.
Quality characterization may include identity testing, assay, related substances, water content, residual solvents, elemental impurities and other applicable quality attributes.
For commercial pharmaceutical manufacturing, acceptance criteria should follow the applicable approved API specification and validated analytical methods.
Mitapivat exhibits pH-dependent aqueous solubility. Published pharmacokinetic research reports solubilities of approximately 9.72 mg/mL at pH 1.1, 3.20 mg/mL at pH 2.8, 2.23 mg/mL at pH 4.8 and 0.34 mg/mL at pH 5.5. At pH 6.0–8.0, solubility is reported to be below 0.20 mg/mL.
The current U.S. product labeling describes mitapivat sulfate as slightly soluble in water.
Mitapivat API should be stored and handled according to the applicable approved specification, stability data and safety documentation.
Appropriate pharmaceutical handling procedures should be followed to protect the material from contamination and environmental conditions that may affect quality.
Mitapivat API should be packaged in suitable pharmaceutical-grade containers that provide appropriate protection from contamination, moisture and environmental exposure.
Packaging configuration and quantities should be selected according to customer, manufacturing and regulatory requirements.
Mitapivat was initially approved in the United States in 2022 for the treatment of hemolytic anemia in adults with pyruvate kinase deficiency. The FDA subsequently expanded its approved use to include anemia in adults with alpha- or beta-thalassemia.
Regulatory status and approved indications may vary by country and should be evaluated according to the applicable regional requirements.
Mitapivat is a pyruvate kinase activator used in pharmaceutical applications involving anemia associated with pyruvate kinase deficiency and alpha- or beta-thalassemia.
The CAS Number of the mitapivat free active moiety is 1260075-17-9.
The molecular formula of the free mitapivat active moiety is C₂₄H₂₆N₄O₃S.
The molecular weight of the free mitapivat active moiety is approximately 450.56 g/mol.
Mitapivat sulfate hydrate is the pharmaceutical salt form of mitapivat. Current U.S. labeling gives its molecular formula as (C₂₄H₂₆N₄SO₃)₂·H₂SO₄·3H₂O and molecular weight as 1053.23 g/mol.
Mitapivat is used for the treatment of hemolytic anemia in adults with pyruvate kinase deficiency and for anemia in adults with alpha- or beta-thalassemia under current U.S. approvals.
| Parameter | Specification |
|---|---|
| Appearance | White crystalline powder or crystals |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 1.0% |
| Residue on Ignition | NMT 0.5% |
| Heavy Metals | NMT 20 ppm |
| pH (1% Solution) | 5.0 – 7.0 |
| Individual Impurity | NMT 0.5% |
| Total Impurities | NMT 2.0% |
| Water Content | NMT 1.0% |