ReviewTherapeutic advances in hematology2021
Mitapivat, a novel pyruvate kinase activator, for the treatment of hereditary hemolytic anemias.
Review in Therapeutic advances in hematology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 70 citations in OpenAlex.
- Relative Bioavailability Studies With Mitapivat: Formulation and Food Effect Assessments in Healthy Subjects.Clinical pharmacology in drug development · 2024Trial
- Two Novel PKLR Variants in Pyruvate Kinase Deficiency: Insights From Clinical, Molecular and Functional Analysis.International journal of laboratory hematology · 2026Article
- Recent Advances in Thalassemia Research: A Comprehensive Assessment From Diagnostic Technologies to Clinical Treatment.Journal of clinical laboratory analysis · 2026Review
- Mitapivat for sickle cell disease: the time is ripe for a new therapy.Annals of translational medicine · 2026Article
- The return of metabolism: biochemistry and physiology of glycolysis.Biological reviews of the Cambridge Philosophical Society · 2026Review
- CCND3 Suppression Ameliorates β-Thalassaemia in a Murine Disease Model: A Potential Therapeutic Strategy.Cells · 2026Article
- From structural insight to molecule: Integrative molecular simulations identify candidate pyruvate kinase activators.PloS one · 2026Article
- SNH-119014, a novel pyruvate kinase activator, enhances ATP production and reduces oxidative stress in erythroid cells from patients with β-thalassemia major.Frontiers in pharmacology · 2026Article
- Not-So-Rare Defects of RBC Lipidic Composition: Four New Cases of Flippase Deficiency Due toInternational journal of molecular sciences · 2025Article
- Mitapivat for Acquired Pyruvate Kinase Deficiency.Pediatric blood & cancer · 2025Article
- Mitapivat for phosphofructokinase deficiency.American journal of hematology · 2024Article
- Novel sulfonamides unveiled as potent anti-lung cancer agentsRSC medicinal chemistry · 2024Article
- Ualign: pushing the limit of template-free retrosynthesis prediction with unsupervised SMILES alignment.Journal of cheminformatics · 2024Article
- Understanding Rare Anemias: Emerging Frontiers for Diagnosis and Treatment.Journal of clinical medicine · 2024Review
- Bone mineral density in adult patients with pyruvate kinase deficiency on long-term mitapivat treatment.Haematologica · 2024Article
- Article
- Modulation of the allosteric and vasoregulatory arms of erythrocytic oxygen transport.Frontiers in physiology · 2024Review
- An innovative phase I study in healthy subjects to determine the mass balance, elimination, metabolism, and absolute bioavailability of mitapivat.Clinical and translational science · 2023Article
- Synthesis and clinical application of new drugs approved by FDA in 2022.Molecular biomedicine · 2023Review
- Therapeutic perspective for children and young adults living with thalassemia and sickle cell disease.European journal of pediatrics · 2023Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitapivat (AG-348) is a novel, first-in-class oral small molecule allosteric activator of the pyruvate kinase enzyme. Mitapivat has been shown to significantly upregulate both wild-type and numerous mutant forms of erythrocyte pyruvate kinase (PKR), increasing adenosine triphosphate (ATP) production and reducing levels of 2,3-diphosphoglycerate. Given this mechanism, mitapivat has been evaluated in clinical trials in a wide range of hereditary hemolytic anemias, including pyruvate kinase deficiency (PKD), sickle cell disease, and the thalassemias. The clinical development of mitapivat in adults with PKD is nearly complete, with the completion of two successful phase III clinical trials demonstrating its safety and efficacy. Given these findings, mitapivat has the potential to be the first approved therapeutic for PKD. Mitapivat has additionally been evaluated in a phase II trial of patients with alpha- and beta-thalassemia and a phase I trial of patients with sickle cell disease, with findings suggesting safety and efficacy in these more common hereditary anemias. Following these successful early-phase trials, two phase III trials of mitapivat in thalassemia and a phase II/III trial of mitapivat in sickle cell disease are beginning worldwide. Promising preclinical studies have additionally been done evaluating mitapivat in hereditary spherocytosis, suggesting potential efficacy in erythrocyte membranopathies as well. With convenient oral dosing and a safety profile comparable with placebo in adults with PKD, mitapivat is a promising new therapeutic for several hereditary hemolytic anemias, including those without any currently US Food and Drug Administration (FDA) or European Medicines Agency (EMA)-approved drug therapies. This review discusses the preclinical studies, pharmacology, and clinical trials of mitapivat.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.