ArticleBlood advances2021
FT-4202, an oral PKR activator, has potent antisickling effects and improves RBC survival and Hb levels in SCA mice.
Article in Blood advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- One-year safety and efficacy of mitapivat in sickle cell disease: follow-up results of a phase 2, open-label study.Blood advances · 2023Trial
- Safety, Pharmacokinetics, and Pharmacodynamics of Etavopivat (FT-4202), an Allosteric Activator of Pyruvate Kinase-R, in Healthy Adults: A Randomized, Placebo-Controlled, Double-Blind, First-in-Human Phase 1 Trial.Clinical pharmacology in drug development · 2022Trial
- The pyruvate kinase activator etavopivat (FT-4202) limits pulmonary and systemic sequelae of sepsis in a mouse LPS model.American journal of physiology. Lung cellular and molecular physiology · 2026Article
- Evaluating anti-sickling therapies for sickle cell disease: a microfluidic assay for red blood cell-mediated microvascular occlusion under hypoxia.Lab on a chip · 2025Article
- Article
- A review on disease modifying pharmacologic therapies for sickle cell disease.Annals of hematology · 2025Review
- Endogenous small molecule effectors in GATA transcription factor mechanisms governing biological and pathological processes.Experimental hematology · 2024Review
- Article
- Modulation of the allosteric and vasoregulatory arms of erythrocytic oxygen transport.Frontiers in physiology · 2024Review
- Pyruvate kinase activators: targeting red cell metabolism in sickle cell disease.Hematology. American Society of Hematology. Education Program · 2023Article
- Defining global strategies to improve outcomes in sickle cell disease: a Lancet Haematology Commission.The Lancet. Haematology · 2023Review
- In vivo evaluation of the effect of sickle cell hemoglobin S, C and therapeutic transfusion on erythrocyte metabolism and cardiorenal dysfunction.American journal of hematology · 2023Article
- Mitapivat increases ATP and decreases oxidative stress and erythrocyte mitochondria retention in a SCD mouse model.Blood cells, molecules & diseases · 2022Article
- Limitations of mouse models for sickle cell disease conferred by their human globin transgene configurations.Disease models & mechanisms · 2022Article
- Revisiting anemia in sickle cell disease and finding the balance with therapeutic approaches.Blood · 2022Article
- Generation and Export of Red Blood Cell ATP in Health and Disease.Frontiers in physiology · 2021Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sickle cell anemia (SCA) results from an abnormal sickle hemoglobin (HbS). HbS polymerizes upon deoxygenation, resulting in red blood cell (RBC) sickling and membrane damage that cause vaso-occlusions and hemolysis. Sickle RBCs contain less adenosine triphosphate and more 2,3-diphosphoglycerate than normal RBCs, which allosterically reduces hemoglobin (Hb) oxygen (O2) affinity (ie, increases the partial pressure of oxygen at which hemoglobin is 50% saturated with oxygen [P50]), potentiating HbS polymerization. Herein, we tested the effect of investigational agent FT-4202, an RBC pyruvate kinase (PKR) activator, on RBC sickling and membrane damage by administering it to Berkeley SCA mice. Two-week oral FT-4202 administration was well tolerated, decreasing HbS P50 to levels similar to HbA and demonstrating beneficial biological effects. In FT-4202-treated animals, there was reduced sickling in vivo, demonstrated by fewer irreversibly sickled cells, and improved RBC deformability, assessed at varying shear stress. Controlled deoxygenation followed by reoxygenation of RBCs obtained from the blood of FT-4202-treated mice showed a shift in the point of sickling to a lower partial pressure of oxygen (pO2). This led to a nearly 30% increase in RBC survival and a 1.7g/dL increase in Hb level in the FT-4202-treated SCA mice. Overall, our results in SCA mice suggest that FT-4202 might be a potentially useful oral antisickling agent that warrants investigation in patients with SCA.
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