Results 1 to 10 of about 336 (99)

Mitapivat, a novel pyruvate kinase activator, for the treatment of hereditary hemolytic anemias

Therapeutic Advances in Hematology, 2021
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 ...
Hanny Al-Samkari, Eduard Van Beers
exaly   +2 more sources

An innovative phase I study in healthy subjects to determine the mass balance, elimination, metabolism, and absolute bioavailability of mitapivat [PDF]

Clinical and Translational Science, 2023
Mitapivat, a first‐in‐class, oral, small‐molecule, allosteric activator of the red blood cell‐specific form of pyruvate kinase (PKR), was approved for the treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency.
Chandra Prakash, Heidi Mangus, Yan Yan, Hua Yang, Varsha Iyer   +4 more
doaj   +2 more sources

Mitapivat metabolically reprograms human β-thalassemic erythroblasts, increasing their responsiveness to oxidation [PDF]

Blood Advances
: β-thalassemia (β-thal) is a worldwide hereditary red cell disorder characterized by severe chronic anemia. Recently, the pyruvate kinase (PK) activator mitapivat has been shown to improve anemia and ineffective erythropoiesis in a mouse model of β-thal
Angela Siciliano, Angelo D’Alessandro, Alessandro Matte, Giovanni Bisello, Mariarita Bertoldi, Monika Dzieciatkowska, Amy Argabright, Richard Huot Pozzetto, Veronica Riccardi, Andrea Mattarei, Alberto Ongaro, Jacopo Ceolan, Roberta Russo, Leonardo Rivadeneyra, Megan Wind-Rotolo, Achille Iolascon, Carlo Brugnara, Lucia De Franceschi   +17 more
doaj   +2 more sources

How We Treat Hemolytic Anemia Due to Pyruvate Kinase Deficiency [PDF]

Hematology Reports
Background: Pyruvate kinase (PK) deficiency is an inherited red blood cell (RBC) enzyme disorder that results in non-immune chronic hemolytic anemia. Characteristic symptoms of PK deficiency include anemia, fatigue, splenomegaly, jaundice, gallstones ...
Sara Tama-Shekan, Valeria Moreno, Ludovic Saba, Chakra P. Chaulagain   +3 more
doaj   +2 more sources

Mitapivat reprograms the RBC metabolome and improves anemia in a mouse model of hereditary spherocytosis [PDF]

JCI Insight, 2023
Hereditary spherocytosis (HS) is the most common, nonimmune, hereditary, chronic hemolytic anemia after hemoglobinopathies. The genetic defects in membrane function causing HS lead to perturbation of the RBC metabolome, with altered glycolysis.
Alessandro Matte, Anand B. Wilson, Federica Gevi, Enrica Federti, Antonio Recchiuti, Giulia Ferri, Anna Maria Brunati, Mario Angelo Pagano, Roberta Russo, Christophe Leboeuf, Anne Janin, Anna Maria Timperio, Achille Iolascon, Elisa Gremese, Lenny Dang, Narla Mohandas, Carlo Brugnara, Lucia De Franceschi   +17 more
doaj   +2 more sources

Functional and multi-omics signatures of mitapivat efficacy upon activation of pyruvate kinase in red blood cells from patients with sickle cell disease [PDF]

Haematologica
Mitapivat, a pyruvate kinase (PK) activator, shows great potential as a sickle cell disease (SCD)- modifying therapy. Safety and efficacy of mitapivat as a long-term maintenance therapy is currently being evaluated in two open-label studies.
Angelo D’Alessandro, Kang Le, Maureen Lundt, Quan Li, Emily B. Dunkelberger, Troy Cellmer, Andrew J. Worth, Spurthi Patil, Chris Huston, Abby Grier, Monika Dzieciatkowska, Daniel Stephenson, William A. Eaton, Swee Lay Thein   +13 more
doaj   +2 more sources

Designing a single-arm phase 2 clinical trial of mitapivat for adult patients with erythrocyte membranopathies (SATISFY): a framework for interventional trials in rare anaemias – pilot study protocol [PDF]

BMJ Open
Introduction Membranopathies encompass haemolytic disorders arising from genetic variants in erythrocyte membrane proteins, including hereditary spherocytosis and stomatocytosis.
Niels Vejlstrup, Pierre Fenaux, Jesper Petersen, Eduard J van Beers, Andreas Glenthøj, Kevin H M Kuo, Richard van Wijk, Minke A E Rab, Evelyn Groot, Nina Toft, Selma Kofoed Bendtsen, Jens Helby, Fatiha Chermat   +12 more
doaj   +2 more sources

Metabolic blood profile and response to treatment with the pyruvate kinase activator mitapivat in patients with sickle cell disease [PDF]

HemaSphere
Mitapivat is an investigational, oral, small‐molecule allosteric activator of pyruvate kinase (PK). PK is a regulatory glycolytic enzyme that is key in providing the red blood cell (RBC) with sufficient amounts of adenosine triphosphate (ATP).
Myrthe J. vanDijk, Titine J. J. Ruiter, Sigrid van derVeen, Minke A. E. Rab, Brigitte A. vanOirschot, Jennifer Bos, Cleo Derichs, Anita W. Rijneveld, Marjon H. Cnossen, Erfan Nur, Bart J. Biemond, Marije Bartels, Roger E. G. Schutgens, Wouter W. vanSolinge, Judith J. M. Jans, Eduard J. vanBeers, Richard vanWijk   +16 more
doaj   +2 more sources

High Resolution Crystal Structure of the Pyruvate Kinase Tetramer in Complex with the Allosteric Activator Mitapivat/AG-348

Crystals
Pyruvate kinase (PK) deficiency is a rare genetic disorder that affects this critical enzyme within the glycolysis pathway. In recent years, Mitapivat (MTPV, AG-348) has emerged as a notable allosteric activator for treating PK deficiency.
Cheng Zhang, Adil Mardinoğlu, Renhua Sun   +2 more
exaly   +3 more sources

SNH-119014, a novel pyruvate kinase activator, enhances ATP production and reduces oxidative stress in erythroid cells from patients with β-thalassemia major [PDF]

Frontiers in Pharmacology
BackgroundThalassemia is a common disease worldwide. Oxidative stress contributes to ineffective erythropoiesis and hemolysis in β-thalassemia major (β-TM).
Qiulin Huang, Yumei Huang, Lingyuan Pan, Rongrong Liu, Rongrong Liu, Rongrong Liu, Rongrong Liu, Yongrong Lai, Yongrong Lai, Yongrong Lai, Yongrong Lai   +10 more
doaj   +2 more sources