Literature DB >> 28760888

AG-348 enhances pyruvate kinase activity in red blood cells from patients with pyruvate kinase deficiency.

Charles Kung1, Jeff Hixon1, Penelope A Kosinski1, Giovanni Cianchetta1, Gavin Histen1, Yue Chen1, Collin Hill1, Stefan Gross1, Yaguang Si1, Kendall Johnson1, Byron DeLaBarre1, Zhiyong Luo2, Zhiwei Gu2, Gui Yao2, Huachun Tang2, Cheng Fang2, Yingxia Xu2, Xiaobing Lv2, Scott Biller1, Shin-San Michael Su1, Hua Yang1, Janeta Popovici-Muller1, Francesco Salituro1, Lee Silverman1, Lenny Dang1.   

Abstract

Pyruvate kinase (PK) deficiency is a rare genetic disease that causes chronic hemolytic anemia. There are currently no targeted therapies for PK deficiency. Here, we describe the identification and characterization of AG-348, an allosteric activator of PK that is currently in clinical trials for the treatment of PK deficiency. We demonstrate that AG-348 can increase the activity of wild-type and mutant PK enzymes in biochemical assays and in patient red blood cells treated ex vivo. These data illustrate the potential for AG-348 to restore the glycolytic pathway activity in patients with PK deficiency and ultimately lead to clinical benefit.
© 2017 by The American Society of Hematology.

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Year:  2017        PMID： 28760888      PMCID： PMC5609468          DOI： 10.1182/blood-2016-11-753525

Source DB:  PubMed          Journal:  Blood        ISSN： 0006-4971            Impact factor:   22.113


  34 in total

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Journal:  Blood Cells Mol Dis       Date:  2016-01-12       Impact factor: 3.039
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  14 in total

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2.  Diagnosis and clinical management of enzymopathies.

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Journal:  Hematology Am Soc Hematol Educ Program       Date:  2021-12-10

Review 3.  β-Thalassemia: evolving treatment options beyond transfusion and iron chelation.

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Journal:  Hematology Am Soc Hematol Educ Program       Date:  2021-12-10

4.  Mitapivat increases ATP and decreases oxidative stress and erythrocyte mitochondria retention in a SCD mouse model.

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Journal:  Blood Cells Mol Dis       Date:  2022-03-12       Impact factor: 2.372

5.  Decreased activity and stability of pyruvate kinase in sickle cell disease: a novel target for mitapivat therapy.

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Journal:  Blood       Date:  2021-05-27       Impact factor: 22.113

Review 6.  Ineffective Erythropoiesis in β-Thalassaemia: Key Steps and Therapeutic Options by Drugs.

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Review 7.  Metabolomics in cancer research and emerging applications in clinical oncology.

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Authors:  Paola Bianchi; Elisa Fermo
Journal:  Haematologica       Date:  2020-09-01       Impact factor: 9.941

10.  The variable manifestations of disease in pyruvate kinase deficiency and their management.

Authors:  Hanny Al-Samkari; Eduard J Van Beers; Kevin H M Kuo; Wilma Barcellini; Paola Bianchi; Andreas Glenthøj; María Del Mar Mañú Pereira; Richard Van Wijk; Bertil Glader; Rachael F Grace
Journal:  Haematologica       Date:  2020-09-01       Impact factor: 9.941
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