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

被引：87

作者：

Kung, Charles ^{[1
]}

Hixon, Jeff ^{[1
]}

Kosinski, Penelope A. ^{[1
]}

Cianchetta, Giovanni ^{[1
]}

Histen, Gavin ^{[1
]}

Chen, Yue ^{[1
]}

Hill, Collin ^{[1
]}

Gross, Stefan ^{[1
]}

Si, Yaguang ^{[1
]}

Johnson, Kendall ^{[1
]}

DeLaBarre, Byron ^{[1
]}

Luo, Zhiyong ^{[2
]}

Gu, Zhiwei ^{[2
]}

Yao, Gui ^{[2
]}

Tang, Huachun ^{[2
]}

Fang, Cheng ^{[2
]}

Xu, Yingxia ^{[2
]}

Lv, Xiaobing ^{[2
]}

Biller, Scott ^{[1
]}

Su, Shin-San Michael ^{[1
]}

Yang, Hua ^{[1
]}

Popovici-Muller, Janeta ^{[1
]}

Salituro, Francesco ^{[1
]}

Silverman, Lee ^{[1
]}

Dang, Lenny ^{[1
]}

机构：

[1] Agios Pharmaceut Inc, Cambridge, MA USA

[2] Shanghai ChemPartner Co Ltd, Shanghai, Peoples R China

来源：

BLOOD | 2017年 / 130卷 / 11期

关键词：

NONSPHEROCYTIC HEMOLYTIC-ANEMIA; PK-LR GENE; RIBOFLAVIN TREATMENT; STEM-CELLS; ERYTHROCYTE; GENERATION; CANCER; ENZYME; MUTANT;

D O I：

10.1182/blood-2016-11-753525

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：1347 / 1356

页数：10

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