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

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

  • Blood. 2017 Sep 14;130(11):1347-1356. doi: 10.1182/blood-2016-11-753525.
Charles Kung 1 Jeff Hixon 1 Penelope A Kosinski 1 Giovanni Cianchetta 1 Gavin Histen 1 Yue Chen 1 Collin Hill 1 Stefan Gross 1 Yaguang Si 1 Kendall Johnson 1 Byron DeLaBarre 1 Zhiyong Luo 2 Zhiwei Gu 2 Gui Yao 2 Huachun Tang 2 Cheng Fang 2 Yingxia Xu 2 Xiaobing Lv 2 Scott Biller 1 Shin-San Michael Su 1 Hua Yang 1 Janeta Popovici-Muller 1 Francesco Salituro 1 Lee Silverman 1 Lenny Dang 1
Affiliations

Affiliations

  • 1 Agios Pharmaceuticals, Inc., Cambridge, MA; and.
  • 2 Shanghai ChemPartner Co., Ltd., Shanghai, China.
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.

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