Identification of 2-amino-5-aryl-pyrazines as inhibitors of human lactate dehydrogenase
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- 作者：Benjamin P. Fauber ; Peter S. Dragovich ; Jinhua Chen ; Laura B. Corson ; Charles Z. Ding ; Charles Eigenbrot ; Anthony M. Giannetti ; Thomas Hunsaker ; Sharada Labadie ; Yichin Liu ; Yingchun Liu ; Shiva Malek ; David Peterson ; Keith Pitts ; Steve Sideris ; Mark Ultsch ; Erica V ; erPorten ; Jing Wang ; BinQing Wei ; Ivana Yen ; et al.
- 关键词：Lactate dehydrogenase ; X-ray crystal structure ; Pyrazine ; Tumor metabolism
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2013
- 出版时间：15 October, 2013
- 年：2013
- 卷：23
- 期：20
- 页码：5533-5539
- 全文大小：2905 K
文摘
A 2-amino-5-aryl-pyrazine was identified as an inhibitor of human lactate dehydrogenase A (LDHA) via a biochemical screening campaign. Biochemical and biophysical experiments demonstrated that the compound specifically interacted with human LDHA. Structural variation of the screening hit resulted in improvements in LDHA biochemical inhibition and pharmacokinetic properties. A crystal structure of an improved compound bound to human LDHA was also obtained and it explained many of the observed structure-activity relationships.