Identification of human lactate dehydrogenase A inhibitors with anti-osteosarcoma activity through cell-based phenotypic screening

被引：4

作者：

Wang, Fei ^{[1
]}

Zhao, Qiheng ^{[1
]}

Liu, Junzhi ^{[2
]}

Wang, Zhe ^{[3
]}

Kong, Daliang ^{[1
]}

机构：

[1] Jilin Univ, Dept Orthopaed, China Japan Union Hosp, Jilin 130030, Jilin, Peoples R China

[2] Jilin Univ, Dept Qual Control, China Japan Union Hosp, Jilin 130030, Jilin, Peoples R China

[3] Jilin Univ, Sch Basic Med, Dept Pathol, Jilin 130000, Jilin, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2020年 / 30卷 / 04期

关键词：

Lactate dehydrogenase A; Glycolysis; Anticancer; Cancer metabolism; CANCER; DISCOVERY; POTENT;

D O I：

10.1016/j.bmcl.2019.126909

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Human lactate dehydrogenase A plays a key role in the glycolytic process, the inhibition of the enzyme is therefore considered of interest in developing anticancer therapeutics. However, due to the highly polar nature of hLDHA binding pocket, it is very challenge to discover potent cellular active hLDHA inhibitor. Combined a cell-based phenotypic screening assay with a primary enzymatic assay, we discovered three cellular active hLDHA inhibitors, namely 38, 63, and 374, which reduced MG-63 cell proliferation with IC50 values of 6.47, 2.93, and 6.10 mu M, respectively, and inhibited hLDHA with EC50 values of 3.03, 0.63, and 3.26 mu M, respectively.

引用

页数：5

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