Identification of a potent inhibitor targeting human lactate dehydrogenase A and its metabolic modulation for cancer cell line

被引：19
|
作者：
Chen, Chun-Ye [1 ]
Feng, Yan [2 ,3 ]
Chen, Jing-Yu [4 ]
Deng, Hao [5 ]
机构：
[1] Chongqing Univ, Key Lab Biorheol Sci & Technol, Minist Educ, Bioengn Coll, Chongqing 400030, Peoples R China
[2] Third Mil Med Univ, Ctr Canc, Daping Hosp, Chongqing 400042, Peoples R China
[3] Third Mil Med Univ, Inst Surg Res, Chongqing 400042, Peoples R China
[4] Third Mil Med Univ, Southwest Hosp, Dept Neurosurg, Chongqing 400038, Peoples R China
[5] Third Mil Med Univ, Inst Hepatobiliary Surg, Southwest Hosp, Chongqing 400038, Peoples R China
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2016年 / 26卷 / 01期
关键词：
Lactate dehydrogenase A; Virtual screening; Enzymatic assay; Cytotoxic assay; ISOFORM; NADH; LEAD;
D O I：
10.1016/j.bmcl.2015.11.025
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Targeting LDHA represents a promising strategy for the development of new anti-cancer agents. We report herein the identification of a potent compound as a direct LDHA inhibitor. The in vitro enzymatic assay revealed that the VS-2 had good inhibitory potency (IC50 = 0.25 mu M) to LDHA. Cytotoxic assay suggested that the VS-2 could inhibit MCF-7 cancer cell growth, with the IC50 value low to 1.54 mu M. The sea-horse XF24 experiment validated that the VS-2 served as a modulator to reprogram MCF-7 cancer cell metabolism from glycolysis to mitochondrial respiration. (C) 2015 Elsevier Ltd. All rights reserved.
引用
收藏
页码：72 / 75
页数：4
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