Discovery of potent human lactate dehydrogenase A (LDHA) inhibitors with antiproliferative activity against lung cancer cells: virtual screening and biological evaluation

发现具有抗肺癌细胞增殖活性的强效人乳酸脱氢酶A (LDHA) 抑制剂:虚拟筛选和生物学评价

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Abstract

Human lactate dehydrogenase A (LDHA) plays a crucial role in the promotion of glycolysis in invasive tumor cells, and recently, it has been considered as a vital therapeutic target in the field of oncology. Herein, by combining docking-based virtual screening with in vitro biochemical evaluation, we report the discovery of a potent LDHA inhibitor with antiproliferative activity. The enzymatic assay suggested that the identified compound 7 has a good inhibitory activity (IC(50) = 0.36 μM) against LDHA. The in vitro cytotoxicity assay demonstrated that compound 7 reduces the growth of A549 and NCI-H1975 lung cancer cells, with EC(50) values of 5.5 and 3.0 μM, respectively. These findings indicate that compound 7 could be employed as a useful probe to explore the pharmacology of LDHA.

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