Identification of human lactate dehydrogenase A inhibitors with anti-osteosarcoma activity through cell-based phenotypic screening.,Bioorganic & Medicinal Chemistry Letters

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Identification of human lactate dehydrogenase A inhibitors with anti-osteosarcoma activity through cell-based phenotypic screening.
Bioorganic & Medicinal Chemistry Letters ( IF 2.5 ) Pub Date : 2019-12-18 , DOI: 10.1016/j.bmcl.2019.126909
Fei Wang ₁ , Qiheng Zhao ₁ , Junzhi Liu ₂ , Zhe Wang ₃ , Daliang Kong ₁

Affiliation

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 µM, respectively, and inhibited hLDHA with EC50 values of 3.03, 0.63, and 3.26 µM, respectively.

中文翻译：

通过基于细胞的表型筛选，鉴定具有抗骨肉瘤活性的人乳酸脱氢酶A抑制剂。

人乳酸脱氢酶A在糖酵解过程中起关键作用，因此，在开发抗癌治疗剂中，人们认为对酶的抑制很感兴趣。然而，由于hLDHA结合口袋的高度极性，发现有效的细胞活性hLDHA抑制剂是非常困难的。将基于细胞的表型筛选分析与主要的酶促分析相结合，我们发现了三种细胞活性hLDHA抑制剂，即38、63和374，它们可降低MG-63细胞增殖，IC50值分别为6.47、2.93和6.10 µM。，并抑制hLDHA，EC50值分别为3.03、0.63和3.26 µM。

更新日期：2019-12-18

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