Glycolysis is enhanced in cancer cells. Cancer cells utilize glycolysis as their primary energy source, even under aerobic conditions. This is known as the Warburg effect. Thus, effective inhibition of the glycolytic pathway is a crucial component of cancer therapy. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an important enzyme in glycolysis and overexpresses in cancers. Therefore, targeting GAPDH to inhibit its role in glycolysis is important for GAPDH functional studies and the treatment of cancers. However, only a few GAPDH inhibitors have been reported. In our current study, we identified a GAPDH inhibitor, DC-5163, using docking-based virtual screening and biochemical and biophysical analysis. DC-5163 is a small molecule compound that inhibits GAPDH enzyme activity and cancer cell proliferation (normal cells were tolerant to it). It can inhibit glycolysis pathway partially, which was manifested by decreased glucose uptake and lactic acid production. And it also leaded to cell death through apoptotic pathways. This study reflects the pivotal role of GAPDH in cancer cells and demonstrates that DC-5163 is a useful inhibitor and can be of value in studying the role of GAPDH and the development of new clinical cancer treatments.

中文翻译：

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通过基于对接的虚拟筛选发现新型3-磷酸甘油醛脱氢酶抑制剂。

糖酵解在癌细胞中得到增强。即使在有氧条件下，癌细胞也利用糖酵解作为主要能源。这被称为沃堡效应。因此，有效抑制糖酵解途径是癌症治疗的关键组成部分。3-磷酸​​甘油醛脱氢酶（GAPDH）是糖酵解中的重要酶，在癌症中过表达。因此，靶向GAPDH以抑制其在糖酵解中的作用对于GAPDH功能研究和癌症治疗非常重要。但是，仅报道了几种GAPDH抑制剂。在我们当前的研究中，我们使用基于对接的虚拟筛选以及生化和生物物理分析鉴定了GAPDH抑制剂DC-5163。DC-5163是抑制GAPDH酶活性和癌细胞增殖的小分子化合物（正常细胞对此具有耐受性）。它可以部分抑制糖酵解途径，这表现为葡萄糖摄取减少和乳酸产生。而且它还通过凋亡途径导致细胞死亡。这项研究反映了GAPDH在癌细胞中的关键作用，并证明DC-5163是一种有用的抑制剂，在研究GAPDH的作用和新的临床癌症治疗方法的开发中可能具有价值。