化学
癌细胞
丙酮酸激酶
丙酮酸脱氢酶复合物
生物化学
癌症
氧化磷酸化
丙酮酸脱氢酶激酶
激酶
酶
癌症研究
细胞生物学
糖酵解
生物
遗传学
作者
Yiyang Li,Zhipeng Xie,Xiaoyong Lei,Xiaoyan Yang,Sheng Huang,Wenjie Yuan,Xin Deng,Zhe Wang,Guotao Tang
标识
DOI:10.1016/j.bioorg.2024.107160
摘要
Metabolism is reprogrammed in a variety of cancer cells to ensure their rapid proliferation. Cancer cells prefer to utilize glycolysis to produce energy as well as to provide large amounts of precursors for their division. In this process, cancer cells inhibit the activity of pyruvate dehydrogenase complex (PDC) by upregulating the expression of pyruvate dehydrogenase kinases (PDKs). Inhibiting the activity of PDKs in cancer cells can effectively block this metabolic transition in cancer cells, while also activating mitochondrial oxidative metabolism and promoting apoptosis of cancer cells. To this day, the study of PDKs inhibitors has become one of the research hotspots in the field of medicinal chemistry. Novel structures targeting PDKs are constantly being discovered, and some inhibitors have entered the clinical research stage. Here, we reviewed the research progress of PDKs inhibitors in recent years and classified them according to the PDKs binding sites they acted on, aiming to summarize the structural characteristics of inhibitors acting on different binding sites and explore their clinical application value. Finally, the shortcomings of some PDKs inhibitors and the further development direction of PDKs inhibitors are discussed.
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