Recent advances in pyruvate dehydrogenase kinase inhibitors: Structures, inhibitory mechanisms and biological activities

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成果类型：

期刊论文

作者：

Li, Yiyang;Xie, Zhizhong;Lei, Xiaoyong;Yang, Xiaoyan;Huang, Sheng;...

通讯作者：

Tang, GT;Wang, Z;Deng, XP

作者机构：

[Yang, Xiaoyan; Xie, Zhizhong; Lei, Xiaoyong; Yuan, Weixi; Tang, Guotao; Li, Yiyang] Univ South China, Inst Pharm & Pharmacol, Hengyang Med Sch, Hunan Prov Key Lab Tumor Microenvironm Respons Dru, Hengyang 421001, Hunan, Peoples R China.

[Wang, Zhe; Wang, Z] Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Pharm, Hengyang 421001, Hunan, Peoples R China.

[Deng, Xiangping; Deng, XP] Univ South China, Hengyang Med Sch, Pharm Dept, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China.

[Huang, Sheng] Hunan Jiuzhitang Co Ltd, Changsha 410007, Hunan, Peoples R China.

通讯机构：

[Wang, Z ; Deng, XP ; Tang, GT ] U

Univ South China, Inst Pharm & Pharmacol, Hengyang Med Sch, Hunan Prov Key Lab Tumor Microenvironm Respons Dru, Hengyang 421001, Hunan, Peoples R China.

Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Pharm, Hengyang 421001, Hunan, Peoples R China.

Univ South China, Hengyang Med Sch, Pharm Dept, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China.

语种：

英文

关键词：

Glycolysis;Inhibitor;Metabolic reprogramming;Pyruvate dehydrogenase kinase;Structure-activity relationship

期刊：

Bioorganic Chemistry

ISSN：

0045-2068

年：

2024

卷：

144

页码：

107160

DOI：

10.1016/j.bioorg.2024.107160

基金类别：

National Natural Science Foundation of China [82304420]; Natural Science Foundation of Hunan Province [2023JJ40576]; Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research [2019TP1041]; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study

机构署名：

本校为第一且通讯机构

院系归属：

药学与生物科学学院

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...

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Recent advances in pyruvate dehydrogenase kinase inhibitors: Structures, inhibitory mechanisms and biological activities

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