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Discovery of novel glyceraldehyde-3-phosphate dehydrogenase inhibitor via docking-based virtual screening

文献类型：期刊论文

作者Li, Ting2; Tan, Xiaoqin3,4; Yang, Ruirui1,3; Miao, Ying2; Zhang, Min2; Xi, Yun2; Guo, Rui2; Zheng, Mingyue3; Li, Biao2
刊名BIOORGANIC CHEMISTRY
出版日期2020-03-01
卷号96页码:10
关键词Glyceraldehyde-3-phosphate dehydrogenase Inhibitor Virtual screening Glycolysis Cancer
ISSN号0045-2068
DOI10.1016/j.bioorg.2020.103620
通讯作者Zheng, Mingyue(myzheng@simm.ac.cn) ; Li, Biao(lb10363@rjh.com.cn)
英文摘要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.
WOS关键词KONINGIC ACID ; GENE-EXPRESSION ; DRUG DISCOVERY ; CANCER-CELLS ; GAPDH ; INACTIVATION ; GLIDE ; DNA
资助项目National Natural Science Foundation of China[81871378] ; National Natural Science Foundation of China[81773634] ; Shanghai Key Clinical Project (China) ; Personalized Medicines-Molecular Signaturebased Drug Discovery and Development, Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12050201]
WOS研究方向Biochemistry & Molecular Biology ; Chemistry
语种英语
WOS记录号WOS:000516796900023
出版者ACADEMIC PRESS INC ELSEVIER SCIENCE
源URL[http://119.78.100.183/handle/2S10ELR8/280920]  
专题新药研究国家重点实验室
通讯作者Zheng, Mingyue; Li, Biao
作者单位1.ShanghaiTech Univ, Sch Life Sci & Technol, 393 Huaxiazhong Rd, Shanghai 200031, Peoples R China
2.Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Nucl Med, Sch Med, 197 Ruijin Second Rd, Shanghai 200025, Peoples R China
3.Chinese Acad Sci, Drug Discovery & Design Ctr, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
4.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
推荐引用方式
GB/T 7714		 Li, Ting,Tan, Xiaoqin,Yang, Ruirui,et al. Discovery of novel glyceraldehyde-3-phosphate dehydrogenase inhibitor via docking-based virtual screening[J]. BIOORGANIC CHEMISTRY,2020,96:10.
APA Li, Ting.,Tan, Xiaoqin.,Yang, Ruirui.,Miao, Ying.,Zhang, Min.,...&Li, Biao.(2020).Discovery of novel glyceraldehyde-3-phosphate dehydrogenase inhibitor via docking-based virtual screening.BIOORGANIC CHEMISTRY,96,10.
MLA Li, Ting,et al."Discovery of novel glyceraldehyde-3-phosphate dehydrogenase inhibitor via docking-based virtual screening".BIOORGANIC CHEMISTRY 96(2020):10.

入库方式： OAI收割

来源：上海药物研究所

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