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(-)-Epigallocatechin Gallate is a Noncompetitive Inhibitor of NAD Kinase

文献类型：期刊论文

作者Liu, Tonghai4,5,6; Shi, Wenjia3; Ding, Yiluan5; Wu, Qiqi3; Zhang, Bei4,5; Zhang, Naixia5; Wang, Mingliang2; Du, Daohai5; Zhang, Hao5; Han, Bo1
刊名ACS MEDICINAL CHEMISTRY LETTERS
出版日期2022-10-31
页码8
关键词NAD kinase inhibitor (-)-epigallocatechin gallate hydrogen-deuterium exchange mass spectrometry KRAS
ISSN号1948-5875
DOI10.1021/acsmedchemlett.2c00163
通讯作者Zheng, Jie(jzheng@simm.ac.cn) ; Li, Qi(qf.1007@163.com) ; Luo, Cheng(cluo@simm.ac.cn)
英文摘要Nicotinamide adenine dinucleotide kinase (NADK) controls the intracellular NADPH content and provides reducing power for the synthesis of macromolecules and anti-ROS. Moreover, NADK is considered to be a synthetic lethal gene for KRAS mutations. To discover NADK-targeted probes, a high-throughput screening assay was established and optimized with a Z factor of 0.71. The natural product (-)-epigallocatechin gallate (EGCG) was found to be a noncompetitive inhibitor of NADK with Ki = 3.28 +/- 0.32 mu Mu. The direct binding of EGCG to NADK was determined by several biophysical methods, including NMR spectroscopy, surface plasmon resonance (SPR) assay, and hydrogen-deuterium exchange mass spectrometry (HDX-MS). The SPR assay showed a Kd of 1.78 +/- 1.15 mu Mu. The HDX-MS experiment showed that EGCG was bound at the non-substrate-binding sites of NADK. Besides, binding mode prediction and derivative activity analysis revealed a potential structure-activity relationship between EGCG and NADK. Furthermore, EGCG can specifically inhibit the proliferation of KRAS-mutated lung cancer cell lines without affecting KRAS wild-type lung cancer cell lines.
WOS关键词CELL-GROWTH ; EGCG ; ANALOGS ; TARGET ; DEATH ; POOL
资助项目National Key R&D Program of China[2022YFC3400500] ; National Key R&D Program of China[2021ZD0203900] ; National Natural Science Foundation of China[32000915] ; National Natural Science Foundation of China[81821005] ; National Natural Science Foundation of China[91853205] ; National Multidisciplinary Innovation Team of Traditional Chinese Medicine - National Administration of Traditional Chinese Medicine[ZYYCXTD-202004] ; High-level new Ramp;D institute of Guangdong Province[2019B090904008] ; High-level Innovative Research Institute Guangdong Province[2021B0909050003] ; Guangdong Basic and Applied Basic Research Foundation, Department of Science and Technology of Guangdong Province, Zhongshan Municipal Bureau of Science and Technology
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000879975000001
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/302915]  
专题新药研究国家重点实验室
通讯作者Zheng, Jie; Li, Qi; Luo, Cheng
作者单位1.Shihezi Univ, Sch Pharm, Key Lab Xinjiang Phytomed Resource & Utilizat, Minist Educ, Shihezi 832003, Peoples R China
2.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528437, Peoples R China
3.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China
4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
6.UCAS, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China
推荐引用方式
GB/T 7714		 Liu, Tonghai,Shi, Wenjia,Ding, Yiluan,et al. (-)-Epigallocatechin Gallate is a Noncompetitive Inhibitor of NAD Kinase[J]. ACS MEDICINAL CHEMISTRY LETTERS,2022:8.
APA Liu, Tonghai.,Shi, Wenjia.,Ding, Yiluan.,Wu, Qiqi.,Zhang, Bei.,...&Luo, Cheng.(2022).(-)-Epigallocatechin Gallate is a Noncompetitive Inhibitor of NAD Kinase.ACS MEDICINAL CHEMISTRY LETTERS,8.
MLA Liu, Tonghai,et al."(-)-Epigallocatechin Gallate is a Noncompetitive Inhibitor of NAD Kinase".ACS MEDICINAL CHEMISTRY LETTERS (2022):8.

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来源：上海药物研究所

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