典型文献
Discovery of small-molecule activators of nicotinamide phosphoribosyltransferase(NAMPT)and their preclinical neuroprotective activity
文献摘要：
The decline of nicotinamide adenine dinucleotide(NAD)occurs in a variety of human pathologies including neurodegeneration.NAD-boosting agents can provide neuroprotective benefits.Here,we report the discovery and development of a class of potent activators(NATs)of nicotinamide phosphoribosyltransferase(NAMPT),the rate-limiting enzyme in the NAD salvage pathway.We obtained the crystal structure of NAMPT in complex with the NAT,which defined the allosteric action of NAT near the enzyme active site.The optimization of NAT further revealed the critical role of K189 residue in boosting NAMPT activity.NATs effectively increased intracellular levels of NAD and induced subsequent metabolic and transcriptional reprogramming.Importantly,NATs exhibited strong neuroprotective efficacy in a mouse model of chemotherapy-induced peripheral neuropathy(CIPN)without any overt toxicity.These findings demonstrate the potential of NATs in the treatment of neurodegenerative diseases or conditions associated with NAD level decline.
文献关键词：
中图分类号：
作者姓名：
Hong Yao;Minghui Liu;Leibo Wang;Yumeng Zu;Chou Wu;Chenyu Li;Ruoxi Zhang;Haigen Lu;Feifei Li;Shuang Xi;Shuangquan Chen;Xuanyu Gu;Tianya Liu;Jie Cai;Shirong Wang;Maojun Yang;Guo-Gang Xing;Wei Xiong;Lan Hua;Yefeng Tang;Gelin Wang
作者机构：
School of Pharmaceutical Sciences,Beijing Advanced Innovation Center for Structural Biology,Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology,Tsinghua University,Beijing,China;Joint Graduate Program of Peking-Tsinghua-NIBS,School of Life Sciences,Peking University,Beijing,China;Joint Graduate Program of Peking-Tsinghua-NIBS,School of Life Sciences,Tsinghua University,Beijing,China;Tsinghua-Peking Joint Center for Life Sciences,Tsinghua University,Beijing,China;Ministry of Education Key Laboratory of Protein Science,Tsinghua-Peking Joint Center for Life Sciences,Beijing Advanced Innovation Center for Structural Biology,School of Life Sciences,Tsinghua University,Beijing,China;Neuroscience Research Institute,Peking University,Beijing,China;Beijing Advanced Innovation Center for Intelligent Robots and System,Beijing Institute of Technology,Beijing,China;School of Life Sciences,Tsinghua University,Beijing,China;GHDDI,Beijing,China
文献出处：
引用格式：
[1]Hong Yao;Minghui Liu;Leibo Wang;Yumeng Zu;Chou Wu;Chenyu Li;Ruoxi Zhang;Haigen Lu;Feifei Li;Shuang Xi;Shuangquan Chen;Xuanyu Gu;Tianya Liu;Jie Cai;Shirong Wang;Maojun Yang;Guo-Gang Xing;Wei Xiong;Lan Hua;Yefeng Tang;Gelin Wang-.Discovery of small-molecule activators of nicotinamide phosphoribosyltransferase(NAMPT)and their preclinical neuroprotective activity)[J].细胞研究（英文版）,2022(06):570-584
A类：
NATs,K189
B类：
Discovery,small,molecule,activators,nicotinamide,phosphoribosyltransferase,NAMPT,their,preclinical,neuroprotective,activity,decline,adenine,dinucleotide,NAD,occurs,variety,human,pathologies,including,neurodegeneration,boosting,agents,can,provide,benefits,Here,we,report,discovery,development,class,limiting,enzyme,salvage,pathway,We,obtained,crystal,structure,complex,which,defined,allosteric,action,near,active,site,optimization,further,revealed,critical,role,residue,effectively,increased,intracellular,levels,induced,subsequent,metabolic,transcriptional,reprogramming,Importantly,exhibited,strong,efficacy,mouse,model,chemotherapy,peripheral,neuropathy,CIPN,without,any,overt,toxicity,These,findings,demonstrate,potential,treatment,neurodegenerative,diseases,conditions,associated
AB值：
0.611102
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机标中图分类号，由域田数据科技根据网络公开资料自动分析生成，仅供学习研究参考。
