中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 新药研究国家重点实验室
Making Protein Degradation Visible: Discovery of Theranostic PROTACs for Detecting and Degrading NAMPT

文献类型：期刊论文

作者Cheng, Junfei2; He, Shipeng3; Xu, Jun1; Huang, Min1; Dong, Guoqiang2; Sheng, Chunquan2
刊名JOURNAL OF MEDICINAL CHEMISTRY
出版日期2022-11-28
页码13
ISSN号0022-2623
DOI10.1021/acs.jmedchem.2c01243
通讯作者Dong, Guoqiang(gdong@smmu.edu.cn) ; Sheng, Chunquan(shengcq@smmu.edu.cn)
英文摘要Proteolysis-targeting chimera (PROTAC) is emerging as a promising technology in targeted protein degradation and drug discovery. However, there is still a lack of effective chemical tools to real-time detect and track the protein degradation. Herein, the first fluorescent and theranostic PROTACs were designed for imaging the degradation of nicotinamide phosphoribosyltransferase (NAMPT) in living cells. Compound B4 was proven to be an environmentally sensitive fluorescent PROTAC, which efficiently degraded NAMPT (DC50 = 8.4 nM) and enabled the visualization of degradation in A2780 cells. As a theranostic agent, PROTAC B4 led to significant reduction of nicotinamide adenine dinucleotide (NAD(+)) and exerted potent antitumor activities both in vitro and in vivo. Collectively, this proof-of-concept study provides a new strategy for the real-time visualization of the process of protein degradation and the improvement of diagnosis and therapeutic efficacy of PROTACs.
WOS关键词NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE NAMPT ; INHIBITORS ; METABOLISM ; TARGET
资助项目National Natural Science Foundation of China ; National Key Research and Development Program of China ; Shanghai Rising-Star Program ; [82030105] ; [81725020] ; [2020YFA0509200] ; [20QA1411700]
WOS研究方向Pharmacology & Pharmacy
语种英语
出版者AMER CHEMICAL SOC
WOS记录号WOS:000891373400001
源URL[http://119.78.100.183/handle/2S10ELR8/304422]  
专题新药研究国家重点实验室
通讯作者Dong, Guoqiang; Sheng, Chunquan
作者单位1.Univ Chinese Acad Sci, Shanghai Inst Mat Med, Chinese Acad Sci, State Key Lab Drug Res, Shanghai 201203, Peoples R China
2.Second Mil Med Univ, Navy Med Univ, Sch Pharm, Shanghai 200433, Peoples R China
3.Shanghai Univ, Inst Translat Med, Shanghai 200444, Peoples R China
推荐引用方式
GB/T 7714		 Cheng, Junfei,He, Shipeng,Xu, Jun,et al. Making Protein Degradation Visible: Discovery of Theranostic PROTACs for Detecting and Degrading NAMPT[J]. JOURNAL OF MEDICINAL CHEMISTRY,2022:13.
APA Cheng, Junfei,He, Shipeng,Xu, Jun,Huang, Min,Dong, Guoqiang,&Sheng, Chunquan.(2022).Making Protein Degradation Visible: Discovery of Theranostic PROTACs for Detecting and Degrading NAMPT.JOURNAL OF MEDICINAL CHEMISTRY,13.
MLA Cheng, Junfei,et al."Making Protein Degradation Visible: Discovery of Theranostic PROTACs for Detecting and Degrading NAMPT".JOURNAL OF MEDICINAL CHEMISTRY (2022):13.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。