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Development of Cell-Active N-6-Methyladenosine RNA Demethylase FTO Inhibitor
文献类型：期刊论文
| 作者 | Chen, Baoen2; Ye, Fei2; Yu, Lu1; Jia, Guifang3; Huang, Xiaotian2; Zhang, Xueju2; Peng, Shuying2; Chen, Kai4; Wang, Meining2; Gong, Shouze2 |
| 刊名 | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
 |
| 出版日期 | 2012-10-31 |
| 卷号 | 134期号:43页码:17963-17971 |
| ISSN号 | 0002-7863 |
| DOI | 10.1021/ja3064149 |
| 文献子类 | Article |
| 英文摘要 | The direct nucleic acid repair dioxygenase FTO is an enzyme that demethylates N-6-methyladenosine (m(6)A) residues in mRNA in vitro and inside cells. FTO is the first RNA demethylase discovered that also serves a major regulatory function in mammals. Together with structure-based virtual screening and biochemical analyses, we report the first identification of several small-molecule inhibitors of human FTO demethylase. The most potent compound, the natural product rhein, which is neither a structural mimic of 2-oxoglutarate nor a chelator of metal ion, competitively binds to the FTO active site in vitro. Rhein also exhibits good inhibitory activity on m(6)A demethylation inside cells. These studies shed light on the development of powerful probes and new therapies for use in RNA biology and drug discovery. |
| WOS关键词 | NUCLEIC-ACID DEMETHYLASE ; OBESITY-ASSOCIATED FTO ; REPAIR ENZYME ALKB ; OXIDATIVE DEMETHYLATION ; CRYSTAL-STRUCTURES ; MASS-SPECTROMETRY ; ESCHERICHIA-COLI ; COMMON VARIANT ; ADULT OBESITY ; FAT MASS |
| 资助项目 | Chinese Academy of Sciences (the Hundred Talent Program)[XDA01040305] ; National Natural Science Foundation of China[20972173] ; National Natural Science Foundation of China[90913010] ; National Natural Science Foundation of China[20972174] ; National Natural Science Foundation of China[21021063] ; National Natural Science Foundation of China[91029704] ; National Natural Science Foundation of China[21210003] ; Hi-Tech Research and Development Program of China[2012AA020302] ; State Key Program of Basic Research of China Grant[2009CB918502] ; Computer Network Information Center[00000000] ; Chinese Academy of Sciences[00000000] ; Shanghai Supercomputing Center[00000000] |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000310483500025 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277901]  |
| 专题 | 药物发现与设计中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 药理学第三研究室 |
| 通讯作者 | Luo, Cheng |
| 作者单位 | 1.Shenyang Pharmaceut Univ, Shenyang 110016, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 3.Peking Univ, Coll Chem & Mol Engn, Beijing 100871, Peoples R China; 4.Univ Chicago, Dept Chem, Chicago, IL 60637 USA; 5.Lanzhou Univ, State Key Lab Appl Organ Chem, Lanzhou 730000, Peoples R China |
| 推荐引用方式 GB/T 7714 | Chen, Baoen,Ye, Fei,Yu, Lu,et al. Development of Cell-Active N-6-Methyladenosine RNA Demethylase FTO Inhibitor[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,2012,134(43):17963-17971. |
| APA | Chen, Baoen.,Ye, Fei.,Yu, Lu.,Jia, Guifang.,Huang, Xiaotian.,...&Yang, Cai-Guang.(2012).Development of Cell-Active N-6-Methyladenosine RNA Demethylase FTO Inhibitor.JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,134(43),17963-17971. |
| MLA | Chen, Baoen,et al."Development of Cell-Active N-6-Methyladenosine RNA Demethylase FTO Inhibitor".JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 134.43(2012):17963-17971. |
入库方式： OAI收割
来源：上海药物研究所
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