A Novel Inhibitor of the Obesity-Related Protein FTO

被引：79
|
作者：
Qiao, Yan [1 ]
Zhou, Bin [2 ,3 ]
Zhang, Meizi [4 ]
Liu, Weijia [2 ,3 ]
Han, Zhifu [2 ,3 ]
Song, Chuanjun [5 ]
Yu, Wenquan [5 ]
Yang, Qinghua [5 ]
Wang, Ruiyong [5 ]
Wang, Shaomin [5 ]
Shi, Shuai [5 ]
Zhao, Renbin [4 ]
Chai, Jijie [2 ,3 ]
Chang, Junbiao [1 ]
机构：
[1] Zhengzhou Univ, Basic Med Coll, Dept Pathophysiol, Zhengzhou 450001, Peoples R China
[2] Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China
[3] Tsinghua Peking Ctr Life Sci, Beijing 100084, Peoples R China
[4] China Acad Space Technol, Engn Res Ctr Space Biol, Space Biol Res & Technol Ctr, Beijing 100190, Peoples R China
[5] Zhengzhou Univ, Coll Chem & Mol Engn, Zhengzhou 450001, Peoples R China
来源：
BIOCHEMISTRY | 2016年 / 55卷 / 10期
基金：
中国博士后科学基金; 中国国家自然科学基金;
关键词：
RNA DEMETHYLASE ALKBH5; OXIDATIVE DEMETHYLATION; CRYSTAL-STRUCTURE; FAT-MASS; DNA; N-6-METHYLADENOSINE; 3-METHYLTHYMINE; RECOGNITION; METHYLATION; MECHANISM;
D O I：
10.1021/acs.biochem.6b00023
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Fe-II and alpha-ketoglutarate-dependent fat mass and obesity associated protein (FTO)-dependent demethylation of m(6)A is important for regulation of mRNA splicing and adipogenesis. Developing FTO-specific inhibitors can help probe the biology of FTO and unravel novel therapeutic targets for treatment of obesity or obesity-associated diseases. In the present paper, we have identified that 4-chloro-6-(6'-chloro-7'-hydroxy-2',4',4'-trimethyl-chroman-2'-yl)benzene-1,3-diol (CHTB) is an inhibitor of FTO. The crystal structure of CHTB complexed with human FTO reveals that the novel small molecule binds to FTO in a specific manner. The identification of the novel small molecule offers opportunities for further development of more selective and potent FTO inhibitors.
引用
收藏
页码：1516 / 1522
页数：7
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