A Novel Inhibitor of the Obesity-Related Protein FTO

被引：80

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

页码：1516 / 1522

页数：7

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