A Novel Inhibitor of the Obesity-Related Protein FTO

作者：Qiao, Yan; Zhou, Bin; Zhang, Meizi; Liu, Weijia; Han, Zhifu; Song, Chuanjun; Yu, Wenquan; Yang, Qinghua; Wang, Ruiyong; Wang, Shaomin; Shi, Shuai; Zhao, Renbin; Chai, Jijie^*; Chang, Junbiao^*

来源：Biochemistry, 2016, 55(10): 1516-1522.

DOI：10.1021/acs.biochem.6b00023

• RNA DEMETHYLASE ALKBH5
• OXIDATIVE DEMETHYLATION
• CRYSTAL-STRUCTURE
• FAT-MASS
• DNA
• N-6-METHYLADENOSINE
• 3-METHYLTHYMINE
• RECOGNITION
• METHYLATION
• MECHANISM

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.

• 出版日期2016-3-15
• 单位清华大学; 中国空间技术研究院; 郑州大学