A Novel Inhibitor of the Obesity-Related Protein FTO

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• 作者：Yan Qiao ; Bin Zhou ; Meizi Zhang ; Weijia Liu ; Zhifu Han ; Chuanjun Song ; Wenquan Yu ; Qinghua Yang ; Ruiyong Wang ; Shaomin Wang ; Shuai Shi ; Renbin Zhao ; Jijie Chai ; Junbiao Chang
• 刊名：Biochemistry
• 出版年：2016
• 出版时间：March 15, 2016
• 年：2016
• 卷：55
• 期：10
• 页码：1516-1522
• 全文大小：380K
• ISSN：1520-4995

文摘

Fe^II and α-ketoglutarate-dependent fat mass and obesity associated protein (FTO)-dependent demethylation of m⁶A 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.