A Novel Inhibitor of the Obesity-Related Protein FTO.

Biochemistry

PubMedID: 26915401

Qiao Y, Zhou B, Zhang M, Liu W, Han Z, Song C, Yu W, Yang Q, Wang R, Wang S, Shi S, Zhao R, Chai J, Chang J. A Novel Inhibitor of the Obesity-Related Protein FTO. Biochemistry. 2016;.
Fe(II) and a-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.