Identification of A Novel Small-Molecule Binding Site of the Fat Mass and Obesity Associated Protein (FTO)

2015/08/28 by Wu He, Bin Zhou, Weijia Liu +16 · 26 citations
Biochemistry, Genetics and Molecular Biology · #RNA modifications and cancer #RNA Research and Splicing #Cancer-related molecular mechanisms research

paper · doi:10.1021/acs.jmedchem.5b00702

Abstract

N-(5-Chloro-2,4-dihydroxyphenyl)-1-phenylcyclobutanecarboxamide (N-CDPCB, 1a) is found to be an inhibitor of the fat mass and obesity associated protein (FTO). The crystal structure of human FTO with 1a reveals a novel binding site for the FTO inhibitor and defines the molecular basis for recognition by FTO of the inhibitor. The identification of the new binding site offers new opportunities for further development of selective and potent inhibitors of FTO, which is expected to provide information concerning novel therapeutic targets for treatment of obesity or obesity-associated diseases.

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