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

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.