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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3-L1 Cells
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Alpha-Ketoglutarate-Dependent Dioxygenase FTO
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Aminophenols / chemical synthesis
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Aminophenols / chemistry*
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Aminophenols / pharmacology
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Anilides / chemical synthesis
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Anilides / chemistry*
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Anilides / pharmacology
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Animals
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Binding Sites
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Crystallography, X-Ray
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Databases, Chemical
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Humans
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Methylation
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Mice
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Models, Molecular
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Protein Binding
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Proteins / antagonists & inhibitors*
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Proteins / chemistry
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RNA / chemistry
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RNA, Messenger / metabolism
Substances
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Aminophenols
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Anilides
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N-(5-chloro-2,4-dihydroxyphenyl)-1-phenylcyclobutanecarboxamide
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Proteins
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RNA, Messenger
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RNA
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Alpha-Ketoglutarate-Dependent Dioxygenase FTO
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FTO protein, human