Document Detail


Development of Cell-active N6-Methyladenosine RNA Demethylase FTO Inhibitor.
MedLine Citation:
PMID:  23045983     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The direct nucleic acid repair dioxygenase FTO is an enzyme that demethylates N6-methyladenosine (m6A) residues in mRNA in vitro and inside cells. FTO is the first RNA demethylase discovered that also serves a major regulatory function in mammals. Together with structure-based virtual screening and biochemical analyses, we report the first identification of several small-molecule inhibitors of human FTO demethylase. The most potent compound, the natural product rhein, which is neither a structural mimic of α-ketoglutarate nor a chelator of metal ion, competitively binds to the FTO active site in vitro. Rhein also exhibits good inhibitory activity on m6A demethylation inside cells. These studies shed light on the development of powerful probes and new therapies for use in RNA biology and drug discovery.
Authors:
Baoen Chen; Fei Ye; Lu Yu; Guifang Jia; Xiaotian Huang; Xueju Zhang; Shuying Peng; Kai Chen; Meining Wang; Shouze Gong; Ruihan Zhang; Jinya Yin; Hai-Yan Li; Yiming Yang; Hong Liu; Jiwen Zhang; Hai Yan Zhang; Ao Zhang; Hualiang Jiang; Cheng Luo; Cai-Guang Yang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-9
Journal Detail:
Title:  Journal of the American Chemical Society     Volume:  -     ISSN:  1520-5126     ISO Abbreviation:  J. Am. Chem. Soc.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7503056     Medline TA:  J Am Chem Soc     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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