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Quantitative High-Throughput Screening Identifies 8-Hydroxyquinolines as Cell-Active Histone Demethylase Inhibitors
DOI:
10.1371/journal.pone.0015535
PMID:
21124847
Authors:
Oliver
King
(University of Oxford)
,
Xuan Shirley
LI
,
Masaaki
Sakurai
,
Akane
Kawamura
,
Nathan
Rose
(University of Oxford)
,
Stanley
Ng
(University of Oxford)
,
Amy
Quinn
,
Ganesha
Rai
,
Bryan
Mott
,
Paul
Beswick
,
Robert
Klose
,
Udo
Oppermann
,
Ajit
Jadhav
,
Tom
Heightman
,
David
Maloney
,
Christopher
Schofield
,
Anton
Simeonov
Co-authored by industrial partner:
No
Type:
Journal Paper
Journal:
PLoS One
State:
Published (Approved)
Published:
November 2010

Abstract: Small molecule modulators of epigenetic processes are currently sought as basic probes for biochemical mechanisms, and as starting points for development of therapeutic agents. N (epsilon)-Methylation of lysine residues on histone tails is one of a number of post-translational modifications that together enable transcriptional regulation. Histone lysine demethylases antagonize the action of histone methyltransferases in a site- and methylation state-specific manner. N (epsilon)-Methyllysine demethylases that use 2-oxoglutarate as co-factor are associated with diverse human diseases, including cancer, inflammation and X-linked mental retardation; they are proposed as targets for the therapeutic modulation of transcription. There are few reports on the identification of templates that are amenable to development as potent inhibitors in vivo and large diverse collections have yet to be exploited for the discovery of demethylase inhibitors.
Journal Keywords: Dose-Response; Drug ; Drug; Preclinical ; Enzyme; HeLa; Histones ; Humans ; Hydroxyquinolines ; Jumonji; Lysine ; Mass; Methylation ; Molecular Structure
Subject Areas:
Biology and Bio-materials
Instruments:
I04-Macromolecular Crystallography
Added On:
30/11/2010 08:33
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