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Plant growth regulator daminozide is a selective inhibitor of human KDM2/7 histone demethylases.

Abstract：

:The JmjC oxygenases catalyze the N-demethylation of N(ε)-methyl lysine residues in histones and are current therapeutic targets. A set of human 2-oxoglutarate analogues were screened using a unified assay platform for JmjC demethylases and related oxygenases. Results led to the finding that daminozide (N-(dimethylamino)succinamic acid, 160 Da), a plant growth regulator, selectively inhibits the KDM2/7 JmjC subfamily. Kinetic and crystallographic studies reveal that daminozide chelates the active site metal via its hydrazide carbonyl and dimethylamino groups.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Rose NR,Woon EC,Tumber A,Walport LJ,Chowdhury R,Li XS,King ON,Lejeune C,Ng SS,Krojer T,Chan MC,Rydzik AM,Hopkinson RJ,Che KH,Daniel M,Strain-Damerell C,Gileadi C,Kochan G,Leung IK,Dunford J,Yeoh KK,Ratcliffe PJ

doi

10.1021/jm300677j

subject

Has Abstract

pub_date

2012-07-26 00:00:00

pages

6639-43

issue

14

eissn

0022-2623

issn

1520-4804

journal_volume

55

pub_type

杂志文章

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