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

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

  • J Med Chem. 2012 Jul 26;55(14):6639-43. doi: 10.1021/jm300677j.
Nathan R Rose 1,  Esther C Y Woon,  Anthony Tumber,  Louise J Walport,  Rasheduzzaman Chowdhury,  Xuan Shirley Li,  Oliver N F King,  Clarisse Lejeune,  Stanley S Ng,  Tobias Krojer,  Mun Chiang Chan,  Anna M Rydzik,  Richard J Hopkinson,  Ka Hing Che,  Michelle Daniel,  Claire Strain-Damerell,  Carina Gileadi,  Grazyna Kochan,  Ivanhoe K H Leung,  James Dunford,  Kar Kheng Yeoh,  Peter J Ratcliffe,  Nicola Burgess-Brown,  Frank von Delft,  Susanne Muller,  Brian Marsden,  Paul E Brennan,  Michael A McDonough,  Udo Oppermann,  Robert J Klose,  Christopher J Schofield,  Akane Kawamura
Affiliations

Affiliation

  • 1 Epigenetic Regulation of Chromatin Function Group, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, U.K.
PMID: 22724510 DOI: 10.1021/jm300677j
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.

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