2. Academic Validation
  3. A selective inhibitor and probe of the cellular functions of Jumonji C domain-containing histone demethylases

A selective inhibitor and probe of the cellular functions of Jumonji C domain-containing histone demethylases

  • J Am Chem Soc. 2011 Jun 22;133(24):9451-6. doi: 10.1021/ja201597b.
Xuelai Luo 1,  Yongxiang Liu,  Stefan Kubicek,  Johanna Myllyharju,  Anthony Tumber,  Stanley Ng,  Ka Hing Che,  Jessica Podoll,  Tom D Heightman,  Udo Oppermann,  Stuart L Schreiber,  Xiang Wang
Affiliations

Affiliation

  • 1 Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309, USA.
PMID: 21585201 DOI: 10.1021/ja201597b
Abstract

Histone methylations are important chromatin marks that regulate gene expression, genomic stability, DNA repair, and genomic imprinting. Histone demethylases are the most recent family of histone-modifying enzymes discovered. Here, we report the characterization of a small-molecule inhibitor of Jumonji C domain-containing histone demethylases. The inhibitor derives from a structure-based design and preferentially inhibits the subfamily of trimethyl lysine demethylases. Its methyl ester prodrug, methylstat, selectively inhibits Jumonji C domain-containing his-tone demethylases in cells and may be a useful small-molecule probe of chromatin and its role in Epigenetics.

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