Identification of the KDM2/7 histone lysine demethylase subfamily inhibitor and its antiproliferative activity

J Med Chem. 2013 Sep 26;56(18):7222-31. doi: 10.1021/jm400624b. Epub 2013 Sep 5.


Histone N(ε)-methyl lysine demethylases KDM2/7 have been identified as potential targets for cancer therapies. On the basis of the crystal structure of KDM7B, we designed and prepared a series of hydroxamate analogues bearing an alkyl chain. Enzyme assays revealed that compound 9 potently inhibits KDM2A, KDM7A, and KDM7B, with IC50s of 6.8, 0.2, and 1.2 μM, respectively. While inhibitors of KDM4s did not show any effect on cancer cells tested, the KDM2/7-subfamily inhibitor 9 exerted antiproliferative activity, indicating the potential for KDM2/7 inhibitors as anticancer agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Catalytic Domain
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / pharmacology*
  • Histone Demethylases / antagonists & inhibitors*
  • Histone Demethylases / chemistry
  • Humans
  • Inhibitory Concentration 50
  • Models, Molecular


  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Histone Demethylases