Identification of cell-active lysine specific demethylase 1-selective inhibitors

J Am Chem Soc. 2009 Dec 9;131(48):17536-7. doi: 10.1021/ja907055q.


Lysine specific demethylase 1 (LSD1) plays a key role in the regulation of gene expression by removing the methyl groups from methylated Lys4 of histone H3 (H3K4). Here we report the identification of the first small-molecule LSD1-selective inhibitors. These inhibitors show in vivo H3K4-methylating activity and antiproliferative activity and should be useful as lead structures for anticancer drugs and as tools for studying the biological roles of LSD1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalytic Domain
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Crystallography, X-Ray
  • Drug Design
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology*
  • Histone Demethylases / antagonists & inhibitors*
  • Histone Demethylases / chemistry
  • Histones / metabolism
  • Humans
  • Models, Molecular
  • Substrate Specificity


  • Enzyme Inhibitors
  • Histones
  • Histone Demethylases
  • KDM1A protein, human