Identification of selective and reversible LSD1 inhibitors with anti-metastasis activity by high-throughput docking

Bioorg Med Chem Lett. 2019 Feb 15;29(4):544-548. doi: 10.1016/j.bmcl.2018.12.067. Epub 2019 Jan 2.

Abstract

The overexpression of lysine specific demethylase 1 (LSD1) has been reported in various human tumors. There is increasing interest in targeting LSD1 with small molecules for cancer treatment. A released structure of an LSD1 kinase domain in complex with FAD was used to set up a low-cost high-throughput docking protocol for quick identification of LSD1 inhibitors. The most promising hit L05 was confirmed to be a potent, selective and reversible LSD1 inhibitor and displayed marked inhibition of colorectal cells migration without significant cytotoxicity.

Keywords: Anti-migration; Colorectal cancer; High-throughput docking; Inhibitors; LSD1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Demethylation
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Histone Demethylases / antagonists & inhibitors*
  • Histones / chemistry
  • Histones / metabolism
  • Humans
  • Lysine / metabolism
  • Methylation
  • Molecular Docking Simulation
  • Neoplasm Metastasis / prevention & control*
  • Neoplasms / enzymology
  • Neoplasms / pathology
  • Structure-Activity Relationship

Substances

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