LSD1: biologic roles and therapeutic targeting

Epigenomics. 2016 Aug;8(8):1103-16. doi: 10.2217/epi-2016-0009. Epub 2016 Aug 1.

Abstract

LSD1 (KDM1A; BHC110; AOF2) was the first protein reported to exhibit histone demethylase activity and has since been shown to have multiple essential roles in mammalian biology. Given its enzymatic activity and its high-level expression in many human malignancies, a significant recent focus has been the development of pharmacologic inhibitors. Here we summarize structural and biochemical knowledge of this important epigenetic regulator, with a particular emphasis on the functional and preclinical studies in oncology that have provided justification for the evaluation of tranylcypromine derivative LSD1 inhibitors in early phase clinical trials.

Keywords: GSK2879552; LSD1; ORY1001; acute myeloid leukemia; histone demethylase; small-cell lung cancer.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use
  • Epigenesis, Genetic / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Histone Demethylases / antagonists & inhibitors*
  • Histone Demethylases / chemistry
  • Histone Demethylases / genetics
  • Histone Demethylases / metabolism
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / genetics
  • Molecular Targeted Therapy / methods

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Histone Demethylases
  • KDM1A protein, human