Ferrostatins inhibit oxidative lipid damage and cell death in diverse disease models

J Am Chem Soc. 2014 Mar 26;136(12):4551-6. doi: 10.1021/ja411006a. Epub 2014 Mar 14.


Ferrostatin-1 (Fer-1) inhibits ferroptosis, a form of regulated, oxidative, nonapoptotic cell death. We found that Fer-1 inhibited cell death in cellular models of Huntington's disease (HD), periventricular leukomalacia (PVL), and kidney dysfunction; Fer-1 inhibited lipid peroxidation, but not mitochondrial reactive oxygen species formation or lysosomal membrane permeability. We developed a mechanistic model to explain the activity of Fer-1, which guided the development of ferrostatins with improved properties. These studies suggest numerous therapeutic uses for ferrostatins, and that lipid peroxidation mediates diverse disease phenotypes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Death / drug effects
  • Cyclohexylamines / pharmacology*
  • Cyclohexylamines / therapeutic use
  • Huntington Disease / drug therapy*
  • Huntington Disease / metabolism
  • Huntington Disease / pathology
  • Kidney Diseases / drug therapy*
  • Kidney Diseases / metabolism
  • Kidney Diseases / pathology
  • Leukomalacia, Periventricular / drug therapy*
  • Leukomalacia, Periventricular / metabolism
  • Leukomalacia, Periventricular / pathology
  • Lipid Peroxidation / drug effects
  • Membrane Lipids / metabolism*
  • Oxidation-Reduction / drug effects
  • Phenylenediamines / pharmacology*
  • Phenylenediamines / therapeutic use


  • Cyclohexylamines
  • Membrane Lipids
  • Phenylenediamines
  • ferrostatin-1