Beyond ferrostatin-1: a comprehensive review of ferroptosis inhibitors.

Trends Pharmacol Sci

Laboratory of Medicinal Chemistry, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, 2610 Antwerp, Belgium. Electronic address:

Published: December 2023

AI Article Synopsis

  • Ferroptosis is a type of cell death driven by iron and the peroxidation of phospholipids in cell membranes.
  • Ferrostatin 1 is a key synthetic antioxidant that prevents ferroptosis and serves as a standard reference compound in research.
  • The review discusses various classes of ferroptosis inhibitors, including both natural and synthetic antioxidants, analyzing their chemical properties, effectiveness, and potential for use in living organisms.

Article Abstract

Ferroptosis is an iron-catalysed form of regulated cell death, which is critically dependent on phospholipid peroxidation of cellular membranes. Ferrostatin 1 was one of the first synthetic radical-trapping antioxidants (RTAs) reported to block ferroptosis and it is widely used as reference compound. Ferroptosis has been linked to multiple diseases and the use of its inhibitors could have therapeutic potential. Although, novel biochemical pathways provide insights for different pharmacological targets, the use of lipophilic RTAs to block ferroptosis remains superior. In this Review, we provide a comprehensive overview of the different classes of ferroptosis inhibitors, focusing on endogenous and synthetic RTAs. A thorough analysis of their chemical, pharmacokinetic, and pharmacological properties and potential for in vivo use is provided.

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http://dx.doi.org/10.1016/j.tips.2023.08.012DOI Listing

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