Beyond ferrostatin-1 : a comprehensive review of ferroptosis inhibitors

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