Novel 15-lipoxygenase-1 inhibitor protects cells from RSL3-induced cell death

  • Eur J Med Chem. 2025 Jun 5:290:117517. doi: 10.1016/j.ejmech.2025.117517.
Jianqiu Zhang  1 ,  Petra E van der Wouden  1 ,  Frank J Dekker  2
Affiliations
  • 1. Department of Chemical and Pharmaceutical Biology, Groningen,Research Institute of Pharmacy (GRIP), University of Groningen, Antonius Deusinglaan 1, 9713, AV, Groningen, the Netherlands.
  • 2. Department of Chemical and Pharmaceutical Biology, Groningen,Research Institute of Pharmacy (GRIP), University of Groningen, Antonius Deusinglaan 1, 9713, AV, Groningen, the Netherlands. Electronic address: [email protected].
PMID: 40132494 DOI: 10.1016/j.ejmech.2025.117517
Abstract

Ferroptosis is a form of regulated cell death characterized by the accumulation of lipid peroxides. The enzyme 15-lipoxygenase-1 (15-LOX-1) plays a key role in catalyzing the formation of lipid peroxides. Therefore, inhibition of 15-LOX-1 enzyme activity holds promise to decrease the levels of lipid peroxidation. In this study, a novel potent 15-LOX-1 inhibitor, 5i, was developed and structure-activity relationships were explored. In vitro, this inhibitor inhibited lipid peroxidation and protected cells from RSL3-induced cell death. Thus, we report a potent 15-LOX-1 inhibitor, which can be used as a tool to investigate the role of 15-LOX-1.

Keywords
15-lipoxygenase-1 (15-LOX-1); Cell death; Indole; Lipid peroxidation; Lipid peroxides.
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