Work

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

Year: 2025

Type: article

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. • Novel substitution patterns for 15-LOX-1 inhibitors with an indole scaffold were identified. • The most potent 15-LOX-1 inhibitor 5i exhibited enhanced enzyme inhibition compared with reference inhibitor PD146176. • Compound 5i effectively protected Hek293 cells from RSL3-induced cell death and attenuated lipid peroxidation levels.

Source: European Journal of Medicinal Chemistry

DOI: 10.1016/j.ejmech.2025.117517

Authors: Jianqiu Zhang, Petra E. van der Wouden, Frank J. Dekker

Institution: University of Groningen

Language: English

Topic: Ferroptosis and cancer prognosis

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,650