The ferroptosis inducing compounds RSL3 and ML162 are not direct inhibitors of GPX4 but of TXNRD1

Cheff, Dorian M.; Huang, Chuying; Scholzen, Karoline; Gencheva, Radosveta; Ronzetti, Michael; Cheng, Qing; Hall, Matthew D.; Arnér, Elias S.J.

doi:10.1016/j.redox.2023.102703

articleRedox BiologyApr 17, 2023GOLD OA

The ferroptosis inducing compounds RSL3 and ML162 are not direct inhibitors of GPX4 but of TXNRD1

DMDorian M. Cheff CHChuying Huang KSKaroline Scholzen RGRadosveta Gencheva MRMichael Ronzetti

National Institutes of Health · Karolinska Institutet · +2 more institutions

PubMed

Indexed incrossrefdoajpubmed

Abstract

Ferroptosis is defined as cell death triggered by iron-dependent lipid peroxidation that is preventable by antioxidant compounds such as ferrostatin-1. Endogenous suppressors of ferroptosis include FSP-1 and the selenoprotein GPX4, the latter of which directly enzymatically reduces lipid hydroperoxides. Small molecules that trigger ferroptosis include RSL3, ML162, and ML210; these compounds are often used in studies of ferroptosis and are generally considered as GPX4 inhibitors. Here, we found that RSL3 and ML162 completely lack capacity of inhibiting the enzymatic activity of recombinant selenoprotein GPX4. Surprisingly, these compounds were instead found to be efficient inhibitors of another selenoprotein,…

Citation impact

239

total citations

FWCI: 57.78
Percentile: 100%
References: 42

Citations per year

Authors

8

Topics & keywords

Topics

Keywords

GPX4
Selenoprotein
Programmed cell death
Lipid peroxidation
Context (archaeology)
Chemistry
Enzyme
Biochemistry

UN Sustainable Development Goals

Good health and well-being

No related works found for this paper.