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Cutting-edge methods for recombinant selenoprotein production have enabled an astonishing discovery by the Arnér group at Karolinska Institutet in Stockholm. By utilizing high quality selenoproteins, with specific activity very close to that of native enzymes, the group successfully established a comprehensive screen for inhibitors of human glutathione peroxidases. Their research unveiled a startling revelation: the ferroptosis inducing compounds RSL3 and ML162 do not directly inhibit GPX4 as previously thought, but instead target thioredoxin reductase. Additionally, the team made significant headway by discovering novel inhibitors of GPX1 and GPX4. These findings not only challenge our current understanding of ferroptosis mechanisms but also pave the way for new venues of research in the field and innovation within the Life Science industry.
The researchers highlighted that the findings would not have been possible without access to the highest quality selenoproteins with specific activity close to that of native enzymes. The proteins and screen were enabled by Selenozyme’s unique production method. We are the world’s first company specialized for production of recombinant selenoproteins and no other vendor can provide the same wide range of products with as high quality and detailed characterization.
The ferroptosis inducing compounds RSL3 and ML162 are not direct inhibitors of GPX4 but of TXNRD1.
Cheff DM, et al. Redox Biol. 2023.PMID: 37087975 Free PMC article.
Development of an assay pipeline for the discovery of novel small molecule inhibitors of human glutathione peroxidases GPX1 and GPX4.
Cheff DM, et al. Redox Biol. 2023.PMID: 37244126 Free PMC article.