[Cell Death Discovery] Sibiriline, a novel dual inhibitor of necroptosis and ferroptosis, prevents RIPK1 kinase activity and (phospho)lipid peroxidation as a potential therapeutic strategy

Crédit photo Axelle Autret (SeaBeLife Biotech). 

In this study, we show that the molecule Sibiriline can simultaneously inhibit necroptosis and ferroptosis, two forms of regulated cell death involved in numerous pathologies. We demonstrate that it specifically blocks RIPK1 activity and inhibits lipid peroxidation through its antioxidant properties. We propose naming this class of compounds the “RIPROStatins”.  We also show its in vitro efficacy in cellular models of Parkinson’s disease and cystic fibrosis. 

Overall, these results position Sibiriline as a promising therapeutic molecule thanks to its multi-target mode of action.

Read the publication : https://www.nature.com/articles/s41420-025-02852-8

Delehouzé, C., Mallais, M., Comte, A. et al. Sibiriline, a novel dual inhibitor of necroptosis and ferroptosis, prevents RIPK1 kinase activity and (phospho)lipid peroxidation as a potential therapeutic strategy. Cell Death Discov. 11, 552 (2025). https://doi.org/10.1038/s41420-025-02852-8