The simultaneous inhibition of these two regulated cell death pathways represents a highly innovative approach that could treat severe and chronic diseases.
SeaBeLife is thrilled to share the publication of an article in Cell Death Discovery journal, part of Nature publications, on its patented molecule action mechanism, titled ‘Sibiriline, a novel dual inhibitor of necroptosis and ferroptosis, prevents RIPK1 kinase activity and (phospho)lipid peroxidation as a potential therapeutic strategy’.
In this article, our co-founders Claire Delehouzé, Morgane Rousselot, Stéphane Bach and Marie-Thérèse Dimanche-Boitrel, along with Axelle Autret, Romain Lucas and fellow authors, prove that sibiriline uniquely targets and inhibits two key forms of programmed cell death: necroptosis and ferroptosis.
Sibiriline shows in vitro efficacy in cellular models of Parkinson’s disease and cystic fibrosis, highlighting its potential as a multi-target therapeutic molecule. It works by inhibition of both RIPK1 kinase and (phospho)lipid peroxidation. The findings shed light on the high therapeutic potency of RIPK1 inhibitors with RTA activity and the potential for sibiriline to contribute to advancements in understanding cellular death mechanisms, which are closely linked to degenerative and inflammatory diseases.
Sibiriline acts by suppressing RIPK1 kinase activity, a critical signaling protein implicated in necroptosis. By directly inhibiting RIPK1 kinase, sibiriline prevents the spiral of events that typically culminate in cell death.
Beyond its impact on necroptosis, sibiriline can also inhibit ferroptosis, an iron-dependent form of cell death characterized by phospholipid peroxidation. Ferroptosis is believed to be central in neurodegenerative disorders, organ failures and cancer. The compound’s dual action sets it apart from other treatments that typically target only one pathway.
The research team behind the study employed cutting-edge cell models to simulate inflammatory and oxidative stress conditions to validate sibiriline’s protective activity. Treated cells displayed clear resistance to deadly stimuli that would otherwise induce necroptosis or ferroptosis, highlighting the compound’s therapeutic potential.
Sibiriline’s high selectivity could be a breakthrough in drug design, enabling precise inhibition of pathological cell death pathways while still preserving cellular functions. The discovery of sibiriline has been welcomed by experts as an important step, triggering hope for the discovery of new treatments in diseases such as myocardial infarction, Alzheimer’s, Parkinson’s and certain cancers.
This article strongly supports our R&D strategy as we prepare for clinical trials, planned for 2027, to fully demonstrate sibiriline’s pharmacodynamics, long-term safety and efficacy in humans.
Thanks to our innovative technological platform of patented molecules, we are focusing our efforts on two flagship programs, in dry AMD and severe acute hepatitis, two high medical need indications.
Read the full article:
https://www.nature.com/articles/s41420-025-02852-8
Find additional information in this ScienMag article:
https://scienmag.com/sibiriline-blocks-necroptosis-and-ferroptosis-simultaneously/