Sibiriline, a novel dual inhibitor of necroptosis and ferroptosis, prevents RIPK1 kinase activity and (phospho)lipid peroxidation as a potential therapeutic strategy.

ABSTRACT: In the past two decades, various non-apoptotic pathways of regulated cell death have been identified; a small subset of these, including necroptosis and ferroptosis, manifests the phenotypic features of necrotic death. These two regulated necroses are being extensively studied because of their putative roles in severe acute and chronic pathologies. Moreover, as these regulated necrotic pathways are coactivated in a number of common pathologies, the development of multi-target directed ligands (that is, the use of a polypharmacological strategy) is a path-breaking avenue of research. In this study, we determined that the 7-azaindole derivative, sibiriline, inhibited both RIPK1-driven necroptosis (induced by Tumor Necrosis Factor-α) and ferroptosis (triggered by various classes of ferroptosi

SUBMITTER: Delehouze C 

PROVIDER: S-EPMC12663298 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature