Apomorphine is a novel necroptosis inhibitor targeting mixed lineage kinase domain-like protein oligomerization.

ABSTRACT: Necroptosis, a form of programmed cell death, has emerged as a promising therapeutic target. Although several RIPK1 inhibitors have demonstrated favorable safety profiles in clinical trials, clinical translation of necroptosis-targeted therapies remains limited by modest efficacy, limited specificity, and species-specific activity of compounds such as necrosulfonamide (NSA). To resolve these challenges, this study identified a potential necroptosis inhibitor from a clinical drug library. Apomorphine (APO), a non-addictive morphine derivative used to treat Parkinson's disease, was found to inhibit necroptosis by sterically blocking key residues involved in mixed lineage kinase domain-like protein (MLKL) activation and oligomerization, as confirmed by nuclear magnetic resonance analysis. APO

SUBMITTER: Han M 

PROVIDER: S-EPMC12518639 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature