PANoptosis as a drug discovery framework: integrating cell death architecture with clinical translation - PubMed
9 hours ago
- #cell death
- #PANoptosis
- #drug discovery
- PANoptosis is a unified inflammatory cell death program integrating apoptosis, pyroptosis, and necroptosis.
- It is orchestrated by supramolecular PANoptosome complexes involving sensors, adaptors, and executioners.
- PANoptosis acts as a defense mechanism against pathogens and oncogenic stress but can also drive immunopathology in diseases like sepsis, cancer, and neurodegeneration.
- The review discusses molecular architecture, cross-regulatory redundancies, and post-translational checkpoints for therapeutic intervention.
- Pharmacological interventions include small-molecule inhibitors, biologics, and nucleic acid therapeutics, with ongoing clinical trials.
- The Clinical Polarity and Timing Model guides when to induce or restrain PANoptosis based on disease context.
- Emerging biomarker panels aid in patient stratification and pharmacodynamic monitoring.
- Future drug discovery focuses on covalent GSDMD antagonists, CNS-penetrant RIPK1 inhibitors, and synthetic biology approaches.
- PANoptosis presents a therapeutic target and adjuvant framework for infectious, inflammatory, oncologic, and neurodegenerative diseases.