Gasdermin D pores enable targeted caspase delivery to halt pyroptosis

Researchers describe covalent caspase inhibitors that selectively block pyroptosis and IL-1β/IL-18 secretion while remaining excluded from healthy cells. These inhibitors are taken up through Gasdermin D–formed pores during pyroptosis, preventing caspase-1/-11-driven inflammation without triggering apoptosis. In a mouse model of endotoxic shock, inhibition of caspase-1/-11 reduced inflammatory cytokines, demonstrating a potential therapeutic strategy that exploits GSDMD pores for targeted caspase inhibition in inflammatory diseases.