Overview

• Virginia Commonwealth University researchers identified YM81 as a selective blocker of gasdermin D, a key effector of pyroptosis.
• In a small study, five treated mice showed significantly reduced ALT and AST and less liver inflammation compared with ten placebo controls.
• Biophysical assays indicated direct GSDMD binding (KD about 197 nM) and inhibition of IL-1β release across multiple inflammasome pathways (IC50 about 950 nM).
• Investigators describe the program as early stage and plan to improve potency, safety and stability before expanding to additional animal models.
• Acetaminophen overdose is the leading U.S. cause of acute liver injury, and the only approved antidote, N-acetylcysteine, is time-sensitive to roughly eight hours after ingestion.