Dapansutrile

Dapansutrile (CAS No.: 54863-37-5) is a potent, orally active small-molecule inhibitor of the NLRP3 inflammasome, widely utilized in biomedical research focused on inflammatory and autoinflammatory diseases. It selectively targets NLRP3 signaling by inhibiting inflammasome assembly, including suppression of ASC oligomerization and disruption of NLRP3 interactions with caspase-1, thereby reducing caspase-1 activation and the subsequent maturation and release of pro-inflammatory cytokines such as IL-1β and IL-18 without significantly affecting TNF-α pathways. In vitro studies demonstrate activity in the nanomolar to low micromolar range across macrophages, neutrophils, and human monocyte-derived cells, where it effectively attenuates canonical and non-canonical inflammasome activation. In vivo, Dapansutrile has been shown to reduce inflammatory mediators including IL-1β, IL-6, myeloperoxidase, and chemokines, while modulating oxidative metabolism markers in models of systemic inflammation and crystal-induced arthritis, supporting its role in regulating innate immune responses and metabolic inflammation. Its pharmacological profile makes it a valuable tool for investigating NLRP3-driven pathologies, including gout, cryopyrin-associated syndromes, and cardiovascular or metabolic inflammatory conditions, with experimental dosing and application tailored to specific cellular systems and animal models in drug discovery and mechanistic studies.