Small-molecule inhibitors targeting the NLRP3 inflammasome: advances since mid-2023 and future perspectives

The nod-like receptor protein 3 (NLRP3) inflammasome, a critical component of the innate immune system, governs the release of pro-inflammatory cytokines such as interleukin-1β (IL-1β) and IL-18 and thereby plays a central role in the pathogenesis of various inflammatory diseases. Its aberrant activation is closely linked to neurodegenerative disorders, autoimmune diseases, metabolic syndromes, etc., establishing NLRP3 as an attractive target for anti-inflammatory drug discovery. This review summarizes recent advances in NLRP3 inflammasome inhibitors reported from mid-2023 to the beginning of 2026, with emphasis on clinical development status, patent landscapes, and structural classifications. Emerging directions, including the development of NLRP3 degraders via targeted protein degradation (TPD) and the discovery of natural product-derived inhibitors, are also highlighted as growing areas of interest. By providing new perspectives on lead identification, structure-activity relationships (SARs) optimization, mechanistic studies, and clinical translation, this review aims to facilitate the rational design and development of next-generation NLRP3.