Introduction: NOD-like receptor family pyrin domain containing 3 (NLRP3) can sense a plethora of exogenous and endogenous dangers. Upon activation, a multimeric protein complex, the NLRP3 inflammasome, is formed to initiate the innate immune responses. Emerging studies have implicated the pathophysiological roles of this protein complex in human disorders, highlighting that it represents a druggable target for therapeutics development.
Areas covered: The current review summarizes the functional facets of the NLRP3 inflammasome, its association with autoimmune diseases, and recent patents on the development of NLRP3 inhibitors. Literature search was conducted using SciFinder and Google Patents with the key word NLRP3 and NLRP3 inhibitors.
Expert opinion: Although significant advances have been made in understanding the NLRP3 inflammasome, more studies are still needed to elucidate the molecular mechanisms underlying its roles in autoimmune diseases. A number of NLRP3 inhibitors have been patented, however, none of them have been approved for clinical use. Due to the complex nature of the NLRP3 inflammasome, novel screening assays along with target engagement methods could benefit the drug discovery and clinical translation. In addition, clinical trials on NLRP3 inhibitors are still in their early stages, and continuous investigations are needed to fully assess their safety and effectiveness.
Keywords: NLRP3 inflammasome; SAR; Therapeutics; autoimmune diseases; small molecule inhibitors.