The research progression of direct NLRP3 inhibitors to treat inflammatory disorders

Abstract

The NLRP3 inflammasome represents a cytoplasmic multiprotein complex with the capability to recognize a wide range of pathogen-derived, environmental, and endogenous stress-related factors. Dysregulated activation of the NLRP3 inflammasome has been implicated in the development of various inflammasome-associated disorders, highlighting its significance as a pivotal target for the treatment of inflammatory diseases. Nonetheless, despite its clinical importance, there is currently a lack of specific drugs available for directly targeting the NLRP3 inflammasome. Several strategies have been explored to target different facets of the NLRP3 inflammasome, with interventions aimed at directly inhibiting NLRP3 demonstrating the most promising efficacy and safety profiles. In this review, we provide a summary of direct inhibitors targeting NLRP3, elucidating their inhibitory mechanisms, clinical trial phases, and potential applications. Through this discussion, we aim to shed light on the implications of NLRP3 inhibition for the treatment of inflammatory diseases.