Background: Inflammation is the body’s immune system’s fast coordinating response to
irritants caused by pathogens, external injuries, and chemical or radiation effects. The nucleotidebinding
oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome
is a critical component of the innate immune system. The dysfunction of NLRP3 inflammasome
contributes to various pathogeneses of complex diseases, such as uncontrolled infection, autoimmune
diseases, neurodegenerative diseases, and metabolic disorders. This review describes recent
progress on the discovery of NLRP3 inflammasome inhibitors and their therapeutic potential.
Methods: Based on the mechanism of NLRP3 activation, several types of NLRP3 inhibitors are described
and summarized according to their origins, structures, bioactivity, and mechanism of action.
Structure-Activity Relationship (SAR) is also listed for different scaffolds, as well as effective pharmacophore.
Results: Over one-hundred papers were included in the review. The development of NLRP3 inhibitors
has been described from the earliest glyburide in 2001 to the latest progress in 2019. Several series of
inhibitors have been categorized, such as JC-series based on glyburide and BC-series based on 2APB.
Many other small molecules such as NLRP3 inhibitors are also listed. SAR, application in related therapeutic
models, and five different action mechanisms are described.
Conclusion: The findings of this review confirmed the importance of developing NLRP3 inflammasome
inhibitors. Various NLRP3 inhibitors have been discovered as effective therapeutic treatments
for multiple diseases, such as type II diabetes, experimental autoimmune encephalomyelitis, stressrelated
mood disorders, etc. The development of a full range of NLRP3 inflammasome inhibitors is still
at its foundational phase. We are looking forward to the identification of inhibitory agents that provide
the most potent therapeutic strategies and efficiently treat NLRP3 inflammasome-related inflammatory