Strategies for Targeting the NLRP3 Inflammasome in the Clinical and Preclinical Space

Inhibiting the NLRP3 inflammasome mediates inflammation in an extensive number of preclinical models. As excitement in this field has grown, several companies have recently initiated testing of direct NLRP3 inhibitors in the clinic. At the same time, the NLRP3 inflammasome is part of a larger pro-inflammatory pathway, whose modulation is also being explored. Multiple targets in this pathway are already impinged upon by molecules that have been through clinical trials. These data, informed by the growing mechanistic understanding of the NLRP3 inflammasome in the preclinical space, provide a rich backdrop to assess the current state of the field. Here we explore attempts to inhibit the NLRP3 inflammasome in light of clinical and preclinical data around efficacy and safety.