A Narrative Review of the Pharmacological Potential of Dapansutrile, a Selective NLRP3 Inflammasome Inhibitor.

OLT1177™ (Dapansutrile) is a newly developed drug that specifically inhibits the NLRP3 inflammasome and is safe in humans. Initially formulated as a topical treatment for degenerative arthritis, it has since been developed into an oral form. Both topical gel and oral capsules have demonstrated that OLT1177 is safe and well-tolerated in humans, with a satisfactory safety profile and efficacy in reducing target joint pain. Inflammasomes are cytoplasmic proteins that activate caspase-1 in response to microbial invasion and damage signals. The NLRP3 inflammasome is one of the NOD-like receptor family members and is widely studied and activated by various stimuli. NLRP3 inflammasome activation is regulated through a two-step process, with priming at transcriptional and posttranslational levels and assembly by multiple pathways. The NLRP3 inflammasome, which activates inflammation-related diseases, is primarily activated through K+ efflux, mitochondrial dysfunction, and lysosomal rupture. However, its regulation in humans remains unclear. NLRP3 inflammasome composition, downstream pathways, and inhibitor development offer the potential for treating inflammation-related diseases. Several inhibitors have emerged and are currently in clinical trials, with over 10 having completed trials and recruiting participants.