REVIEW article
Front. Pharmacol.
Sec. Inflammation Pharmacology
Dapansutrile in Multidisciplinary Therapeutic Applications: mechanisms and clinical perspectives
Provisionally accepted
- Sichuan University West China School of Stomatology, Chengdu, China
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Dapansutrile, an orally active and selective NLRP3 inflammasome inhibitor, exerts its effects by directly binding to the NLRP3 NACHT domain. This action disrupts inflammasome assembly and caspase-1 activation, thereby inhibiting the maturation and release of the pro-inflammatory cytokines IL-1β and IL-18. Beyond this core inhibition, dapansutrile modulates immune cell chemotaxis and inhibits pyroptosis. Preclinical and clinical studies demonstrate its efficacy in mitigating pathology in diverse conditions, including gouty arthritis, cardiovascular diseases, neurodegenerative disorders, inflammatory bowel disease, and periodontitis. A favorable safety profile distinguishes it from other NLRP3 inhibitors like MCC950, with no significant hepatotoxicity reported in trials. Furthermore, dapansutrile exhibits synergistic effects when combined with agents such as lonafarnib or immune This is a provisional file, not the final typeset article checkpoint inhibitors, enhancing anti-inflammatory and anti-tumor responses. This review consolidates evidence on dapansutrile's molecular mechanisms, therapeutic applications, and biosafety, highlighting its potential as a novel, well-tolerated, and versatile anti-inflammatory agent. Future research should focus on optimizing its delivery, particularly to the central nervous system, and leveraging artificial intelligence to predict effective drug combinations.
Keywords: Dapansutrile1, anti-inflammatory2, NLRP3 inflammasome3, combination drugs4, OLT11755
Received: 23 Oct 2025; Accepted: 17 Nov 2025.
Copyright: © 2025 Bai, Wang and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yingying Wu, yingyingwu@scu.edu.cn
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