dapansutrile (OLT1177)

This broader perspective illustrates the wider impact of inflammasome-mediated pathophysiology in chemotherapy-induced cardiac failure and goes beyond traditional doxorubicin-centered treatments. The review also provides an overview of the therapeutic landscape of selective NLRP3 inhibition, including natural modulators such as oridonin, curcumin, resveratrol, honokiol, and flavonoids, as well as synthetic inhibitors such as MCC950, CY-09, OLT1177 (dapansutrile), and tranilast...Despite encouraging preclinical findings, translational challenges remain, including long-term safety assessment. Modulation of NLRP3 inflammasome activation has emerged as a potential intervention to limit chemotherapy-induced cardiac injury and dysfunction in cardio-oncology.

P2, N=36, Recruiting, Cambridge University Hospitals NHS Foundation Trust | Trial completion date: Feb 2028 --> Jun 2028 | Trial primary completion date: Aug 2027 --> May 2027

P2/3, N=300, Recruiting, Olatec Therapeutics LLC | Trial completion date: Aug 2026 --> Jan 2027 | Trial primary completion date: Jul 2026 --> Dec 2026

Therapeutic interventions with NLRP3 inflammasome inhibitors (MCC950 and dapansutrile) and a macrophage-depleting agent (clodronate liposomes) were evaluated by micro-computed tomography (CT), histopathology, and serum inflammatory cytokine assays. The findings revealed: (I) significant upregulation of NLRP3 inflammasome pathway-related genes and downstream factors (IL-1β, IL-18) in CIP mouse lungs, alongside increased macrophage infiltration; (II) pneumonitis injury was markedly alleviated and serum inflammatory cytokine levels were reduced by both NLRP3 inflammasome inhibition and macrophage depletion; (III) dapansutrile downregulated NLRP3 expression via inhibition of the NF-κB pathway; (IV) enriched macrophage subpopulations (Mac-IL1B) expressing high levels of NLRP3 were identified in CIP patients. This study provides the first evidence that NLRP3 inflammasome activation constitutes a key upstream mechanism in CIP pathogenesis, offering novel therapeutic strategies for targeted intervention.

P2, N=36, Recruiting, Cambridge University Hospitals NHS Foundation Trust | Not yet recruiting --> Recruiting | Initiation date: Nov 2025 --> Feb 2026

Furthermore, dapansutrile exhibits synergistic effects when combined with agents such as lonafarnib or immune 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.

P2/3, N=300, Recruiting, Olatec Therapeutics LLC | Trial completion date: Dec 2025 --> Aug 2026 | Trial primary completion date: Nov 2025 --> Jul 2026

P2, N=36, Not yet recruiting, Cambridge University Hospitals NHS Foundation Trust

P1, N=60, Not yet recruiting, University of Virginia | Trial completion date: Oct 2028 --> Jan 2029 | Trial primary completion date: Dec 2027 --> Dec 2028

P2/3, N=300, Recruiting, Olatec Therapeutics LLC | Trial completion date: Oct 2025 --> Dec 2025

P2/3, N=300, Recruiting, Olatec Therapeutics LLC | Trial completion date: Dec 2025 --> Oct 2025 | Trial primary completion date: Nov 2025 --> Sep 2025

P2/3, N=300, Recruiting, Olatec Therapeutics LLC | Trial completion date: Oct 2024 --> Dec 2025 | Trial primary completion date: Oct 2024 --> Nov 2025