ArticleThe Journal of experimental medicine2025
Discovery of potent and selective inhibitors of human NLRP3 with a novel mechanism of action.
Article in The Journal of experimental medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed.
- NLRP3 Regulation in Neonatal Hypoxic-Ischemic Encephalopathy-Focus on Microglial Activation.International journal of molecular sciences · 2026Article
- Induced pluripotent stem cell-derived macrophages enable broad modeling of human inflammasome signaling.Cell reports methods · 2026Article
- Reactive Oxygen and Nitrogen Species on Monocyte and Macrophage Biology.Antioxidants (Basel, Switzerland) · 2026Review
- Localized inflammasome inhibition mitigates foreign body response to subcutaneous long-acting antiretroviral therapy for HIV.Journal of controlled release : official journal of the Controlled Release Society · 2026Article
- Top 100 most-cited articles on NLRP3 (2000-2024): a retrospective analysis.Frontiers in immunology · 2026Article
- Operationalizing Chronic Inflammation: An Endotype-to-Care Framework for Precision and Equity.Clinics and practice · 2025Review
- Environmental Stressors and Neuroinflammation: Linking Climate Change to Alzheimer's Disease.Current issues in molecular biology · 2025Review
Corrections and comments
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Authors and funding
35 authors.
Funding
Abstract
The NLRP3 inflammasome is an intracellular protein complex that causes inflammation via the release of IL-1β and pyroptosis. NLRP3 activation is associated with many age-related inflammatory diseases, and NLRP3 inhibition is a promising therapeutic strategy. We previously performed a DNA-encoded library screen to identify novel NLRP3-binding molecules. Herein we describe the characterization of BAL-0028 as a potent and specific inhibitor of NLRP3 signaling. Notably, BAL-0028 is a poor inhibitor of mouse NLRP3 but inhibits human and primate NLRP3 with nanomolar potency. Using cellular and biochemical analyses, we demonstrate that BAL-0028 binds to the NLRP3 NACHT domain at a site that is distinct from the MCC950-binding pocket. Using humanized NLRP3 mice, we show that a derivative of BAL-0028, BAL-0598, inhibits NLRP3 activation in vivo in a peritonitis model. Finally, we demonstrate that both BAL-0028 and BAL-0598 inhibit select hyperactive NLRP3 mutations associated with autoinflammatory diseases more potently than MCC950. BAL-0028 and BAL-0598 thus represent a new modality for NLRP3 inhibition in inflammatory diseases.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.