ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
UK5099 Inhibits the NLRP3 Inflammasome Independently of its Long-Established Target Mitochondrial Pyruvate Carrier.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Ciclopirox Olamine Inhibits the NLRP3 Inflammasome to Alleviate Inflammatory Diseases.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Metabolic pattern changes of macrophages during cancer development and progression.Journal of translational medicine · 2026Review
- Breakthroughs of ultrasound-targeted microbubble destruction in treating myocardial ischemia-reperfusion injury: from angiogenesis regulation to precise inflammation suppression.Drug delivery · 2025Review
- Ace2 safeguards embryonic hematopoietic stem and progenitor cell production by restraining Nlrp3-mediated pyroptosis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- In Silico Identification of the NLRP3 Inhibitors from Traditional Chinese Medicine.International journal of molecular sciences · 2025Article
- Cuproptosis and Cardiovascular Diseases: Mechanisms, Pathophysiology, and Therapeutic Strategies-A Narrative Review.Reviews in cardiovascular medicine · 2025Review
- Pinosylvin Inhibits Inflammatory and Osteoclastogenesis via NLRP3 Inflammasome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Folium Hibisci Mutabilis extract suppresses M1 macrophage polarization through mitochondrial function enhancement in murine acute gouty arthritis.Chinese medicine · 2025Article
- Activation and evasion of inflammasomes during viral and microbial infection.Cellular and molecular life sciences : CMLS · 2025Review
- Pathogenesis and therapeutic applications of microglia receptors in Alzheimer's disease.Frontiers in immunology · 2025Review
- Pyroptosis in health and disease: mechanisms, regulation and clinical perspective.Signal transduction and targeted therapy · 2024Review
- UK5099 Inhibits the NLRP3 Inflammasome Independently of its Long-Established Target Mitochondrial Pyruvate Carrier.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
Targeting NLRP3 inflammasome has been recognized as a promising therapeutic strategy for the treatment of numerous common diseases. UK5099, a long-established inhibitor of mitochondrial pyruvate carrier (MPC), is previously found to inhibit macrophage inflammatory responses independent of MPC expression. However, the mechanisms by which UK5099 inhibit inflammatory responses remain unclear. Here, it is shown that UK5099 is a potent inhibitor of the NLRP3 inflammasome in both mouse and human primary macrophages. UK5099 selectively suppresses the activation of the NLRP3 but not the NLRC4 or AIM2 inflammasomes. Of note, UK5099 retains activities on NLRP3 in macrophages devoid of MPC expression, indicating this inhibitory effect is MPC-independent. Mechanistically, UK5099 abrogates mitochondria-NLRP3 interaction and in turn inhibits the assembly of the NLRP3 inflammasome. Further, a single dose of UK5099 persistently reduces IL-1β production in an endotoxemia mouse model. Importantly, structure modification reveals that the inhibitory activities of UK5099 on NLRP3 are unrelated to the existence of the activated double bond within the UK5099 molecule. Thus, this study uncovers a previously unknown molecular target for UK5099, which not only offers a new candidate for the treatment of NLRP3-driven diseases but also confounds its use as an MPC inhibitor in immunometabolism studies.
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