ArticleScientific reports2021
A phenotypic high-content, high-throughput screen identifies inhibitors of NLRP3 inflammasome activation.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Nanoadjuvant-integrated organic biomaterials for immune engineering: Mechanisms, design strategies, and translational applications.Materials today. Bio · 2026Review
- The NLRP3 Inflammasome: Mechanisms of Activation, Regulation, and Therapeutic Opportunities.MedComm · 2026Review
- The Heterocycle Isostere Explorer: A Computational Tool for the Discovery of Novel Aromatic Heterocyclic Isosteres.Journal of medicinal chemistry · 2026Article
- Neuroinflammatory mechanisms and pharmacological advances in autism spectrum disorder: from inflammatory pathways to targeted interventions.Frontiers in immunology · 2026Review
- A comprehensive update on the application of high-throughput fluorescence imaging for novel drug discovery.Expert opinion on drug discovery · 2025Review
- Molecular insights into NLRP3 inflammasome and miRNA modulation in oral cancer.Frontiers in pharmacology · 2025Review
- A combined AI and cell biology approach surfaces targets and mechanistically distinct Inflammasome inhibitors.iScience · 2024Article
- Inhibition of the JAK/STAT Pathway With Baricitinib Reduces the Multiple Organ Dysfunction Caused by Hemorrhagic Shock in Rats.Annals of surgery · 2023Article
- Novel Activity of ODZ10117, a STAT3 Inhibitor, for Regulation of NLRP3 Inflammasome Activation.International journal of molecular sciences · 2023Article
- High-throughput phenotypic screen identifies a new family of potent anti-amoebic compounds.PloS one · 2023Article
- Review
- Potential of nobiletin against Alzheimer's disease through inhibiting neuroinflammation.Metabolic brain disease · 2022Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inhibition of the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome has recently emerged as a promising therapeutic target for several inflammatory diseases. After priming and activation by inflammation triggers, NLRP3 forms a complex with apoptosis-associated speck-like protein containing a CARD domain (ASC) followed by formation of the active inflammasome. Identification of inhibitors of NLRP3 activation requires a well-validated primary high-throughput assay followed by the deployment of a screening cascade of assays enabling studies of structure-activity relationship, compound selectivity and efficacy in disease models. We optimized a NLRP3-dependent fluorescent tagged ASC speck formation assay in murine immortalized bone marrow-derived macrophages and utilized it to screen a compound library of 81,000 small molecules. Our high-content screening assay yielded robust assay metrics and identified a number of inhibitors of NLRP3-dependent ASC speck formation, including compounds targeting HSP90, JAK and IKK-β. Additional assays to investigate inflammasome priming or activation, NLRP3 downstream effectors such as caspase-1, IL-1β and pyroptosis form the basis of a screening cascade to identify NLRP3 inflammasome inhibitors in drug discovery programs.
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