Evidence map›Paper›PMID 41991983›Full record

ArticleCommunications biology2026

TH5487 specifically targets NLRP3 in FCAS patients resistant to MCC950.

Angela Lackner, Sofia I Picucci, Wenjin Jiang, Janset Onyuru, Melissa Campos, Julia E Cabral, Lemuel Leonidas, Alijah Macapagal, Hannah Lee, Valerie Henriquez and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Communications biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Angela LacknerLaboratory of Macromolecular Structure, Department of Molecular Biology & Biochemistry, Charlie Dunlop School of Biological Sciences, University of California, Irvine, CA, USA.
Sofia I PicucciLaboratory of Macromolecular Structure, Department of Molecular Biology & Biochemistry, Charlie Dunlop School of Biological Sciences, University of California, Irvine, CA, USA.ORCID http://orcid.org/0009-0004-2173-3497
Wenjin JiangLaboratory of Macromolecular Structure, Department of Molecular Biology & Biochemistry, Charlie Dunlop School of Biological Sciences, University of California, Irvine, CA, USA.
Janset OnyuruDivision of Pediatric Allergy, Immunology, and Rheumatology, Rady Children's Hospital of San Diego, University of California San Diego School of Medicine, San Diego, CA, USA.
Melissa CamposDepartment of Developmental and Cell Biology, Charlie Dunlop School of Biological Sciences, University of California, Irvine, CA, USA.
Julia E CabralLaboratory of Macromolecular Structure, Department of Molecular Biology & Biochemistry, Charlie Dunlop School of Biological Sciences, University of California, Irvine, CA, USA.ORCID http://orcid.org/0000-0001-6072-6362
Lemuel LeonidasLaboratory of Macromolecular Structure, Department of Molecular Biology & Biochemistry, Charlie Dunlop School of Biological Sciences, University of California, Irvine, CA, USA.
Alijah MacapagalLaboratory of Macromolecular Structure, Department of Molecular Biology & Biochemistry, Charlie Dunlop School of Biological Sciences, University of California, Irvine, CA, USA.
Hannah LeeLaboratory of Macromolecular Structure, Department of Molecular Biology & Biochemistry, Charlie Dunlop School of Biological Sciences, University of California, Irvine, CA, USA.
Valerie HenriquezLaboratory of Macromolecular Structure, Department of Molecular Biology & Biochemistry, Charlie Dunlop School of Biological Sciences, University of California, Irvine, CA, USA.
Karen WangLaboratory of Macromolecular Structure, Department of Molecular Biology & Biochemistry, Charlie Dunlop School of Biological Sciences, University of California, Irvine, CA, USA.
Huilin XuLaboratory of Macromolecular Structure, Department of Molecular Biology & Biochemistry, Charlie Dunlop School of Biological Sciences, University of California, Irvine, CA, USA.
Yanfei QiuLaboratory of Macromolecular Structure, Department of Molecular Biology & Biochemistry, Charlie Dunlop School of Biological Sciences, University of California, Irvine, CA, USA.
Lauren V AlbrechtDepartment of Developmental and Cell Biology, Charlie Dunlop School of Biological Sciences, University of California, Irvine, CA, USA.
Hal M HoffmanDivision of Pediatric Allergy, Immunology, and Rheumatology, Rady Children's Hospital of San Diego, University of California San Diego School of Medicine, San Diego, CA, USA.
Reginald McNultyLaboratory of Macromolecular Structure, Department of Molecular Biology & Biochemistry, Charlie Dunlop School of Biological Sciences, University of California, Irvine, CA, USA. rmcnulty@uci.edu.ORCID http://orcid.org/0000-0003-2101-1377

Funding

Macromolecular assemblies of transcription factors initiated by pathogen infectionK22AI139444 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI MCNULTY, REGINALD · 2019 to 2021
$297k
U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) K22AI139444
6 · The paper itself

Abstract

Aberrant activation of the NLRP3 inflammasome contributes to a wide range of chronic inflammatory disorders. Here, we investigate small-molecule inhibitors originally developed to target the DNA repair enzyme hOGG1 and demonstrate their ability to inhibit NLRP3 activation in human cells. These compounds, including TH5487 (IC50 1.62 µM in human PBMCs), reduce IL-1β secretion while increasing type I interferon responses. Cryo-EM reveals direct association between NLRP3 and mitochondrial DNA, while structural modeling predicts interaction with oxDNA. Notably, inhibitors of the DNA repair glycosylase hOGG1 remain effective in L353P mutant PBMCs from FCAS patients and L351P in mice, at doses where the canonical NLRP3 inhibitor MCC950 is ineffective. Our findings uncover an additional druggable mechanism for inflammasome regulation via interference with oxidized DNA sensing, offering innovative therapeutic opportunities for autoinflammatory disease.

Indexed as

NLR Family, Pyrin Domain-Containing 3 ProteinAnimalsDNA GlycosylasesDNA, MitochondrialFuransHumansInflammasomesMiceDNA GlycosylasesDNA, MitochondrialFuransInflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinNLRP3 protein, humanoxoguanine glycosylase 1, human

Identifiers

PMID41991983
PMCPMC13086942

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Registered trials

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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.