Evidence map›Paper›PMID 37598239›Full record

ArticleScientific reports2023

JT002, a small molecule inhibitor of the NLRP3 inflammasome for the treatment of autoinflammatory disorders.

Geza Ambrus-Aikelin, Katsuyuki Takeda, Anthony Joetham, Milos Lazic, Davide Povero, Angelina M Santini, Rama Pranadinata, Casey D Johnson, Matthew D McGeough, Federico C Beasley and 9 more

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2023. 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 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.8field-weighted citation impact, top 9% of its field
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

17 citing papers in PubMed, 18 citations in OpenAlex.

  1. Review
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  4. Targeting macrophages in liver fibrosis.Frontiers in immunology · 2026
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  8. Candida albicans: the current status regarding vaginal infections.Applied microbiology and biotechnology · 2025
    Review
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  13. A guide to cell death pathways.Nature reviews. Molecular cell biology · 2024
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 3 institutions in 1 country.

Geza Ambrus-AikelinJecure Therapeutics, San Diego, CA, USA.
Katsuyuki TakedaDepartment of Pediatrics, National Jewish Health, Denver, CO, USA.
Anthony JoethamDepartment of Pediatrics, National Jewish Health, Denver, CO, USA.
Milos LazicJecure Therapeutics, San Diego, CA, USA.
Davide PoveroJecure Therapeutics, San Diego, CA, USA. povero.davide@mayo.edu.
Angelina M SantiniJecure Therapeutics, San Diego, CA, USA.
Rama PranadinataJecure Therapeutics, San Diego, CA, USA.
Casey D JohnsonDepartment of Pediatrics, University of California San Diego, La Jolla, CA, USA.
Matthew D McGeoughDepartment of Pediatrics, University of California San Diego, La Jolla, CA, USA.
Federico C BeasleyJecure Therapeutics, San Diego, CA, USA.
Ryan StansfieldJecure Therapeutics, San Diego, CA, USA.
Christopher McBrideJecure Therapeutics, San Diego, CA, USA.
Lynnie TrzossJecure Therapeutics, San Diego, CA, USA.
Hal M HoffmanDepartment of Pediatrics, University of California San Diego, La Jolla, CA, USA.
Ariel E FeldsteinDepartment of Pediatrics, University of California San Diego, La Jolla, CA, USA.
Jeffrey A StaffordJecure Therapeutics, San Diego, CA, USA.
James M VealJecure Therapeutics, San Diego, CA, USA.
Gretchen BainJecure Therapeutics, San Diego, CA, USA.
Erwin W GelfandDepartment of Pediatrics, National Jewish Health, Denver, CO, USA.
University of California, San Diego · USUniversity of Colorado Denver · USNational Jewish Health · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The NLRP3 inflammasome is an intracellular, multiprotein complex that promotes the auto-catalytic activation of caspase-1 and the subsequent maturation and secretion of the pro-inflammatory cytokines, IL-1β and IL-18. Persistent activation of the NLRP3 inflammasome has been implicated in the pathophysiology of a number of inflammatory and autoimmune diseases, including neuroinflammation, cardiovascular disease, non-alcoholic steatohepatitis, lupus nephritis and severe asthma. Here we describe the preclinical profile of JT002, a novel small molecule inhibitor of the NLRP3 inflammasome. JT002 potently reduced NLRP3-dependent proinflammatory cytokine production across a number of cellular assays and prevented pyroptosis, an inflammatory form of cell death triggered by active caspase-1. JT002 demonstrated in vivo target engagement at therapeutically relevant concentrations when orally dosed in mice and prevented body weight loss and improved inflammatory and fibrotic endpoints in a model of Muckle-Wells syndrome (MWS). In two distinct models of neutrophilic airway inflammation, JT002 treatment significantly reduced airway hyperresponsiveness and airway neutrophilia. These results provide a rationale for the therapeutic targeting of the NLRP3 inflammasome in severe asthma and point to the use of JT002 in a variety of inflammatory disorders.

Indexed as

Cardiovascular DiseasesLupus NephritisAnimalsCaspase 1InflammasomesMiceNLR Family, Pyrin Domain-Containing 3 ProteinCaspase 1InflammasomesNLR Family, Pyrin Domain-Containing 3 Protein

Identifiers

PMID37598239
PMCPMC10439952
OpenAlexW4386001332

What OpenQuestion holds

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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.