Evidence map›Paper›PMID 39297418›Full record

ArticleACS chemical neuroscience2024

Functional Characterization of an Arylsulfonamide-Based Small-Molecule Inhibitor of the NLRP3 Inflammasome.

Savannah Biby, Prasenjit Mondal, Yiming Xu, Ashley Gomm, Baljit Kaur, Jannatun N Namme, Changning Wang, Rudolph E Tanzi, Shijun Zhang, Can Zhang

Abstract read
In one paragraph

Article in ACS chemical neuroscience, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Savannah BibyDepartment of Medicinal Chemistry, Virginia Commonwealth University, Richmond, Virginia 23298, United States.ORCID 0009-0004-4063-9682
Prasenjit MondalGenetics and Aging Research Unit, McCance Center for Brain Health, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, United States.
Yiming XuDepartment of Medicinal Chemistry, Virginia Commonwealth University, Richmond, Virginia 23298, United States.
Ashley GommGenetics and Aging Research Unit, McCance Center for Brain Health, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, United States.
Baljit KaurDepartment of Medicinal Chemistry, Virginia Commonwealth University, Richmond, Virginia 23298, United States.ORCID 0000-0002-0461-6692
Jannatun N NammeDepartment of Medicinal Chemistry, Virginia Commonwealth University, Richmond, Virginia 23298, United States.
Changning WangAthinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, United States.ORCID 0000-0002-2076-4193
Rudolph E TanziGenetics and Aging Research Unit, McCance Center for Brain Health, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, United States.
Shijun ZhangDepartment of Medicinal Chemistry, Virginia Commonwealth University, Richmond, Virginia 23298, United States.ORCID 0000-0001-9732-5925
Can ZhangGenetics and Aging Research Unit, McCance Center for Brain Health, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, United States.ORCID 0000-0002-4340-5118

Funding

Development of novel NLRP3 inflammasome inhibitors for intervening in Alzheimer's diseaseU01AG076481 · NIA · VIRGINIA COMMONWEALTH UNIVERSITY · PI Shijun Zhang · 2022 to 2026
$7.5M
Probing neuroinflammation in Alzheimer's disease with NLRP3 PET radiotracersRF1AG076912 · NIA · VIRGINIA COMMONWEALTH UNIVERSITY · PI ZHANG, SHIJUN · 2023 to 2023
$1.9M
NIA NIH HHS RF1 AG076912NIA NIH HHS U01 AG076481
6 · The paper itself

Abstract

Considerable evidence indicates that the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome plays key roles in human pathophysiology, suggesting it as a potential drug target. Currently, studies have yet to develop compounds that are promising therapeutics in the clinic by targeting the NLRP3 inflammasome. Herein, we aim to further biologically characterize a previously identified small-molecule inhibitor of the NLRP3 inflammasome from our group, YM-I-26, to confirm its functional activities. We showed that YM-I-26 is highly selective toward the NLRP3 inflammasome and binds to NLRP3 directly. A systemic analysis revealed YM-I-26 with inflammation-related and immunomodulatory activities by the Eurofins BioMAP Diversity PLUS panel. In addition, studies using the mouse microglia BV2 cell model demonstrated that YM-I-26 is not cytotoxic, improved the phagocytotic functions of BV2 cells toward beta-amyloid, and suppressed the production of cytokines of IL-1β and IL-10 upon the activation of the NLRP3 inflammasome. Collectively, our studies support the functional activities of YM-I-26 as a NLRP3 inhibitor in physiologically relevant cell models, and warrant future studies of YM-I-26 and its analogs to advance the drug development as potential therapeutics.

Indexed as

InflammasomesMicrogliaNLR Family, Pyrin Domain-Containing 3 ProteinSulfonamidesAnimalsCell LineHumansMiceInflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseSulfonamidesbinding interactioninhibitormicroglianeuroinflammationNOD-like receptor family pyrin domain containing 3 (NLRP3)phagocytosis

Identifiers

PMID39297418
PMCPMC11450741

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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.