Evidence map›Paper›PMID 25686105›Full record

ArticleNature medicine2015

A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases.

Rebecca C Coll, Avril A B Robertson, Jae Jin Chae, Sarah C Higgins, Raúl Muñoz-Planillo, Marco C Inserra, Irina Vetter, Lara S Dungan, Brian G Monks, Andrea Stutz and 12 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,570 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1,570citing papers in PubMed, 2 pooled it
76.5field-weighted citation impact, top 1% 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

1,570 citing papers in PubMed, 2 syntheses or guidelines pooled it, 2,700 citations in OpenAlex.

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1,510 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors at 6 institutions in 5 countries.

Rebecca C Coll1] School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland. [2] Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
Avril A B RobertsonInstitute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
Jae Jin ChaeInflammatory Disease Section, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
Sarah C HigginsSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Raúl Muñoz-PlanilloDepartment of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Marco C Inserra1] Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia. [2] School of Pharmacy, University of Queensland, Brisbane, Australia.
Irina Vetter1] Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia. [2] School of Pharmacy, University of Queensland, Brisbane, Australia.
Lara S DunganSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Brian G MonksInstitute of Innate Immunity, University Hospital, University of Bonn, Bonn, Germany.
Andrea StutzInstitute of Innate Immunity, University Hospital, University of Bonn, Bonn, Germany.
Daniel E CrokerInstitute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
Mark S ButlerInstitute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
Moritz HaneklausSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Caroline E SuttonSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Gabriel NúñezDepartment of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Eicke Latz1] Institute of Innate Immunity, University Hospital, University of Bonn, Bonn, Germany. [2] Department of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA. [3] German Center for Neurodegenerative Diseases, Bonn, Germany.
Daniel L KastnerInflammatory Disease Section, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
Kingston H G MillsSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Seth L MastersThe Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.ORCID 000000034763576X
Kate SchroderInstitute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
Matthew A CooperInstitute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
Luke A J O'NeillSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
The University of Queensland · AUTrinity College Dublin · IEUniversity of Bonn · DENational Institutes of Health · USUniversity of Michigan · USWalter and Eliza Hall Institute of Medical Research · AU

Funding

Genetics, Pathophysiology, and Treatment of Dominant Autoinflammatory DiseasesZIAHG200373 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI KASTNER, DANIEL · 2011 to 2024
$21.0M
Role of Immunity and the Microbiota in Enteropathogenic E. coli EradicationR01DK095782 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI NUNEZ, GABRIEL · 2013 to 2022
$3.6M
The Role of Inflammasomes in Mucosal Immunity to Intestinal Bacterial PathogensR01DK091191 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI NUNEZ, GABRIEL · 2010 to 2019
$3.1M
HDL prevention of cholesterol crystal inflammation in HIV diseaseR01HL112661 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI FITZGERALD, MICHAEL LEO, LATZ, EICKE · 2012 to 2016
$3.1M
Intramural NIH HHSNHLBI NIH HHS R01 HL112661NIDDK NIH HHS DK091191NIDDK NIH HHS DK095782NIDDK NIH HHS R01 DK091191NIDDK NIH HHS R01 DK095782
6 · The paper itself

Abstract

The NOD-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome is a component of the inflammatory process, and its aberrant activation is pathogenic in inherited disorders such as cryopyrin-associated periodic syndrome (CAPS) and complex diseases such as multiple sclerosis, type 2 diabetes, Alzheimer's disease and atherosclerosis. We describe the development of MCC950, a potent, selective, small-molecule inhibitor of NLRP3. MCC950 blocked canonical and noncanonical NLRP3 activation at nanomolar concentrations. MCC950 specifically inhibited activation of NLRP3 but not the AIM2, NLRC4 or NLRP1 inflammasomes. MCC950 reduced interleukin-1β (IL-1β) production in vivo and attenuated the severity of experimental autoimmune encephalomyelitis (EAE), a disease model of multiple sclerosis. Furthermore, MCC950 treatment rescued neonatal lethality in a mouse model of CAPS and was active in ex vivo samples from individuals with Muckle-Wells syndrome. MCC950 is thus a potential therapeutic for NLRP3-associated syndromes, including autoinflammatory and autoimmune diseases, and a tool for further study of the NLRP3 inflammasome in human health and disease.

Indexed as

Multiple SclerosisAnimalsCarrier ProteinsCryopyrin-Associated Periodic SyndromesDisease Models, AnimalEncephalomyelitis, Autoimmune, ExperimentalFuransHeterocyclic Compounds, 4 or More RingsHumansIndenesInflammasomesInflammationInterleukin-1betaMiceNLR Family, Pyrin Domain-Containing 3 ProteinSulfonamidesCarrier ProteinsFuransHeterocyclic Compounds, 4 or More RingsIL1B protein, mouseIndenesInflammasomesInterleukin-1betaN-(1,2,3,5,6,7-hexahydro-S-indacen-4-ylcarbamoyl)-4-(2-hydroxy-2-propanyl)-2-furansulfonamideNLR Family, Pyrin Domain-Containing 3 ProteinNLRP3 protein, humanNlrp3 protein, mouseSulfonamidesSulfones

Identifiers

PMID25686105
PMCPMC4392179
OpenAlexW2140637559

What OpenQuestion holds

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Registered trials

None linked

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.