Evidence map›Paper›PMID 32367036›Full record

ArticleNature immunology2020

FDA-approved disulfiram inhibits pyroptosis by blocking gasdermin D pore formation.

Jun Jacob Hu, Xing Liu, Shiyu Xia, Zhibin Zhang, Ying Zhang, Jingxia Zhao, Jianbin Ruan, Xuemei Luo, Xiwen Lou, Yang Bai and 8 more

Registry-linked trialOpen access · greenAbstract read
In one paragraph

Article in Nature immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04485130 (DISulfiram for COvid-19), which is not on this map. Cited by 687 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
687citing papers in PubMed, 1 pooled it
46.8field-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.

NCT04485130 phase2terminatednot on this mapstarted 2021, after this paper: background citation

DISulfiram for COvid-19 (DISCO) Trial: A Phase 2 Double-Blind, Randomized Placebo-Controlled Trial of Disulfiram Compared to Standard Care in Patients With Symptomatic COVID-19

TypeinterventionalSponsorUniversity of California, San FranciscoRan2021 to 2022Enrolled11ConditionsCovid19ArmsDisulfiram, Placebo
3 · Its place in the literature

Who cites it

687 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,045 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. The gasdermin family: from pyroptosis mechanisms to therapeutic targets.Signal transduction and targeted therapy · 2026
    Review
  6. Disulfiram Attenuates Adenine-Induced Renal Fibrosis by Modulating Inflammatory and Immunometabolic Responses.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  7. Review
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
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  18. Article
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627 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 4 institutions in 2 countries.

Jun Jacob Hu *Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0001-7098-6272
Xing Liu *Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA. xingliu@ips.ac.cn.ORCID http://orcid.org/0000-0002-6277-3856
Shiyu XiaProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0001-9024-0689
Zhibin ZhangProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
Ying ZhangProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-1116-2182
Jingxia ZhaoProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
Jianbin RuanProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
Xuemei LuoBiomolecular Resource Facility, University of Texas Medical Branch, Galveston, TX, USA.
Xiwen LouThe Center for Microbes, Development and Health, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
Yang BaiThe Center for Microbes, Development and Health, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
Junhong WangThe Center for Microbes, Development and Health, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
L Robert HollingsworthProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-4130-3580
Venkat Giri MagupalliProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0003-4638-3062
Li ZhaoDepartment of Laboratory Medicine, The Stem Cell Program, Boston Children's Hospital, Boston, MA, USA.
Hongbo R LuoDepartment of Laboratory Medicine, The Stem Cell Program, Boston Children's Hospital, Boston, MA, USA.
Justin KimDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
Judy LiebermanProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA. judy.lieberman@childrens.harvard.edu.ORCID http://orcid.org/0000-0002-6200-4715
Hao WuProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA. wu@crystal.harvard.edu.ORCID http://orcid.org/0000-0002-7281-8579
Boston Children's Hospital · USChinese Academy of Sciences · CNHarvard University · USThe University of Texas Medical Branch at Galveston · US

Funding

Transcription regulation in hematopoiesisP01HL095489 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI LUO, HONGBO R · 2010 to 2020
$20.1M
Enhancing neutrophil function in neutropenia-related pneumoniaR01HL092020 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI LUO, HONGBO R · 2009 to 2022
$5.2M
SMOCs: Novel Signal Transduction Complexes as New Targets for Drug DiscoveryDP1HD087988 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI WU, HAO · 2015 to 2019
$4.4M
Elucidating the structural mechanism of pore formation by the (GSDM) Gasdermin familyR01AI139914 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI WU, HAO · 2018 to 2022
$2.6M
Regulation of neutrophil death by GSDMD in Candida albicans infectionR01AI145274 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI LUO, HONGBO R · 2019 to 2023
$2.2M
Regulation of IL-1β bioactivity by Cysteine S-glutathionylationR01AI142642 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI LUO, HONGBO R · 2019 to 2023
$2.2M
Granulysin, Granzymes and Perforin in Bacterial Immune DefenseR01AI123265 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI LIEBERMAN, JUDY · 2016 to 2020
$2.2M
Cell-based high-throughput chemical genetic screening for GSDMD inhibitorsR01AI141386 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI LUO, HONGBO R · 2019 to 2022
$1.8M
NHLBI NIH HHS P01 HL095489NHLBI NIH HHS R01 HL092020NIAID NIH HHS R01 AI123265NIAID NIH HHS R01 AI139914NIAID NIH HHS R01 AI141386NIAID NIH HHS R01 AI142642NIAID NIH HHS R01 AI145274NICHD NIH HHS DP1 HD087988
6 · The paper itself

Abstract

Cytosolic sensing of pathogens and damage by myeloid and barrier epithelial cells assembles large complexes called inflammasomes, which activate inflammatory caspases to process cytokines (IL-1β) and gasdermin D (GSDMD). Cleaved GSDMD forms membrane pores, leading to cytokine release and inflammatory cell death (pyroptosis). Inhibiting GSDMD is an attractive strategy to curb inflammation. Here we identify disulfiram, a drug for treating alcohol addiction, as an inhibitor of pore formation by GSDMD but not other members of the GSDM family. Disulfiram blocks pyroptosis and cytokine release in cells and lipopolysaccharide-induced septic death in mice. At nanomolar concentration, disulfiram covalently modifies human/mouse Cys191/Cys192 in GSDMD to block pore formation. Disulfiram still allows IL-1β and GSDMD processing, but abrogates pore formation, thereby preventing IL-1β release and pyroptosis. The role of disulfiram in inhibiting GSDMD provides new therapeutic indications for repurposing this safe drug to counteract inflammation, which contributes to many human diseases.

Indexed as

AnimalsCaspase 1Caspase InhibitorsCaspasesCaspases, InitiatorCell Line, TumorDisulfiramDrug Evaluation, PreclinicalDrug RepositioningFemaleGasderminsHEK293 CellsHigh-Throughput Screening AssaysHumansInterleukin-1betaIntracellular Signaling Peptides and ProteinsCasp4 protein, mouseCaspase 1caspase 11, humanCaspase InhibitorsCaspasesCaspases, InitiatorDisulfiramGasderminsGSDMD protein, humanGsdmd protein, mouseInterleukin-1betaIntracellular Signaling Peptides and ProteinsLipopolysaccharidesLiposomesPhosphate-Binding ProteinsRecombinant Proteins

Identifiers

PMID32367036
PMCPMC7316630
OpenAlexW3022981886

What OpenQuestion holds

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Registered trials

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.