Evidence map›Paper›PMID 25826675›Full record

ArticleMolecular medicine (Cambridge, Mass.)2015

Macrophage migration inhibitory factor (MIF) enzymatic activity and lung cancer.

Leona Mawhinney, Michelle E Armstrong, Ciaran O' Reilly, Richard Bucala, Lin Leng, Gunter Fingerle-Rowson, Darren Fayne, Michael P Keane, Aisling Tynan, Lewena Maher and 4 more

Open access · goldAbstract read
In one paragraph

Article in Molecular medicine (Cambridge, Mass.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
1.9field-weighted citation impact, top 15% 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

34 citing papers in PubMed, 66 citations in OpenAlex.

  1. MIF Tautomerase Inhibition Protects Neurons From Immune-Mediated Cell Death.Neurology(R) neuroimmunology & neuroinflammation · 2026
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  14. RecombinantJournal for immunotherapy of cancer · 2021
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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

14 authors at 5 institutions in 4 countries.

Leona MawhinneyConway Institute for Biomolecular and Biomedical Research, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
Michelle E ArmstrongConway Institute for Biomolecular and Biomedical Research, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
Ciaran O' ReillyMolecular Design Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Richard BucalaDepartment of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.
Lin LengDepartment of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.
Gunter Fingerle-RowsonDepartment of Internal Medicine 1, University Hospital Cologne, Centre for Integrated Oncology Köln-Bonn, Cologne, Germany.
Darren FayneMolecular Design Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Michael P KeaneConway Institute for Biomolecular and Biomedical Research, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
Aisling TynanConway Institute for Biomolecular and Biomedical Research, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
Lewena MaherConway Institute for Biomolecular and Biomedical Research, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
Gordon CookeConway Institute for Biomolecular and Biomedical Research, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
David LloydDivision of Health Sciences, University of South Australia, Adelaide, Australia.
Helen ConroyConway Institute for Biomolecular and Biomedical Research, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
Seamas C DonnellyConway Institute for Biomolecular and Biomedical Research, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
University College Dublin · IETrinity College Dublin · IEYale University · USUniversity Hospital Cologne · DEUniversity of South Australia · AU

Funding

MIF AND THE HOST RESPONSE TO INFECTIONR01AI042310 · NIAID · YALE UNIVERSITY · PI BUCALA, RICHARD J · 1998 to 2013
$4.3M
MIF and Host Response to InfectionR56AI042310 · NIAID · YALE UNIVERSITY · PI BUCALA, RICHARD J · 2014 to 2014
$426k
NIAID NIH HHS AI042310NIAID NIH HHS R01 AI042310NIAID NIH HHS R56 AI042310
6 · The paper itself

Abstract

The cytokine macrophage migration inhibitory factor (MIF) possesses unique tautomerase enzymatic activity, which contributes to the biological functional activity of MIF. In this study, we investigated the effects of blocking the hydrophobic active site of the tautomerase activity of MIF in the pathogenesis of lung cancer. To address this, we initially established a Lewis lung carcinoma (LLC) murine model in Mif-KO and wild-type (WT) mice and compared tumor growth in a knock-in mouse model expressing a mutant MIF lacking enzymatic activity (Mif (P1G)). Primary tumor growth was significantly attenuated in both Mif-KO and Mif (P1G) mice compared with WT mice. We subsequently undertook a structure-based, virtual screen to identify putative small molecular weight inhibitors specific for the tautomerase enzymatic active site of MIF. From primary and secondary screens, the inhibitor SCD-19 was identified, which significantly attenuated the tautomerase enzymatic activity of MIF in vitro and in biological functional screens. In the LLC murine model, SCD-19, given intraperitoneally at the time of tumor inoculation, was found to significantly reduce primary tumor volume by 90% (p < 0.001) compared with the control treatment. To better replicate the human disease scenario, SCD-19 was given when the tumor was palpable (at d 7 after tumor inoculation) and, again, treatment was found to significantly reduce tumor volume by 81% (p < 0.001) compared with the control treatment. In this report, we identify a novel inhibitor that blocks the hydrophobic pocket of MIF, which houses its specific tautomerase enzymatic activity, and demonstrate that targeting this unique active site significantly attenuates lung cancer growth in in vitro and in vivo systems.

Indexed as

AnimalsAntineoplastic AgentsCarcinoma, Lewis LungCell LineDinoprostoneFemaleIntramolecular OxidoreductasesIsocoumarinsLipopolysaccharidesLungLung NeoplasmsMacrophage Migration-Inhibitory FactorsMice, Inbred C57BLMice, KnockoutTumor BurdenTumor Necrosis Factor-alpha3-(2'-methylphenyl)isocoumarinAntineoplastic AgentsDinoprostoneIntramolecular OxidoreductasesIsocoumarinsLipopolysaccharidesMacrophage Migration-Inhibitory FactorsMif protein, mouseTumor Necrosis Factor-alpha

Identifiers

PMID25826675
PMCPMC4398672
OpenAlexW221215209

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.