ArticleMolecular medicine (Cambridge, Mass.)2024
Iguratimod, an allosteric inhibitor of macrophage migration inhibitory factor (MIF), prevents mortality and oxidative stress in a murine model of acetaminophen overdose.
Article in Molecular medicine (Cambridge, Mass.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 5 citations in OpenAlex.
- Generation of MIF Peptides via Solid Phase Peptide Synthesis.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Assessing the Tautomerase Activity of MIF Using L-Dopachrome.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Macrophage migration inhibitory factor: Exploring physiological roles and comparing health benefits against oncogenic and autoimmune risks (Review).International journal of molecular medicine · 2025Review
- Inhibition of MIF with an Allosteric Inhibitor Triggers Cell Cycle Arrest in Acute Myeloid Leukemia.ACS omega · 2025Article
- Conformational Flexibility of the C-Terminal Region Influences Distal Active Site Residues Across the Tautomerase Superfamily.International journal of molecular sciences · 2024Article
- Macrophage migration inhibitory factor as a therapeutic target in neuro-oncology: A review.Neuro-oncology advancesReview
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundMacrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that has been implicated in multiple inflammatory and non-inflammatory diseases, including liver injury induced by acetaminophen (APAP) overdose. Multiple small molecule inhibitors of MIF have been described, including the clinically available anti-rheumatic drug T-614 (iguratimod); however, this drug's mode of inhibition has not been fully investigated.
methodsWe conducted in vitro testing including kinetic analysis and protein crystallography to elucidate the interactions between MIF and T-614. We also performed in vivo experiments testing the efficacy of T-614 in a murine model of acetaminophen toxicity. We analyzed survival in lethal APAP overdose with and without T-614 and using two different dosing schedules of T-614. We also examined MIF and MIF inhibition effects on hepatic hydrogen peroxide (H
resultsKinetic analysis was consistent with a non-competitive type of inhibition and an inhibition constant (K
conclusionsT-614 is an allosteric inhibitor of MIF that prevented death and decreased hepatic hydrogen peroxide concentrations when given prophylactically in a murine model of acetaminophen overdose. Further studies are needed to elucidate the mechanistic role of MIF in APAP toxicity.
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Registered trials
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