ArticleJournal of the American Chemical Society2015
Design, synthesis, and protein crystallography of biaryltriazoles as potent tautomerase inhibitors of macrophage migration inhibitory factor.
Article in Journal of the American Chemical Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Identification of a novel and high affinity MIF inhibitorJournal of enzyme inhibition and medicinal chemistry · 2025Article
- Targeting secretory autophagy in solid cancers: mechanisms, immune regulation and clinical insights.Experimental hematology & oncology · 2025Review
- Elevated levels of IRF1 and CASP1 as pyroptosis-related biomarkers for intestinal epithelial cells in Crohn's disease.Frontiers in immunology · 2025Article
- Recent trends for chemoselectivity modulation in one-pot organic transformations.RSC advances · 2024Review
- Allosteric Inhibitors of Macrophage Migration Inhibitory Factor (MIF) Interfere with Apoptosis-Inducing Factor (AIF) Co-Localization to Prevent Parthanatos.Journal of medicinal chemistry · 2023Article
- Comparison of Receptor-Ligand Restraint Schemes for Alchemical Absolute Binding Free Energy Calculations.Journal of chemical theory and computation · 2023Article
- Thieno[2,3-Journal of medicinal chemistry · 2022Article
- Macrophage migration inhibitory factor family proteins are multitasking cytokines in tissue injury.Cellular and molecular life sciences : CMLS · 2022Review
- An open-source molecular builder and free energy preparation workflow.Communications chemistry · 2022Article
- Enzymatic synthesis of fluorinated compounds.Applied microbiology and biotechnology · 2021Review
- Bifunctional small molecules that mediate the degradation of extracellular proteins.Nature chemical biology · 2021Article
- Proteolysis Targeting Chimera (PROTAC) for Macrophage Migration Inhibitory Factor (MIF) Has Anti-Proliferative Activity in Lung Cancer Cells.Angewandte Chemie (International ed. in English) · 2021Article
- 7-Hydroxycoumarins Are Affinity-Based Fluorescent Probes for Competitive Binding Studies of Macrophage Migration Inhibitory Factor.Journal of medicinal chemistry · 2020Article
- Inhibition of Macrophage Migration Inhibitory Factor by a Chimera of Two Allosteric Binders.ACS medicinal chemistry letters · 2020Article
- Absolute Free Energy of Binding Calculations for Macrophage Migration Inhibitory Factor in Complex with a Druglike Inhibitor.The journal of physical chemistry. B · 2019Article
- Robust Free Energy Perturbation Protocols for Creating Molecules in Solution.Journal of chemical theory and computation · 2019Article
- A toll-like receptor agonist mimicking microbial signal to generate tumor-suppressive macrophages.Nature communications · 2019Article
- Small-molecule inhibitors of macrophage migration inhibitory factor (MIF) as an emerging class of therapeutics for immune disorders.Drug discovery today · 2018Review
- Advances and Insights for Small Molecule Inhibition of Macrophage Migration Inhibitory Factor.Journal of medicinal chemistry · 2018Article
- Optimization of Pyrazoles as Phenol Surrogates to Yield Potent Inhibitors of Macrophage Migration Inhibitory Factor.ChemMedChem · 2018Article
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Authors and funding
7 authors.
Funding
Abstract
Optimization is reported for biaryltriazoles as inhibitors of the tautomerase activity of human macrophage migration inhibitory factor (MIF), a proinflammatory cytokine associated with numerous inflammatory diseases and cancer. A combined approach was taken featuring organic synthesis, enzymatic assaying, crystallography, and modeling including free-energy perturbation (FEP) calculations. X-ray crystal structures for 3a and 3b bound to MIF are reported and provided a basis for the modeling efforts. The accommodation of the inhibitors in the binding site is striking with multiple hydrogen bonds and aryl-aryl interactions. Additional modeling encouraged pursuit of 5-phenoxyquinolinyl analogues, which led to the very potent compound 3s. Activity was further enhanced by addition of a fluorine atom adjacent to the phenolic hydroxyl group as in 3w, 3z, 3aa, and 3bb to strengthen a key hydrogen bond. It is also shown that physical properties of the compounds can be modulated by variation of solvent-exposed substituents. Several of the compounds are likely the most potent known MIF tautomerase inhibitors; the most active ones are more than 1000-fold more active than the well-studied (R)-ISO-1 and more than 200-fold more active than the chromen-4-one Orita-13.
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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.