Allosteric Inhibitors of Macrophage Migration Inhibitory Factor (MIF) Interfere with Apoptosis-Inducing Factor (AIF) Co-Localization to Prevent Parthanatos.
Journal
Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531
Informations de publication
Date de publication:
13 07 2023
13 07 2023
Historique:
medline:
14
7
2023
pubmed:
23
6
2023
entrez:
23
6
2023
Statut:
ppublish
Résumé
Macrophage migration inhibitory factor (MIF) is a multifunctional cytokine and essential signaling protein associated with inflammation and cancers. One of the newly described roles of MIF is binding to apoptosis-inducing factor (AIF) that "brings" cells to death in pathological conditions. The interaction between MIF and AIF and their nuclear translocation stands as a central event in parthanatos. However, classical competitive MIF tautomerase inhibitors do not interfere with MIF functions in parthanatos. In this study, we employed a pharmacophore-switch to provide allosteric MIF tautomerase inhibitors that interfere with the MIF/AIF co-localization. Synthesis and screening of a focused compound collection around the 1,2,3-triazole core enabled identification of the allosteric tautomerase MIF inhibitor
Identifiants
pubmed: 37352470
doi: 10.1021/acs.jmedchem.3c00397
pmc: PMC10350922
doi:
Substances chimiques
Macrophage Migration-Inhibitory Factors
0
Apoptosis Inducing Factor
0
MIF protein, human
EC 5.3.2.1
Intramolecular Oxidoreductases
EC 5.3.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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