ArticleJournal of medicinal chemistry2026
Structural Tuning of Vidofludimus for High-Efficacy NR4A Agonism.
Article in Journal of medicinal chemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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7 authors.
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Abstract
The nerve growth factor IB-like receptors (NR4A) are (neuro)protective transcription factors as part of the immediate early response and hold potential in various pathologies, including neurodegeneration. Despite recent progress in NR4A ligand development, high-quality chemical tools to probe phenotypic effects of NR4A modulation are still rare, and a selective agonist with strong efficacy is lacking. Here, we developed a potent and selective NR4A activator equipped with distinctly high agonist efficacy building on the scaffold of the dihydroorotate dehydrogenase inhibitor and nuclear receptor-related 1 agonist vidofludimus. We identified structural modifications conveying potency, selectivity, and efficacy via systematic structure-activity relationship elucidation, and fusion of favored motifs eventually enabled multiparameter optimization to a chemical tool meeting highest quality criteria for biological studies.
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