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Nurr1 ligands have been developed as tools to capture the receptor's potential in vitro and in vivo, but a dedicated brain\u2010targeting agonist has been lacking. Here, we employed the scaffold of the dihydroorotate dehydrogenase (DHODH) inhibitor and strong Nurr1 activator vidofludimus to develop a descendant with a high brain\u2010to\u2010blood ratio. 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