NR4A agonist-2

NR4A agonist-2, derived from the design of Vidofludimus, is a selective pan-NR4A agonist with a dissociation constant (Kd) of 0.10 μM for NR4A1 and half-maximal effective concentrations (EC50) of 0.098 μM, 0.092 μM, and 0.09 μM for Nur77, Nurr1, and NOR-1, respectively. It exhibits 47-fold selectivity for DHODH and demonstrates no cytotoxic activity at concentrations up to 10 μM. NR4A agonist-2 acts by binding to a specific surface pocket in the ligand-binding domain of Nurr1, inhibiting Nurr1 homodimer formation and activating response elements such as NBRE, NurRE, and DR5, thus robustly inducing the expression of neuroprotective genes like BDNF and SOD2. This compound holds potential for research in neurodegenerative diseases including Parkinson's disease, dementia, and multiple sclerosis.