Nurr1/RXR dual agonist 1 is a dual activator of Nurr1 (EC50 = 2.6 µM) and RXR, with Ks values of 0.6 and 1.1 µM, respectively. It disrupts the stability of Nurr1 homodimers selectively while stabilizing Nurr1:RXR heterodimers, specifically activating the heterodimer response element DR5. In neuronal cells, Nurr1/RXR dual agonist 1 enhances the expression of neuroprotective Nurr1 target genes without inducing genes associated with off-target effects. This compound is applicable in studies related to neurodegenerative diseases.

Nurr1/RXR agonist 1 (compound 2) (15 h) significantly mediates Nurr1 activation by 3.3-fold and is effective for both Nurr1 and RXR. At a concentration of 10 μM, it reduces the formation of Nurr1 homodimers while preserving the integrity of the Nurr1:RXR heterodimer. Within the range of 0.3-30 μM, it enhances DR5-dependent transcription without activating NBRE or NurRE. Additionally, at concentrations between 3-30 μM over 24 hours, it shows no toxic effects in HEK293T cells. At 10 μM for 21 hours, it achieves differential regulation or functional selective activation of downstream gene expression in rat dopaminergic neurons. The genes induced by Nurr1/RXR agonist 1 are more likely to contain DR5 elements in their promoter regions.