Nurr1/RXR dual agonist 1 is a dual activator of Nurr1 ( EC 50 = 2.6 µM) and RXR with K [1] s of 0.6 and 1.1 µM, respectively. Nurr1/RXR dual agonist 1 exclusively activates the heterodimer response element DR5 by selectively destabilizing the Nurr1 homodimer and stabilizing the Nurr1:RXR heterodimer. Nurr1/RXR dual agonist 1 enhances expression of a specific subset of neuroprotective Nurr1 target genes while avoiding induction of genes associated with potential off-target effects in neuronal cells. Nurr1/RXR dual agonist 1 can be used for neurodegenerative diseases research [1].
In Vitro, Nurr1/RXR agonist 1 (compound 2) (15 h) induces a considerable 3.3-fold activation of Nurr1, with both Nurr1 and RXR involved[1]. Nurr1/RXR dual agonist 1 (30 μM) diminishes Nurr1 homodimer formation while leaving the Nurr1:RXR heterodimer intact[1]. Nurr1/RXR agonist 1 (0.3-30 μM) enhances DR5-dependent transcription but does not activate NBRE or NurRE[1]. Nurr1/RXR agonist 1 (0.3-30 μM, 24 h) exhibits no toxic effect in HEK293T cells[1]. Nurr1/RXR agonist 1 (10 μM, 21 h) achieves differential modulation or functional selectivity in activating downstream gene expression programs in rat dopaminergic neurons[1]. Nurr1/RXR agonist 1 induces genes that have a higher empirical probability of containing DR5 elements in their promoter regions[1].
References:
[1]. Scholz K, et al. Dual Nurr1/RXR agonism of valerenic acid and synthetic mimetics enables dimer-selective Nurr1 modulation. ACS Med Chem Lett. 2026 Jan 8;17(1):170-174.
In Vitro, Nurr1/RXR agonist 1 (compound 2) (15 h) induces a considerable 3.3-fold activation of Nurr1, with both Nurr1 and RXR involved[1]. Nurr1/RXR dual agonist 1 (30 μM) diminishes Nurr1 homodimer formation while leaving the Nurr1:RXR heterodimer intact[1]. Nurr1/RXR agonist 1 (0.3-30 μM) enhances DR5-dependent transcription but does not activate NBRE or NurRE[1]. Nurr1/RXR agonist 1 (0.3-30 μM, 24 h) exhibits no toxic effect in HEK293T cells[1]. Nurr1/RXR agonist 1 (10 μM, 21 h) achieves differential modulation or functional selectivity in activating downstream gene expression programs in rat dopaminergic neurons[1]. Nurr1/RXR agonist 1 induces genes that have a higher empirical probability of containing DR5 elements in their promoter regions[1].
References:
[1]. Scholz K, et al. Dual Nurr1/RXR agonism of valerenic acid and synthetic mimetics enables dimer-selective Nurr1 modulation. ACS Med Chem Lett. 2026 Jan 8;17(1):170-174.