4A7C-301 is a potent, selective, brain-penetrant agonist of nuclear receptor Nurr1 with EC50 of 6.53 uM, binds to Nurr1 ligand binding domain (LBD) with IC50 of 50 nM.
4A7C-301 shows higher potency than chloroquine (CQ), exhibits approximately 50 times higher potency than CQ in N27-A cells (EC50= ~0.2 and ~10  µM, respectively).
4A7C-301 selectively activates the transcriptional activity of Nurr1, but not Nur77, over Nor1.
4A7C-301 induces Nurr1's transcriptional activity with the greatest potency (13-14 fold) among NR4A members in SK-N-BE(2)C cells.
4A7C-301 restores Nurr1 protein expression levels that are diminished by exposure to environmental and genetic risk factors of PD in vitro.
4A7C-301 suppresses neuroinflammation in ventral mesencephalic (VM) neuron-glia co-cultures.
4A7C-301 restores autophagy against MPP+ in vitro.
4A7C-301 (5 mg/kg/day) 4A7C-301 protects midbrain dopamine neurons in the MPTP-induced male mouse model of PD and improves both motor and non-motor olfactory deficits without dyskinesia-like behaviors.
4A7C-301 also significantly ameliorates neuropathological abnormalities and improves motor and olfactory dysfunctions in AAV2-mediated α-synuclein-overexpressing male mouse models.