C-DIM12 is a novel synthetic activator of Nurr1. C-DIM12 induces dopaminergic gene expression and protects against 6-hydroxydopamine neurotoxicity in vitro. C-DIM12 activates Nurr1 in cancer cells and prevents loss of dopaminergic neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD in mice. C-DIM12 induced expression of Nurr1-regulated genes that was abolished by Nurr1 knockdown. C-DIM12 increased expression of transfected human Nurr1, induced Nurr1 protein expression in primary dopaminergic neurons and enhanced neuronal survival from exposure to 6-OHDA. C-DIM12 stimulates neuroprotective expression Nurr1-regulated genes in DA neurons.