C-DIM5 is a para-phenyl-substituted diindolylmethane (C-DIM) and an agonist of the orphan receptor nuclear receptor-related protein 77 (Nur77).1 It selectively activates Nur77 over peroxisome proliferator receptor γ (PPARγ) in reporter assays when used at a concentration of 20 μM. C-DIM5 (10, 15, and 20 μM) inhibits growth of and induces apoptosis in L3.6pL pancreatic cancer cells.2 It stabilizes nuclear localization of Nur77 and Nurr1 and reduces secretion of the pro-inflammatory cytokines IL-2, IL-6, IL-12p70, CCL2, and CCL5 in primary mouse astrocytes.3 Oral administration of C-DIM5 (50 mg/kg) prevents loss of dopaminergic neurons in the substantia nigra pars compacta and striatal dopamine terminals in a mouse model of Parkinson's disease induced by MPTP.4
1.Chintharlapalli, S., Burghardt, R., Papineni, S., et al.Activation of Nur77 by selected 1,1-Bis(3'-indolyl)-1-(p-substituted phenyl)methanes induces apoptosis through nuclear pathwaysJ. Biol. Chem.280(26)24903-24914(2005) 2.Yoon, K., Lee, S.O., Cho, S.D., et al.Activation of nuclear TR3 (NR4A1) by a diindolylmethane analog induces apoptosis and proapoptotic genes in pancreatic cancer cells and tumorsCarcinogenesis32(6)836-842(2011) 3.Popichak, K.A., Hammond, S.L., Moreno, J.A., et al.Compensatory expression of Nur77 and Nurr1 regulates NF-κB-dependent inflammatory signaling in astrocytesMol. Pharmacol.94(4)1174-1186(2018) 4.De Miranda, B.R., Miller, J.A., Hansen, R.J., et al.Neuroprotective efficacy and pharmacokinetic behavior of novel anti-inflammatory para-phenyl substituted diindolylmethanes in a mouse model of Parkinson's diseaseJ. Pharmacol. Exp. Ther.345(1)125-138(2013)