178946-89-9

C-DIM12 is a para-phenyl-substituted diindolylmethane (C-DIM) that is an orally bioavailable activator of nuclear receptor-related protein 1 (Nurr1/NR4A2). It is selective for Nurr1, not activating Nur77, neuron-derived orphan receptor 1 (Nor1), or the retinoid X receptor (RXR) in parallel luciferase assays. C-DIM12 (2.5-10 μM) inhibits proliferation of Ku7 and 253J B-V bladder cancer cells in a dose-dependent manner and induces apoptosis of KU7 cells in a Nurr1-dependent manner. In an orthotopic nude mouse model, C-DIM12 suppresses bladder cancer cell growth by 44 and 59% at doses of 12.5 and 25 mg/kg, respectively. C-DIM12 has neuroprotective properties, preventing dopaminergic cell loss and reducing the expression of NF-κB in the substantia nigra pars compacta in an MPTP mouse model of Parkinson’s disease. It also has analgesic and anti-inflammatory activity in the tail immersion and carrageenan paw edema assays at a dose of 100 mg/kg, without causing ulcers in rats.

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1) Inamoto et al. (2008), 1,1-Bis(3’-indolyl)-1-(p-chlorophenyl)methane activates the orphan nuclear receptor Nurr1 and inhibits bladder cancer growth; Mol Cancer Ther., 7 3825 2) Li et al. (2012), Structure-dependent activation of NR4A2 (Nurr1) by 1,1-bis(3’-indoyl)-1-(aromatic)methane analogs in pancreatic cancer cells; Biochem. Pharmacol., 83 1445 3) De Miranda et al. (2015), The Nurr1 Activator 1,1-Bis(3’-Indolyl)-1-(p-chlorophenyl)Methane blocks Inflammatory Gene Expression in BV-2 Microglial Cells by Inhibiting Nuclear Factor kB; Mol. Pharmacol., 87 1021 4) De Miranda et al. (2013), Neuroprotective efficacy and pharmokinetic behavior of novel anti-inflammatory para phenyl substituted diindolylmethanes ina a mouse model of Parkinson’s disease; J. Pharmacol. Exp. Ther., 345 125