C-DIM12
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MedKoo CAT#: 522683

CAS#: 178946-89-9

Description: 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.


Chemical Structure

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C-DIM12
CAS# 178946-89-9

Theoretical Analysis

MedKoo Cat#: 522683
Name: C-DIM12
CAS#: 178946-89-9
Chemical Formula: C23H17ClN2
Exact Mass: 356.11
Molecular Weight: 356.853
Elemental Analysis: C, 77.41; H, 4.80; Cl, 9.93; N, 7.85

Price and Availability

Size Price Availability Quantity
50mg USD 250
100mg USD 450
200mg USD 650
500mg USD 1250
1g USD 1850
5g USD 4250
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Synonym: C-DIM12; C-DIM 12; C-DIM-12.

IUPAC/Chemical Name: 1,1-bis(3-indolyl)-1-(p-chlorophenyl)methane

InChi Key: LTLRXTDMXOFBDW-UHFFFAOYSA-N

InChi Code: InChI=1S/C23H17ClN2/c24-16-11-9-15(10-12-16)23(19-13-25-21-7-3-1-5-17(19)21)20-14-26-22-8-4-2-6-18(20)22/h1-14,23,25-26H

SMILES Code: ClC1=CC=C(C(C2=CNC3=C2C=CC=C3)C4=CNC5=C4C=CC=C5)C=C1

Appearance: Light Brown solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Product Data:
Biological target: C-DIM12 is Nurr1 activator that stimulates Nurr1 mediated apoptosis axis in bladder cancer cells and tumors and inhibits NF-κB–dependent gene expression in glial cells.
In vitro activity: The synthetic, phytochemical-based compound, 1,1-bis (3'-indolyl)-1-(p-chlorophenyl) methane (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. In the present study, we examined the capacity of C-DIM12 to induce expression of Nurr1-regulated genes in two dopaminergic neuronal cell lines (N2A, N27) and to protect against 6-hydroxydopamine (6-OHDA) neurotoxicity. 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. These data indicate that C-DIM12 stimulates neuroprotective expression Nurr1-regulated genes in DA neurons. Reference: Neurosci Lett. 2015 Oct 21;607:83-89. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/26383113/
In vivo activity: Pharmacokinetic analysis of C-DIM12 in mice by liquid chromatography-mass spectrometry demonstrated that approximately three times more compound concentrated in the brain than in plasma. Mice treated with four doses of MPTP + probenecid over 14 days were monitored for neurobehavioral function, loss of dopaminergic neurons, and glial activation. C-DIM12 protected against the loss of DA neurons in the substantia nigra pars compacta and DA terminals in the striatum, maintained a ramified phenotype in microglia, and suppressed activation of astrocytes. In vitro reporter assays demonstrated that C-DIM12 was an effective activator of Nurr1 transcription in neuronal cell lines. Computational modeling of C-DIM12 binding to the three-dimensional structure of human Nurr1 identified a high-affinity binding interaction with Nurr1 at the coactivator domain. Taken together, these data suggest that C-DIM12 is an activator of Nurr1 that suppresses glial activation and neuronal loss in vivo after treatment with MPTP, and that this receptor could be an efficacious target for disease modification in individuals with Parkinson's disease and related disorders. Reference: J Pharmacol Exp Ther. 2018 Jun;365(3):636-651. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/29626009/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 100.0 280.23

Preparing Stock Solutions

The following data is based on the product molecular weight 356.85 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
In vitro protocol: 1. Hammond SL, Safe S, Tjalkens RB. A novel synthetic activator of Nurr1 induces dopaminergic gene expression and protects against 6-hydroxydopamine neurotoxicity in vitro. Neurosci Lett. 2015 Oct 21;607:83-89. doi: 10.1016/j.neulet.2015.09.015. Epub 2015 Sep 14. PMID: 26383113; PMCID: PMC4631643. 2. De Miranda BR, Popichak KA, Hammond SL, Jorgensen BA, Phillips AT, Safe S, Tjalkens RB. 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 κB. Mol Pharmacol. 2015 Jun;87(6):1021-34. doi: 10.1124/mol.114.095398. Epub 2015 Apr 9. PMID: 25858541; PMCID: PMC4429718.
In vivo protocol: 1. Hammond SL, Popichak KA, Li X, Hunt LG, Richman EH, Damale PU, Chong EKP, Backos DS, Safe S, Tjalkens RB. The Nurr1 Ligand,1,1-bis(3'-Indolyl)-1-(p-Chlorophenyl)Methane, Modulates Glial Reactivity and Is Neuroprotective in MPTP-Induced Parkinsonism. J Pharmacol Exp Ther. 2018 Jun;365(3):636-651. doi: 10.1124/jpet.117.246389. Epub 2018 Apr 6. PMID: 29626009; PMCID: PMC5941193.

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1: Hammond SL, Safe S, Tjalkens RB. A novel synthetic activator of Nurr1 induces
dopaminergic gene expression and protects against 6-hydroxydopamine neurotoxicity
in vitro. Neurosci Lett. 2015 Oct 21;607:83-9. doi: 10.1016/j.neulet.2015.09.015.
Epub 2015 Sep 14. PubMed PMID: 26383113; PubMed Central PMCID: PMC4631643.


2: De Miranda BR, Popichak KA, Hammond SL, Jorgensen BA, Phillips AT, Safe S,
Tjalkens RB. 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 κB. Mol Pharmacol. 2015 Jun;87(6):1021-34. doi:
10.1124/mol.114.095398. Epub 2015 Apr 9. PubMed PMID: 25858541; PubMed Central
PMCID: PMC4429718.


3: De Miranda BR, Popichak KA, Hammond SL, Miller JA, Safe S, Tjalkens RB. Novel
para-phenyl substituted diindolylmethanes protect against MPTP neurotoxicity and
suppress glial activation in a mouse model of Parkinson's disease. Toxicol Sci.
2015 Feb;143(2):360-73. doi: 10.1093/toxsci/kfu236. Epub 2014 Nov 17. PubMed
PMID: 25406165; PubMed Central PMCID: PMC4306720.


4: De Miranda BR, Miller JA, Hansen RJ, Lunghofer PJ, Safe S, Gustafson DL,
Colagiovanni D, Tjalkens RB. Neuroprotective efficacy and pharmacokinetic
behavior of novel anti-inflammatory para-phenyl substituted diindolylmethanes in
a mouse model of Parkinson's disease. J Pharmacol Exp Ther. 2013
Apr;345(1):125-38. doi: 10.1124/jpet.112.201558. Epub 2013 Jan 14. PubMed PMID:
23318470.