C-DIM12
C-DIM12 Basic information
- Product Name:
- C-DIM12
- Synonyms:
-
- C-DIM12
- C-DIM12(1,1-bis (3'-indolyl)-1-(p-chlorophenyl) methane)
- C-DIMI2
- 3,3'-[(4-chlorophenyl)methylene]bis-1H-Indole
- C-DIM12, 178946-89-9
- C-DIM12 (C-DIM-12
- CS-2311
- C-DIM12, >98%
- CAS:
- 178946-89-9
- MF:
- C23H17ClN2
- MW:
- 356.85
- Mol File:
- 178946-89-9.mol
C-DIM12 Chemical Properties
- Melting point:
- 76-77 °C
- Boiling point:
- 585.6±45.0 °C(Predicted)
- Density
- 1.324±0.06 g/cm3(Predicted)
- storage temp.
- 2-8°C(protect from light)
- solubility
- Soluble in DMSO (up to 35 mg/ml) or in Ethanol (up to 35 mg/ml)
- form
- solid
- pka
- 16.40±0.30(Predicted)
- color
- Orange
- Stability:
- Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 2 months.
- 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
- InChIKey
- LTLRXTDMXOFBDW-UHFFFAOYSA-N
- SMILES
- ClC(C=C1)=CC=C1C(C2=CNC3=C2C=CC=C3)C4=CNC5=C4C=CC=C5
C-DIM12 Usage And Synthesis
Description
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.
Uses
C-DIM12 is a potent, orally active Nurr1 antagonist. C-DIM12 inhibits the tumor growth and autophagy, and induces the cell apoptosis. C-DIM12 has anti-inflammatory and neuroprotective effects, and can be used for cancer and neurological disease study[1][2][3].
in vivo
C-DIM12 (25 mg/kg for i.p., 14 day) modulates glial reactivity in MPTP-Induced Parkinsonism mice[2].
C-DIM12 (50-100 mg/kg for i.p., three times ) attenuates brain inflammation and improves functional recovery after intracerebral hemorrhage in mice[3].
C-DIM12 (30 mg/kg for i.p., 30 day) inhibits tumor growth and autophagy, and induces apoptosis in NURR1-KO cells orthotopic xenograft[1].
Pharmacokinetic Analysis in C57BL/6 male mice[1]
| Route | Organ | Dose (mg/kg) | Area under Curve (ng/mL*min) | t1/2 (min) | Cmax (ng/mL) |
| i.g. | Plasma | 25 | 539,220 | 249 | 1120 |
| i.g. | Brain | 25 | 2,273,711 | 265 | 3622 |
| Animal Model: | MPTP-induced C57BL/6 male Parkinsonism mice [2] |
| Dosage: | 25 mg/kg/day, 14day |
| Administration: | Intragastric gavage (i.g.) |
| Result: | 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. |
| Animal Model: | The ICR mice model of intracerebral hemorrhage induced by collagenase type VII[3] |
| Dosage: | 50 and 100mg/kg/day at a 24-h interval, three times |
| Administration: | Orally administration |
| Result: | Improved the recovery of neurological function and prevented neuron loss in the hematoma, while suppressed activation of microglia/macrophages and expression of inflammatory mediators interleukin-6 and CC chemokine ligand 2. Preserved axonal structures in the internal capsule and axonal transport function. Decreased of iNOS mRNA expression. |
| Animal Model: | MiaPaCa2 cells (Ctrl and NURR1-KO) orthotopic xenograft tumor models[1] |
| Dosage: | 30 mg/kg, 30 day |
| Administration: | Intraperitoneal injection (i.p.) |
| Result: | Inhibited tumor growth and ATG7 and ATG12 mRNA levels, and induced apoptosis. |
IC 50
Nurr1/NR4A2
storage
Store at -20°C
References
[1] TERUO INAMOTO. 1,1-Bis(3’-indolyl)-1-(p-chlorophenyl)methane activates the orphan nuclear receptor Nurr1 and inhibits bladder cancer growth.[J]. Molecular Cancer Therapeutics, 2008: 3825-3833. DOI:10.1158/1535-7163.mct-08-0730
[2] XI LI Stephen S Syng Ook Lee. Structure-dependent activation of NR4A2 (Nurr1) by 1,1-bis(3′-indolyl)-1-(aromatic)methane analogs in pancreatic cancer cells[J]. Biochemical pharmacology, 2012, 83 10: Pages 1445-1455. DOI:10.1016/j.bcp.2012.02.021
[3] BRIANA R DE MIRANDA. 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.[J]. Molecular Pharmacology, 2015, 87 6: 1021-1034. DOI:10.1124/mol.114.095398
[4] Neuroprotective efficacy and pharmokinetic behavior of novel anti-inflammatory para phenyl substituted diindolylmethanes ina a mouse model of Parkinson’s disease
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