C-DIM12 is characterized as a potent and orally efficacious antagonist of Nurr1, known for suppressing tumor proliferation and autophagy while promoting cell apoptosis. It exhibits both anti-inflammatory and neuroprotective properties, making it suitable for research in cancer and neurological disorders. Through its actions, C-DIM12 mitigates tumor growth and cellular self-digestion processes and encourages cell programmed death, contributing to its utility in scientific investigations related to oncology and neurology1].[2].[3].
体内研究
When given intraperitoneally at 25 mg/kg for 14 days, it adjusts glial responsiveness in mice models of MPTP-induced Parkinson's disease[2].
Furthermore, with a dosage of 50-100 mg/kg administered intraperitoneally thrice, it lessens brain inflammation and aids in functional recuperation post-intracerebral hemorrhage in mice.
At 30 mg/kg for 30 days via the same route, C-DIM12 hampers the growth of tumors and autophagy, while inducing apoptosis in NURR1-KO cells within orthotopic xenografts[1].
体外研究
Administering C-DIM12 at a concentration of 15 μM for a duration of 3-5 days enhances both proliferation and survival rates of MiaPaCa2 cells by impeding autophagic processes[1].
C-DIM12 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Primary murine synovial fibroblasts
10 µM
1 hour pretreatment followed by 12 hours
C-DIM12 suppressed TNF α-induced VCAM-1 and ICAM-1 expression and reduced PGE2 and COX-2 production.
Mol Immunol. 2018 Sep;101:46-54.
PC12 cells
0–20 µM
18 hours
C-DIM12 activated NR4A2-dependent transactivation in PC12 cells, indicating its action through Nurr1.
J Pharmacol Exp Ther. 2018 Jun;365(3):636-651.
BV-2 cells
10 µM
24 hours
Increased CB2 receptor mRNA level
Acta Pharmacol Sin. 2022 Sep;43(9):2253-2266.
Primary microglia
10 µM
24 hours
Enhanced nuclear translocation of Nurr1 and suppressed LPS-induced IL-6 and NOS2 expression.
Mol Pharmacol. 2015 Jun;87(6):1021-34.
NF-κB-GFP HEK293 reporter cells
100 µM
24 hours
Reduced TNFα-induced NF-κB activation, comparable to the positive control Bay-11.
Mol Pharmacol. 2015 Jun;87(6):1021-34.
BV-2 microglia
10 µM
24 hours
Inhibited LPS-induced expression of NF-κB-regulated genes (e.g., NOS2, IL-6, CCL2), with effects attenuated by Nurr1-RNA interference.
Mol Pharmacol. 2015 Jun;87(6):1021-34.
SH-SY5Y cells
10 µM
72 hours
C-DIM12 significantly increased SYNGR3 protein expression
Int J Mol Sci. 2022 Mar 26;23(7):3646.
C-DIM12 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6J mice
Young mice
Oral gavage
10, 35 or 100 mg/kg
Young mice: single dose; aged mice: 5 consecutive days
C-DIM12 enhances long-term spatial memory in young mice and rescues memory deficits in aged mice.
Neurobiol Aging. 2020 Jan;85:140-144
C57BL/6 mice
MPTP-induced Parkinson's disease model
Oral gavage
25 mg/kg
Once daily for 14 days
C-DIM12 protected dopaminergic neurons in the substantia nigra pars compacta, reduced microglial and astrocytic activation, and improved motor function.
J Pharmacol Exp Ther. 2018 Jun;365(3):636-651.
C57BL/6J mice
Aged mice
Oral gavage
35 mg/kg
Young mice: single dose; aged mice: 5 consecutive days
C-DIM12 enhances long-term spatial memory in young mice and rescues memory deficits in aged mice.
Neurobiol Aging. 2020 Jan;85:140-144
Transgenic NF-κB/EGFP reporter mice
MPTP and probenecid-induced Parkinson's disease model
Oral gavage
50 mg/kg
Once daily for 7 days
C-DIM12 had the greatest neuroprotective activity in MPTPp-treated mice, and was also the most potent compound in suppressing activation of microglia and astrocytes, expression of cytokines and chemokines in quantitative polymerase chain reaction (qPCR) array studies, and in reducing expression of NF-κB/EGFP in the SN. C-DIM12 prevented nuclear export of Nurr1 in dopaminergic neurons and enhanced expression of the Nurr1-regulated proteins tyrosine hydroxylase and the dopamine transporter.
Toxicol Sci. 2015 Feb;143(2):360-73
C57BL/6 mice
Parkinson’s disease model
Oral
50 mg/kg
Once daily for 7 days
Oral administration of C-DIM12 after one week of exposure to MPTP and probenecid prevented further loss of dopaminergic neurons in the substantia nigra pars compacta and striatal dopamine terminals, indicating that these compounds could be effective therapeutic agents to prevent neurodegeneration.
J Pharmacol Exp Ther. 2013 Apr;345(1):125-38
ICR mice
Intracerebral hemorrhage model
Oral
50 or 100 mg/kg
Once daily for three days
C-DIM12 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. In addition, C-DIM12 as well as amodiaquine preserved axonal structures in the internal capsule and axonal transport function.
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