DIM-C-pPhOCH3
(Synonyms: DIM-C-pPhOCH3) 目录号 : GC32884
A Nur77 receptor agonist
Cas No.:33985-68-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | RKO cells are treated with DMSO or 12.5 μM DIM-C-pPhOCH3 for 2 and 6 h. RNA is isolated for the reverse transcription-PCR (RT-PCR) experiment and analyzed for gene expression, and three replicates are determined for each time point and the DMSO control. The microarray data are analyzed[1]. |
Animal experiment: | Mice[1]Male athymic nude mice (Foxn1nu, ages 7-8 weeks) are used. The mice are housed and maintained in laminar flow cabinets under specific pathogen-free conditions. A xenograft is established by s.c. injection of in vitro cultured RKO cells (5×106 per 150 μL) into the flanks of individual mice. Tumors are allowed to grow for 4 days until tumors are palpable. Mice are then randomized into two groups of six mice per group and dosed by oral gavage with either corn oil or 25 mg/kg/d DIM-C-pPhOCH3 for 21 days. The mice are weighed, and tumor size is measured[1]. |
References: [1]. Cho SD, et al. Nur77 agonists induce proapoptotic genes and responses in colon cancer cells through nuclear receptor-dependent and nuclear receptor-independent pathways. Cancer Res. 2007 Jan 15;67(2):674-83. | |
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)
| Cas No. | 33985-68-1 | SDF | |
| 别名 | DIM-C-pPhOCH3 | ||
| Canonical SMILES | COC1=CC=C(C(C2=CNC3=C2C=CC=C3)C4=CNC5=C4C=CC=C5)C=C1 | ||
| 分子式 | C24H20N2O | 分子量 | 352.43 |
| 溶解度 | DMSO : ≥ 33.3 mg/mL (94.49 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.8374 mL | 14.1872 mL | 28.3744 mL |
| 5 mM | 0.5675 mL | 2.8374 mL | 5.6749 mL |
| 10 mM | 0.2837 mL | 1.4187 mL | 2.8374 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
1,1-Bis (3'-indolyl)-1-(p-substitutedphenyl)methane compounds inhibit lung cancer cell and tumor growth in a metastasis model
Eur J Pharm Sci 2013 Oct 9;50(2):227-41.PMID:23892137DOI:10.1016/j.ejps.2013.07.007.
1,1-Bis(3-indolyl)-1-(p-substitutedphenyl)methane (C-DIM) compounds exhibit remarkable antitumor activity with low toxicity in various cancer cells including lung tumors. Two C-DIM analogs, DIM-C-pPhOCH3 (C-DIM-5) and DIM-C-pPhOH (C-DIM-8) while acting differentially on the orphan nuclear receptor, TR3/Nur77 inhibited cell cycle progression from G0/G1 to S-phase and induced apoptosis in A549 cells. Combinations of docetaxel (doc) with C-DIM-5 or C-DIM-8 showed synergistic anticancer activity in vitro and these results were consistent with their enhanced antitumor activities invivo. Respirable aqueous formulations of C-DIM-5 (mass median aerodynamic diameter of 1.92±0.22μm and geometric standard deviation of 2.31±0.12) and C-DIM-8 (mass median aerodynamic diameter of 1.84±0.31μm and geometric standard deviation of 2.11±0.15) were successfully delivered by inhalation to athymic nude mice bearing A549 cells as metastatic tumors. This resulted in significant (p<0.05) lung tumor regression and an overall reduction in tumor burden. Analysis of lung tumors from mice treated with inhalational formulations of C-DIM-5 and C-DIM-8 showed decreased mRNA and protein expression of mediators of tumor initiation, metastasis, and angiogenesis including MMP2, MMP9, c-Myc, β-catenin, c-Met, c-Myc, and EGFR. Microvessel density assessment of lung tissue sections showed significant reduction (p<0.05) in angiogenesis and metastasis as evidenced by decreased distribution of immunohistochemical staining of VEGF, and CD31. Our studies demonstrate both C-DIM-5 and C-DIM-8 have similar anticancer profiles in treating metastatic lung cancer and possibly work as TR3 inactivators.
Nur77 agonists induce proapoptotic genes and responses in colon cancer cells through nuclear receptor-dependent and nuclear receptor-independent pathways
Cancer Res 2007 Jan 15;67(2):674-83.PMID:17234778DOI:10.1158/0008-5472.CAN-06-2907.
Nerve growth factor-induced Balpha (NGFI-Balpha, Nur77) is an orphan nuclear receptor with no known endogenous ligands; however, recent studies on a series of methylene-substituted diindolylmethanes (C-DIM) have identified 1,1-bis(3'-indolyl)-1-(phenyl)methane (DIM-C-Ph) and 1,1-bis(3'-indolyl)-1-(p-anisyl)methane (DIM-C-pPhOCH3) as Nur77 agonists. Nur77 is expressed in several colon cancer cell lines (RKO, SW480, HCT-116, HT-29, and HCT-15), and we also observed by immunostaining that Nur77 was overexpressed in colon tumors compared with normal colon tissue. DIM-C-Ph and DIM-C-pPhOCH3 decreased survival and induced apoptosis in RKO colon cancer cells, and this was accompanied by induction of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein. The induction of apoptosis and TRAIL by DIM-C-pPhOCH3 was significantly inhibited by a small inhibitory RNA for Nur77 (iNur77); however, it was evident from RNA interference studies that DIM-C-pPhOCH3 also induced Nur77-independent apoptosis. Analysis of DIM-C-pPhOCH3-induced gene expression using microarrays identified several proapoptotic genes, and analysis by reverse transcription-PCR in the presence or absence of iNur77 showed that induction of programmed cell death gene 1 was Nur77 dependent, whereas induction of cystathionase and activating transcription factor 3 was Nur77 independent. DIM-C-pPhOCH3 (25 mg/kg/d) also inhibited tumor growth in athymic nude mice bearing RKO cell xenografts. These results show that Nur77-active C-DIM compounds represent a new class of anti-colon cancer drugs that act through receptor-dependent and receptor-independent pathways.
p21 expression is induced by activation of nuclear nerve growth factor-induced Balpha (Nur77) in pancreatic cancer cells
Mol Cancer Res 2009 Jul;7(7):1169-78.PMID:19584258DOI:10.1158/1541-7786.MCR-08-0473.
1,1-Bis(3'-indolyl)-1-(p-anisyl)methane (DIM-C-pPhOCH3) activates the orphan receptor nerve growth factor-induced Balpha (Nur77) in cancer cells, and in this study, DIM-C-pPhOCH3 decreased Panc1 pancreatic cancer cell survival and arrested cells in G0-G1. These responses were accompanied by induction of the cyclin-dependent kinase inhibitor p21 in pancreatic cancer cells. Mechanistic studies showed that induction of p21 mRNA and protein by DIM-C-pPhOCH3 was Nur77 dependent but did not depend on Krüppel-like factor 4, which was also induced by DIM-C-pPhOCH3. Activation of p21 promoter constructs by DIM-C-pPhOCH3 required the GC-rich proximal region of the promoter, and results of RNA interference studies showed that Nur77-dependent activation of the p21 promoter involved interactions with Sp1 and Sp4 but not Sp3. Interactions of Nur77 with the p21 promoter in Panc1 cells treated with DIM-C-pPhOCH3 were also confirmed in chromatin immunoprecipitation assays. These data show that activation of nuclear Nur77 results in a novel pathway for induction of p21, which is independent of Nur77 response elements but dependent on Sp proteins bound to the GC-rich proximal region of the p21 promoter.