ArticleBiochemical pharmacology2012
Structure-dependent activation of NR4A2 (Nurr1) by 1,1-bis(3'-indolyl)-1-(aromatic)methane analogs in pancreatic cancer cells.
Article in Biochemical pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
- Comparative Profiling and Chemogenomics Application of Chemical Tools for NR4A Nuclear Receptors.Journal of medicinal chemistry · 2025Article
- New opportunities to overcome T cell dysfunction: the role of transcription factors and how to target them.Trends in biochemical sciences · 2024Review
- Natural products and synthetic analogs as selective orphan nuclear receptor 4A (NR4A) modulators.Histology and histopathology · 2024Review
- A novel NR4A2-HuR axis promotes pancreatic cancer growth and tumorigenesis that is inhibited by NR4A2 antagonists.American journal of cancer research · 2024Article
- International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023.Pharmacological reviews · 2023Review
- Transcriptional Regulation of the Synaptic Vesicle Protein Synaptogyrin-3 (International journal of molecular sciences · 2022Article
- Nuclear receptor 4A1 (NR4A1) antagonists target paraspeckle component 1 (PSPC1) in cancer cells.Molecular carcinogenesis · 2022Article
- Orphan nuclear receptor 4A1 (NR4A1) and novel ligands.Essays in biochemistry · 2021Article
- Nuclear Receptor 4A2 (NR4A2/NURR1) Regulates Autophagy and Chemoresistance in Pancreatic Ductal Adenocarcinoma.Cancer research communications · 2021Article
- The Paradoxical Roles of Orphan Nuclear Receptor 4A (NR4A) in Cancer.Molecular cancer research : MCR · 2021Review
- Nr4a2 Transcription Factor in Hippocampal Synaptic Plasticity, Memory and Cognitive Dysfunction: A Perspective Review.Frontiers in molecular neuroscience · 2021Review
- Assessment of NR4A Ligands That Directly Bind and Modulate the Orphan Nuclear Receptor Nurr1.Journal of medicinal chemistry · 2020Article
- Pharmacological activation of Nr4a rescues age-associated memory decline.Neurobiology of aging · 2020Article
- Nuclear receptor 4A2 (NR4A2) is a druggable target for glioblastomas.Journal of neuro-oncology · 2020Article
- Structure-dependent activation of gene expression by bis-indole and quinoline-derived activators of nuclear receptor 4A2.Chemical biology & drug design · 2019Review
- Molecular Insights into NR4A2(Nurr1): an Emerging Target for Neuroprotective Therapy Against Neuroinflammation and Neuronal Cell Death.Molecular neurobiology · 2019Review
- A novel diindolylmethane analog, 1,1-bis(3'-indolyl)-1-(p-chlorophenyl) methane, inhibits the tumor necrosis factor-induced inflammatory response in primary murine synovial fibroblasts through a Nurr1-dependent mechanism.Molecular immunology · 2018Article
- The Nurr1 Ligand,1,1-bis(3'-Indolyl)-1-(The Journal of pharmacology and experimental therapeutics · 2018Article
- Modulatory Role of Nurr1 Activation and Thrombin Inhibition in the Neuroprotective Effects of Dabigatran Etexilate in Rotenone-Induced Parkinson's Disease in Rats.Molecular neurobiology · 2018Article
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Abstract
NR4A2 (Nurr1) is an orphan nuclear receptor with no known endogenous ligands and is highly expressed in many cancer cell lines including Panc1 and Panc28 pancreatic cancer cells. Structure-dependent activation of NR4A2 by a series of 1,1-bis(3'-indolyl)-1-(aromatic)methane (C-DIM) analogs was determined in pancreatic cancer cells transfected with yeast GAL4-Nurr1 chimeras and a UASx5-luc reporter gene or constructs containing response elements that bind NR4A2. Among 23 different structural analogs, phenyl groups containing p-substituted trifluoromethyl, t-butyl, cyano, bromo, iodo and trifluoromethoxy groups were the most active compounds in transactivation assay. The p-bromophenyl analog (DIM-C-pPhBr) was used as a model for structure-activity studies among a series of ortho-, meta- and para-bromophenyl isomers and the corresponding indole 2- and N-methyl analogs. Results show that NR4A2 activation was maximal with the p-bromophenyl analog and methylation of the indole NH group abrogated activity. Moreover, using GAL4-Nurr1 (full length) or GAL-Nurr1-A/B and GAL4-Nurr1-(C-F) chimeras expressing N- and C-terminal domains of Nurr1, respectively, DIM-C-pPhBr activated all three constructs and these responses were differentially affected by kinase inhibitors. DIM-C-pPhBr also modulated expression of several Nurr1-regulated genes in pancreatic cancer cells including vasoactive intestinal peptide (VIP), and the immunohistochemical and western blot analyses indicated that DIM-C-pPhBr activates nuclear NR4A2.
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