ArticleThe Journal of biological chemistry2010
Abrogation of glucocorticoid receptor dimerization correlates with dissociated glucocorticoid behavior of compound a.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
42 citing papers in PubMed, 76 citations in OpenAlex.
- Glucocorticoids, their uses, sexual dimorphisms, and diseases: new concepts, mechanisms, and discoveries.Physiological reviews · 2024Review
- Phosphodiesterase 5 inhibitor mirodenafil ameliorates Alzheimer-like pathology and symptoms by multimodal actions.Alzheimer's research & therapy · 2022Article
- Glutamine synthetase regulation by dexamethasone, RU486, and compound A in astrocytes derived from aged mouse cerebral hemispheres is mediated via glucocorticoid receptor.Molecular and cellular biochemistry · 2021Article
- Review
- Glucocorticoid Priming of Nonviral Gene Delivery to hMSCs Increases Transfection by Reducing Induced Stresses.Molecular therapy. Methods & clinical development · 2020Article
- A Novel Approach to Safer Glucocorticoid Receptor-Targeted Anti-lymphoma Therapy via REDD1 (Regulated in Development and DNA Damage 1) Inhibition.Molecular cancer therapeutics · 2020Article
- Anti-Proliferative Effects of Compound A and Its Effect in Combination with Cisplatin in Cholangiocarcinoma Cells.Asian Pacific journal of cancer prevention : APJCP · 2020Article
- Glucocorticoid-Induced Ocular Hypertension: Origins and New Approaches to Minimize.Expert review of ophthalmology · 2020Article
- Glucocorticoid Receptor Transactivation Is Required for Glucocorticoid-Induced Ocular Hypertension and Glaucoma.Investigative ophthalmology & visual science · 2019Article
- GR Dimerization and the Impact of GR Dimerization on GR Protein Stability and Half-Life.Frontiers in immunology · 2019Review
- Disease- and treatment-associated acquired glucocorticoid resistance.Endocrine connections · 2018Review
- Novel role for receptor dimerization in post-translational processing and turnover of the GRα.Scientific reports · 2018Article
- A screening assay for Selective Dimerizing Glucocorticoid Receptor Agonists and Modulators (SEDIGRAM) that are effective against acute inflammation.Scientific reports · 2018Article
- Effect of combining glucocorticoids with Compound A on glucocorticoid receptor responsiveness in lymphoid malignancies.PloS one · 2018Article
- Compound A influences gene regulation of the Dexamethasone-activated glucocorticoid receptor by alternative cofactor recruitment.Scientific reports · 2017Article
- A Quantitative Study of Internal and External Interactions of Homodimeric Glucocorticoid Receptor Using Fluorescence Cross-Correlation Spectroscopy in a Live Cell.Scientific reports · 2017Article
- More than meets the dimer: What is the quaternary structure of the glucocorticoid receptor?Transcription · 2017Article
- GR-independent down-modulation on GM-CSF bone marrow-derived dendritic cells by the selective glucocorticoid receptor modulator Compound A.Scientific reports · 2016Article
- Glucocorticoid therapy and ocular hypertension.European journal of pharmacology · 2016Review
- VBP15, a novel dissociative steroid compound, reduces NFκB-induced expression of inflammatory cytokines in vitro and symptoms of murine trinitrobenzene sulfonic acid-induced colitis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2016Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Compound A (CpdA), a dissociated glucocorticoid receptor modulator, decreases corticosteroid-binding globulin (CBG), adrenocorticotropic hormone (ACTH), and luteneinizing hormone levels in rats. Whether this is due to transcriptional regulation by CpdA is not known. Using promoter reporter assays we show that CpdA, like dexamethasone (Dex), directly transrepresses these genes. Results using a rat Cbg proximal-promoter reporter construct in BWTG3 and HepG2 cell lines support a glucocorticoid receptor (GR)-dependent transrepression mechanism for CpdA. However, CpdA, unlike Dex, does not result in transactivation via glucocorticoid-responsive elements within a promoter reporter construct even when GR is co-transfected. The inability of CpdA to result in transactivation via glucocorticoid-responsive elements is confirmed on the endogenous tyrosine aminotransferase gene, whereas transrepression ability is confirmed on the endogenous CBG gene. Consistent with a role for CpdA in modulating GR activity, whole cell binding assays revealed that CpdA binds reversibly to the GR, but with lower affinity than Dex, and influences association of [(3)H]Dex, but has no effect on dissociation. In addition, like Dex, CpdA causes nuclear translocation of the GR, albeit to a lesser degree. Several lines of evidence, including fluorescence resonance energy transfer, co-immunoprecipitation, and nuclear immunofluorescence studies of nuclear localization-deficient GR show that CpdA, unlike Dex, does not elicit ligand-induced GR dimerization. Comparison of the behavior of CpdA in the presence of wild type GR to that of Dex with a dimerization-deficient GR mutant (GR(dim)) strongly supports the conclusion that loss of dimerization is responsible for the dissociated behavior of CpdA.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.