ArticleScientific reports2018
A screening assay for Selective Dimerizing Glucocorticoid Receptor Agonists and Modulators (SEDIGRAM) that are effective against acute inflammation.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 22 citations in OpenAlex.
- Selective Glucocorticoid Receptor Modulators (SEGRAMs): Can They Improve the Therapeutic Index of Steroid Therapy?Medical science monitor : international medical journal of experimental and clinical research · 2026Review
- Skin Anti-Inflammatory Potential with Reduced Side Effects of Novel Glucocorticoid Receptor Agonists.International journal of molecular sciences · 2023Article
- Dimerization of the Glucocorticoid Receptor and Its Importance in (Patho)physiology: A Primer.Cells · 2022Review
- The long winding road to the safer glucocorticoid receptor (GR) targeting therapies.Oncotarget · 2022Review
- Comparative efficacy of glucocorticoid receptor agonists on Th2 cell function and attenuation by progesterone.BMC immunology · 2020Article
- Nuclear Receptors Regulate Intestinal Inflammation in the Context of IBD.Frontiers in immunology · 2019Review
- Fighting the Fire: Mechanisms of Inflammatory Gene Regulation by the Glucocorticoid Receptor.Frontiers in immunology · 2019Review
- Potential Dissociative Glucocorticoid Receptor Activity for Protopanaxadiol and Protopanaxatriol.International journal of molecular sciences · 2018Article
- Glucocorticoid receptor Thr524 phosphorylation by MINK1 induces interactions with 14-3-3 protein regulators.The Journal of biological chemistryArticle
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It has been suggested that glucocorticoid receptor (GR) agonists that promote GR homodimerization more than standard glucocorticoids such as Dexamethasone could be more effective anti-inflammatory molecules against acute and life-threatening inflammatory conditions. To test this hypothesis, we set up a screening pipeline aimed at discovering such Selective Dimerizing GR Agonists and Modulators (SEDIGRAM). The pipeline consists of a reporter gene assay based on a palindromic glucocorticoid responsive element (GRE). This assay represents GR dimerization in human A549 lung epithelial cells. In the pipeline, this is followed by analysis of endogenous GRE-driven gene expression, a FRET assay confirming dimerization, and monitoring of in vitro and in vivo anti-inflammatory activity. In a proof of principle experiment, starting from seven candidate compounds, we identified two potentially interesting compounds (Cortivazol and AZD2906) that confer strong protection in a mouse model of aggressive TNF-induced lethal inflammation. A screening pipeline for SEDIGRAM may assist the search for compounds that promote GR dimerization and limit overwhelming acute inflammatory responses.
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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.