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Trends Pharmacol Sci. 2016 Jan;37(1):4-16. doi: 10.1016/j.tips.2015.09.002. Epub 2015 Oct 22.

Activation of the Glucocorticoid Receptor in Acute Inflammation: the SEDIGRAM Concept.

Author information

1
Receptor Research Laboratories, Nuclear Receptor Lab (NRL), VIB Department of Medical Protein Research, Ghent University, Albert Baertsoenkaai 3, B-9000 Gent, Belgium.
2
Laboratory of Experimental Cancer Research (LECR), Department of Radiation Oncology and Experimental Cancer Research, Ghent University, De Pintelaan 185, 1P7, B-9000 Gent, Belgium.
3
Laboratory of Protein Chemistry, Proteomics and Epigenetic Signaling, Department of Biomedical Sciences, University of Antwerp (UA), Campus Drie Eiken, Universiteitsplein 1, D.T.135, B-2610 Wilrijk, Belgium.
4
Inflammation Research Center, VIB, Ghent, Belgium and Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, B-9052 Gent, Belgium. Electronic address: Claude.Libert@irc.vib-ugent.be.

Abstract

Since the 1950s, glucocorticoids (GCs) have been a mainstay therapy for acute and chronic inflammatory disorders, although adverse effects limit their chronic use. Following the notion that the anti-inflammatory therapeutic and metabolic endocrine adverse effects of GCs may be based on different glucocorticoid receptor (GR)-dependent mechanisms, subsequent attempts to separate these mechanisms by trying to develop selective GR agonists and modulators (SEGRAMs) with an improved therapeutic benefit have yielded only a few molecules effective in clinical use. Recent new insights into the pro- and anti-inflammatory activities of GR support a more sophisticated drug discovery model. Here, we suggest that the way forward may include a need to redefine the pharmacological SEGRAM concept into selective monomerizing GR agonists and modulators (SEMOGRAMs) and selective dimerizing GR agonists or modulators (SEDIGRAMs) for selective therapeutic applications against chronic or acute inflammatory disorders, respectively.

PMID:
26603477
DOI:
10.1016/j.tips.2015.09.002
[Indexed for MEDLINE]

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