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Immunopharmacology and Inflammation pp 283–305Cite as

Strategies and Compounds to Circumvent Glucocorticoid-Induced Side Effects

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Abstract

Glucocorticoids (GCs) are used in the clinic for the treatment of inflammatory diseases and particular cancers. Although they are highly efficient in combating inflammation, their use is limited. This is caused by quality-of-life-threatening side effects, e.g. osteoporosis and metabolic imbalances. Contemporary efforts still focus on the development and characterization of novel (non-)steroidal ligands that can separate the beneficial anti-inflammatory effects from the plethora of adverse effects. However, early-day views of how GCs mechanistically work appeared too simplistic to cover the complexity and pleiotropicity of glucocorticoid receptor (GR)-mediated therapeutic actions. In this chapter, we will zoom in on the rationale of selective GR agonist design and recent advances in the field. We will discuss in detail how exemplary novel GR-agonists are able or expected to circumvent specific GC-induced side effects. Today, although novel selective GR-drugs have demonstrated therapeutic benefit in pre-clinical and clinical trials, reaching the pharmacy market remains an insurmountable hurdle. This calls for stepping up knowledge-gathering efforts alongside a serious rethinking of strategies within the field.

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Authors and Affiliations

  1. Receptor Research Laboratories, Department of Biochemistry, Ghent University, Ghent, Belgium

    Astrid Luypaert, Jan Tavernier & Karolien De Bosscher

  2. VIB-UGent Center for Medical Biotechnology, Ghent, Belgium

    Astrid Luypaert, Jan Tavernier & Karolien De Bosscher

  3. PPES Lab Protein Science, Proteomics and Epigenetic Signaling, Department Biomedical Sciences, University of Antwerp, Wilrijk, Belgium

    Wim Vanden Berghe

  4. Inflammation Research Center, VIB, Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium

    Claude Libert

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  1. Astrid Luypaert
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  2. Wim Vanden Berghe
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  3. Jan Tavernier
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  4. Claude Libert
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  5. Karolien De Bosscher
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Correspondence to Karolien De Bosscher .

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Editors and Affiliations

  1. Department of Medicine, Section of Pharmacology, University of Perugia, Perugia, Italy

    Carlo Riccardi

  2. Pharmacology and Experimental Therapeutics Unit, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel

    Francesca Levi-Schaffer

  3. Department of Pharmacology, Medical School, National and Kapodistrian University of Athens, Athens, Greece

    Ekaterini Tiligada

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Luypaert, A., Vanden Berghe, W., Tavernier, J., Libert, C., De Bosscher, K. (2018). Strategies and Compounds to Circumvent Glucocorticoid-Induced Side Effects. In: Riccardi, C., Levi-Schaffer, F., Tiligada, E. (eds) Immunopharmacology and Inflammation. Springer, Cham. https://doi.org/10.1007/978-3-319-77658-3_13

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