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Strategies and Compounds to Circumvent Glucocorticoid-Induced Side Effects

  • Astrid Luypaert
  • Wim Vanden Berghe
  • Jan Tavernier
  • Claude Libert
  • Karolien De Bosscher
Chapter

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.

Keywords

Glucocorticoid receptor Selective GR agonists and modulators Dissociating ligands Glucocorticoid-induced side effects 

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Astrid Luypaert
    • 1
    • 2
  • Wim Vanden Berghe
    • 3
  • Jan Tavernier
    • 1
    • 2
  • Claude Libert
    • 4
  • Karolien De Bosscher
    • 1
    • 2
  1. 1.Receptor Research Laboratories, Department of BiochemistryGhent UniversityGhentBelgium
  2. 2.VIB-UGent Center for Medical BiotechnologyGhentBelgium
  3. 3.PPES Lab Protein Science, Proteomics and Epigenetic Signaling, Department Biomedical SciencesUniversity of AntwerpWilrijkBelgium
  4. 4.Inflammation Research Center, VIB, Department of Biomedical Molecular Biology, Ghent UniversityGhentBelgium

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