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Glucocorticoid receptor modulators.

Onno C Meijer1, Lisa L Koorneef1, Jan Kroon1

  • 1Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.

Annales D'Endocrinologie
|May 8, 2018
PubMed
Summary

Selective glucocorticoid receptor modulators offer a new approach to medicine. These compounds target the glucocorticoid receptor, aiming for therapeutic benefits while minimizing side effects associated with cortisol signaling.

Keywords:
BrainCancerCerveauCo-activateursCoactivatorsCortisolDiseaseEffets secondairesGlucocorticoidsGlucocorticoïdesMaladieMetabolismMétabolismeSide effectsStress

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Area of Science:

  • Endocrinology
  • Molecular Pharmacology
  • Systems Biology

Background:

  • Cortisol is a key hormone regulating circadian rhythms and stress response.
  • The glucocorticoid receptor (GR) mediates cortisol's effects and is a target for synthetic drugs.
  • Current GR agonists/antagonists have broad effects, leading to side effects.

Purpose of the Study:

  • To explore the mechanisms of selective glucocorticoid receptor modulators (SGRMs).
  • To discuss the therapeutic potential of SGRMs in various diseases.
  • To highlight how SGRMs offer a way to activate specific GR signaling pathways.

Main Methods:

  • Review of existing literature on glucocorticoid receptor signaling.
  • Analysis of the molecular mechanisms underlying selective receptor modulation.
  • Discussion of preclinical and clinical data on SGRMs.

Main Results:

  • SGRMs induce specific GR conformations, leading to selective downstream signaling.
  • This selectivity allows for targeted therapeutic effects.
  • Potential for SGRMs to treat diseases in multiple organ systems is demonstrated.

Conclusions:

  • Selective glucocorticoid receptor modulation represents a promising therapeutic strategy.
  • SGRMs can decouple beneficial effects from unwanted side effects of traditional glucocorticoids.
  • Further research into SGRMs could lead to novel treatments for a range of conditions.