Dissociated non-steroidal glucocorticoids: tuning out untoward effects

Area of Science:

• Endocrinology and Pharmacology
• Molecular and Cellular Biology

Background:

• Endogenous glucocorticoids (GCs), like cortisol, regulate glucose homeostasis, immune responses, and stress adaptation.
• The glucocorticoid receptor (GR) is crucial for life and a target for many approved drugs.
• Current synthetic GCs treat inflammatory conditions but cause dose-limiting side effects, partly due to metabolic roles.

Purpose of the Study:

• To review patent literature on novel non-steroidal agents targeting the glucocorticoid receptor (GR).
• To identify compounds that dissociate therapeutic immune effects from metabolic side effects.
• To explore agents retaining beneficial GR actions while minimizing adverse effects.

Main Methods:

• Comprehensive review of the existing patent literature concerning non-steroidal glucocorticoid receptor (GR) modulators.
• Analysis of chemical classes and, where known, the underlying mechanisms of action for these novel agents.

Main Results:

• Identification of various non-steroidal agents designed to selectively modulate GR activity.
• Focus on compounds aiming to separate anti-inflammatory effects from glucose-regulatory or other metabolic consequences.
• Discussion of different chemical scaffolds and their potential mechanisms for achieving dissociated effects.

Conclusions:

• There is significant research and patent activity focused on developing non-steroidal GR modulators.
• These novel agents hold promise for improved therapies with reduced side effect profiles compared to traditional GCs.
• Further investigation into the chemical classes and mechanisms is crucial for clinical translation.