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Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

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Nuclear Receptor Function through Genomics: Lessons from the Glucocorticoid Receptor.

Daniel M Cohen¹, David J Steger¹

¹Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, and The Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.

Trends in Endocrinology and Metabolism: TEM

|May 13, 2017

Summary

Researchers are developing new glucocorticoid receptor (GR) drugs to reduce side effects. Genomic studies are helping to understand how GR controls gene expression for better anti-inflammatory therapies.

Keywords:

cistromics functional genomics glucocorticoid receptor nuclear receptor transcription

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Area of Science:

Molecular Biology
Genomics
Pharmacology

Background:

The glucocorticoid receptor (GR) is a key target for anti-inflammatory and immunosuppressive drugs.
Current GR modulators can cause metabolic side effects, limiting their therapeutic use.
Understanding GR's complex transcriptional regulation is crucial for developing safer drugs.

Purpose of the Study:

To review recent genomic studies on GR transcriptional regulation.
To discuss how these findings can inform the development of novel GR ligands.
To highlight the goal of creating GR modulators with reduced metabolic liabilities.

Main Methods:

Review of recent genomic studies.
Analysis of nuclear receptor-mediated transcription models.
Discussion of structure-activity relationships for GR ligands.

Main Results:

Genomic studies have provided new insights into GR's tissue-specific gene regulation.
These insights challenge and refine existing models of GR action.
The findings support the potential for developing selective GR modulators.

Conclusions:

Recent genomic advances offer a deeper understanding of GR function.
This knowledge facilitates the design of improved GR-targeted therapeutics.
The development of GR ligands with enhanced safety profiles is a key future direction.