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Updated: May 18, 2026

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
Published on: February 20, 2018
Advances in drug design with RXR modulators
1Departamento de Química Orgánica, Facultad de Química and Centro de Investigaciones Biomédicas (CINBIO), Universidade de Vigo, Vigo, Spain.
Synthetic rexinoids offer new therapeutic potential for metabolic diseases by modulating Retinoid X Receptor (RXR) activity. Novel compounds may overcome limitations like hypertriglyceridemia, advancing RXR-targeted therapies.
Area of Science:
- Nuclear Receptor Superfamily
- Retinoid X Receptors (RXRs)
- Heterodimerization
Background:
- RXRs form heterodimers with other Nuclear Receptors, exhibiting permissive or non-permissive transcriptional activity.
- Rexinoids and partner agonists show promise in rodent models for insulin sensitization, diabetes, and obesity.
- Known side effects include hypertriglyceridemia, thyroid axis suppression, and hepatomegaly.
Purpose of the Study:
- To review advances in rexinoid design and discovery.
- To explore the structural basis of rexinoid function in RXR heterodimers.
- To highlight the therapeutic potential of novel rexinoids.
Main Methods:
- Review of recent literature on rexinoid design and discovery.
- Analysis of structural data for rexinoid-heterodimer interactions.
- Discussion of synthetic chemistry approaches for rexinoid development.
Main Results:
- Optimization of known scaffolds and discovery of novel RXR modulators.
- Understanding rexinoid mechanisms through structural insights into permissive/non-permissive heterodimers.
- Identification of compounds with agonist, partial (ant)agonist, or heterodimer-selective activities.
Conclusions:
- Synthetic chemistry has yielded diverse rexinoids (agonists, antagonists, selective modulators).
- These compounds possess unexplored therapeutic potential.
- Novel rexinoids may address limitations of current therapies, such as hypertriglyceridemia.
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