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Retinoid and Rexinoid Signaling pp 51–72Cite as

Ligand Design for Modulation of RXR Functions

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 2019))

Abstract

Retinoid X receptors (RXRs) are promiscuous partners of heterodimeric associations with other members of the Nuclear Receptor (NR) superfamily. RXR ligands (“rexinoids”) either transcriptionally activate the “permissive” subclass of heterodimers or synergize with partner ligands in the “nonpermissive” subclass of heterodimers. The rationale for rexinoid design with a wide structural diversity going from the structures of existing complexes with RXR determined by X-Ray, to natural products and other ligands discovered by high-throughput screening (HTS), mere serendipity, and rationally designed based on Molecular Modeling, will be described. Included is the new generation of ligands that modulate the structure of specific receptor surfaces that serve to communicate with other regulators. The panel of the known RXR agonists, partial (ant)agonists, and/or heterodimer-selective rexinoids require the exploration of their therapeutic potential in order to overcome some of the current limitations of rexinoids in therapy.

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Acknowledgments

This work was supported by grants from the Spanish MINECO (SAF2016-77620-R-FEDER), Xunta de Galicia (Consolidación GRC 2017/61 from DXPCTSUG; ED-431G/02-FEDER “Unha maneira de facer Europa” to CINBIO, a Galician research center 2016-2019); Juan de la Cierva Contract to J. A. S.).

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  1. Departamento de Química Orgánica, Facultade de Química, CINBIO and IBIV, Universidade de Vigo, Vigo, Spain

    Claudio Martínez, José A. Souto & Angel R. de Lera

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  1. Claudio Martínez
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  2. José A. Souto
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  3. Angel R. de Lera
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Correspondence to Angel R. de Lera .

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  1. Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, SC, USA

    Swapan K. Ray

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Martínez, C., Souto, J.A., de Lera, A.R. (2019). Ligand Design for Modulation of RXR Functions. In: Ray, S. (eds) Retinoid and Rexinoid Signaling . Methods in Molecular Biology, vol 2019. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9585-1_4

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