Retinoid X Receptor Assays

Overview of Retinoid X Receptors (RXR)

The RXR belongs to the nuclear receptor family and plays an essential role in miscellaneous aspects of animal life. RXR forms heterodimers with diverse other nuclear receptors, such as the liver X receptor (LXR) as well as the vitamin D receptor (VDR), placing it at the crossroads of numerous biological pathways. RXR is now composed of three isoforms, RXRα, RXRβ, and RXRγ, encoded by diverse genes and giving rise to many alternatively spliced variants.

Fig.1 Complex roles of RXRs in macrophages. Fig.1. Complex roles of RXRs in macrophages. (Rőszer, 2013)

Functions of RXR

RXRs have different tissue distributions. RXRα is present in the liver, lung, kidney, muscle, epidermis, and gut. RXRβ can be found in almost every tissue while RXRγ is restricted to muscles, the pituitary gland, and certain parts of the brain. RXR is closely related to embryonic development. Furthermore, RXRs are involved in the regulation of multiple physiological and metabolic activities, such as cell differentiation, immune responses, and lipid and glucose metabolism.

Pathways of RXRs

RXRs can bind DNA in the form of homodimers and homotetramers, suggesting that RXRs may control their own signaling pathways, making the study of the RXR pathway more challenging.

Receptor	Gene	Mechanism	Agonists	Antagonists
RXRα	RXRA	RXRa can interact with the Akt and activate the PI3K/Akt pathway.	CD 3254 Bexarotene DC 271 Docosahexaenoic acid LG 100268 Retinoic acid SR 11237 Am580	HX 531 PA 452 UVI 3003 LG100754 AGN195393 LG101506
RXRβ	RXRB	Many genes are involved in RXRβ signaling during remyelination.
RXRγ	RXRG	The RXRγ signaling pathway can regulate a variety of life activities.

Published Data

Paper Title	Retinoid X Receptor Antagonists
Journal	International journal of molecular sciences
Published	2018
Abstract	RXRs are pivotal receptors that are available as homodimers or as heterodimers with a variety of other receptors. RXR heterodimers that can be activated by RXR agonists alone are referred to as permissive heterodimers. 9-cis-Retinoic acid is a potent RXR natural agonist. In addition, synthetic agonists of RXR are used in the therapy of cutaneous T-cell lymphoma (CTCL). However, on the other hand, no RXR antagonists have yet entered clinical use, even though anti-type 2 diabetes and anti-allergic activities have been found in animal models. At present, RXR antagonists are mainly used as analytical tools for RXR functional studies. This article provides a brief introduction to the structure, functions as well as target genes of RXR, followed by an explanation of currently available RXR antagonists, their structural classification, and evaluation.
Result	RXR antagonists have gradually become the focus of research due to their therapeutic effects, such as hypoglycemic effects in diabetes models and antitumor effects via tRXRα. However, in addition to being poorly absorbed, some of the currently available RXR antagonists activate heterodimers, and thus, therapeutic efficacy relies on high-dose oral administration. Therefore, the discovery of new RXR antagonists to overcome these problems remains urgent, and these compounds will be potential drug candidates and key tools in the biological study of nuclear receptor action. Fig.2. Chemical structures of RXR agonists and RXR antagonists having a long-chain alkoxy group. (Watanabe, 2018)

References

Rőszer, T.; et al. Retinoid X receptors in macrophage biology. Trends in Endocrinology & Metabolism. 2013; 24(9): 460-468.
Watanabe, M.; Kakuta, H. Retinoid X Receptor Antagonists. International journal of molecular sciences. 2018; 19(8): 2354.

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