JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
REVIEW
Add like
Add dislike
Add to saved papers

Advances in drug design with RXR modulators.

INTRODUCTION: Retinoid X receptors (subtypes RXRα or NR2B1, RXRβ or NR2B2 and RXRγ or NR2B3, which originate from three distinct genes) are promiscuous partners with heterodimeric associations to other members of the Nuclear Receptor (NR) superfamily. Some of the heterodimers are "permissive" and transcriptionally active in the presence of either an RXR ligand ("rexinoid") or a NR partner ligand, whereas others are "non-permissive" and unresponsive to rexinoids alone. In rodent models, rexinoids and partner agonists (mainly PPARγ, LXR, FXR) produce beneficial effects on insulin sensitization, diabetes and obesity, but secondary effects have also been noted, such as a raise in tryglyceride levels, supression of the thyroid hormone axis and induction of hepatomegaly.

AREAS COVERED: The authors review recent advances in rexinoid design, including further optimization of known scaffolds, and the discovery of novel RXR modulators by virtual ligand screening or from bioactive natural products. The understanding of rexinoid functions in permissive and non-permissive heterodimers is firmly based on structural knowledge. By strenghtening or disrupting the interaction surface with coregulators rexinoids exert agonist or (partial) antagonist activities. The activity state of the heterodimer can also be fine-tuned by the cellular context and the nature of coregulators.

EXPERT OPINION: The synthetic chemistry toolbox has provided a panel of agonists, partial (ant)agonists and/or heterodimer-selective rexinoids starting from existing, naturally occurring or serendipitously discovered scaffolds. These compounds have an unexplored therapeutic potential that might overcome some of the current limitations of rexinoids in therapy, such as hypertriglyceridemia.

Full text links

We have located links that may give you full text access.
Can't access the paper?
Try logging in through your university/institutional subscription. For a smoother one-click institutional access experience, please use our mobile app.

For the best experience, use the Read mobile app

Mobile app image

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

By using this service, you agree to our terms of use and privacy policy.

Your Privacy Choices Toggle icon

You can now claim free CME credits for this literature searchClaim now

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app