Vitamin A (retinol) and its metabolites play many physiological roles including cell differentiation, cell proliferation, energy homeostasis, circadian rhythm and immune response. Vitamin A and its metabolites are known to act through retinoid acid receptors (RARs), retinoid-related orphan receptors (RORs) and retinoid x receptors (RXRs). These receptors are also important drug targets, although the specificity of many retinoid-like compounds for the retinoid receptors has not been carefully explored due to the lack of robust and selective assays. In the present work we examined 25 retinoid-like compounds for their ability to regulate RAR-alpha, -beta, -gamma, RXR-alpha, -beta, -gamma, and ROR-alpha, -beta, -gamma. Compounds were tested for agonistic as well as antagonistic activities towards these receptors. Additionally cytotoxicity analyses were performed to confirm true antagonistic activity. Many of these compounds show a broad range of receptor activity, while others show moderate selectivity. Only a few of these test compounds show significant antagonist activity to these retinoid receptors, illustrating the need to screen more broadly for drug candidates with improved specificity in inhibiting the human RXRs, RARs and RORs, as well as selectivity in targeting one receptor sub-type (a, b, or g) over the others.

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Date of publication: 10 March 2013; Poster

Author information: Prajakta Albrecht (1); Koji Toyokawa (1); Ewa Maddox (1); Palmer Cramer (1); Jack Vanden Heuvel (1,2); & Bruce Sherf (1)

(1) INDIGO Biosciences, State College, PA 16801, United States
(2) Department of Vetrinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, United States


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