In order to determine the feasibility of utilizing novel rexinoids for chemotherapeutics and as potential treatments for neurological conditions, we undertook an assessment of the side effect profile of select rexinoid X receptor (RXR) analogs that we reported previously. We assessed pharmacokinetic profiles, lipid and thyroid-stimulating hormone (TSH) levels in rats, and cell culture activity of rexinoids in sterol regulatory element-binding protein (SREBP) induction and thyroid hormone inhibition assays. We also performed RNA sequencing of the brain tissues of rats that had been dosed with the compounds. We show here for the first time that potent rexinoid activity can be uncoupled from drastic lipid changes and thyroid axis variations, and we propose that rexinoids can be developed with improved side effect profiles than the parent compound, bexarotene (1).
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- Analysis of Differential Secondary Effects of Novel Rexinoids: Select Rexinoid X Receptor Ligands Demonstrate Differentiated Side Effect Profiles
- Marshall, Pamela (Author)
- Jurutka, Peter (Author)
- Wagner, Carl (Author)
- van der Vaart, Arjan (Author)
- Kaneko, Ichiro (Author)
- Chavez, Pedro I. (Author)
- Ma, Ning (Author)
- Bhogal, Jaskaran (Author)
- Shahani, Pritika (Author)
- Swierski, Johnathon (Author)
- MacNeill, Mairi (Author)
- New College of Interdisciplinary Arts and Sciences (Contributor)
- Digital object identifier: 10.1002/prp2.122
- Identifier TypeInternational standard serial numberIdentifier Value2052-1707
- The final version of this article, as published in Pharmacology Research & Perspectives, can be viewed online at: http://onlinelibrary.wiley.com/doi/10.1002/prp2.122/abstract?
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Marshall, P. A., Jurutka, P. W., Wagner, C. E., Vaart, A. V., Kaneko, I., Chavez, P. I., . . . Macneill, M. (2015). Analysis of differential secondary effects of novel rexinoids: select rexinoid X receptor ligands demonstrate differentiated side effect profiles. Pharmacology Research & Perspectives, 3(2). doi:10.1002/prp2.122