Analysis of differential secondary effects of novel rexinoids: Select rexinoid X receptor ligands demonstrate differentiated side effect profiles

Pamela Marshall, Peter Jurutka, Carl Wagner, Arjan van der Vaart, Ichiro Kaneko, Pedro I. Chavez, Ning Ma, Jaskaran S. Bhogal, Pritika Shahani, Johnathon C. Swierski, Mairi Macneill

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

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).

Original languageEnglish (US)
Pages (from-to)1-19
Number of pages19
JournalPharmacology Research and Perspectives
Volume3
Issue number2
DOIs
StatePublished - Mar 1 2015

Keywords

  • Bexarotene
  • Lipids
  • Rexinoids
  • RXR
  • Thyroid

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Neurology

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