Open AccessAnalysis of differential secondary effects of novel rexinoids: select rexinoid X receptor ligands demonstrate differentiated side effect profiles
Author(s) -
Marshall Pamela A.,
Jurutka Peter W.,
Wagner Carl E.,
Vaart Arjan,
Kaneko Ichiro,
Chavez Pedro I.,
Ma Ning,
Bhogal Jaskaran S.,
Shahani Pritika,
Swierski Johnathon C.,
MacNeill Mairi
Publication year - 2015
Publication title -
pharmacology research and perspectives
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.975
H-Index - 27
ISSN - 2052-1707
DOI - 10.1002/prp2.122
Subject(s) - bexarotene , thyroid , retinoid x receptor , hormone , pharmacology , side effect (computer science) , receptor , sterol regulatory element binding protein , chemistry , sterol , medicine , cholesterol , endocrinology , biochemistry , nuclear receptor , transcription factor , computer science , gene , programming language
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 ).