title: Analysis of differential secondary effects of novel rexinoids: select rexinoid X receptor ligands demonstrate differentiated side effect profiles.
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).
authors.affiliation: School of Mathematical and Natural Sciences, New College of Interdisciplinary Arts and Sciences, Arizona State University 4701 W Thunderbird Rd, Glendale, Arizona, 85306.
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Marshall
authors.affiliation: School of Mathematical and Natural Sciences, New College of Interdisciplinary Arts and Sciences, Arizona State University 4701 W Thunderbird Rd, Glendale, Arizona, 85306.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Jurutka
authors.affiliation: School of Mathematical and Natural Sciences, New College of Interdisciplinary Arts and Sciences, Arizona State University 4701 W Thunderbird Rd, Glendale, Arizona, 85306.
authors.forename: Carl E
authors.initials: CE
authors.lastname: Wagner
authors.affiliation: Department of Chemistry, University of South Florida 4202 E Fowler Ave CHE 205, Tampa, Florida, 33620.
authors.forename: Arjan
authors.initials: A
authors.lastname: van der Vaart
authors.affiliation: School of Mathematical and Natural Sciences, New College of Interdisciplinary Arts and Sciences, Arizona State University 4701 W Thunderbird Rd, Glendale, Arizona, 85306.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kaneko
authors.affiliation: Biomedical Sciences Program, Midwestern University 19555 N 59th Ave., Glendale, Arizona, 86308.
authors.forename: Pedro I
authors.initials: PI
authors.lastname: Chavez
authors.affiliation: Department of Chemistry, University of South Florida 4202 E Fowler Ave CHE 205, Tampa, Florida, 33620.
authors.forename: Ning
authors.initials: N
authors.lastname: Ma
authors.affiliation: School of Mathematical and Natural Sciences, New College of Interdisciplinary Arts and Sciences, Arizona State University 4701 W Thunderbird Rd, Glendale, Arizona, 85306.
authors.forename: Jaskaran S
authors.initials: JS
authors.lastname: Bhogal
authors.affiliation: School of Mathematical and Natural Sciences, New College of Interdisciplinary Arts and Sciences, Arizona State University 4701 W Thunderbird Rd, Glendale, Arizona, 85306.
authors.forename: Pritika
authors.initials: P
authors.lastname: Shahani
authors.affiliation: School of Mathematical and Natural Sciences, New College of Interdisciplinary Arts and Sciences, Arizona State University 4701 W Thunderbird Rd, Glendale, Arizona, 85306.
authors.forename: Johnathon C
authors.initials: JC
authors.lastname: Swierski
authors.affiliation: School of Mathematical and Natural Sciences, New College of Interdisciplinary Arts and Sciences, Arizona State University 4701 W Thunderbird Rd, Glendale, Arizona, 85306.
authors.forename: Mairi
authors.initials: M
authors.lastname: MacNeill
keywords: Bexarotene; RXR; lipids; rexinoids; thyroid