Identification of Bexarotene as a PPAR γ Antagonist with HDX
Joint Authors
Marciano, David P.
Kuruvilla, Dana S.
Pascal, Bruce D.
Griffin, Patrick R.
Source
Issue
Vol. 2015, Issue 2015 (31 Dec. 2015), pp.1-6, 6 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-09-15
Country of Publication
Egypt
No. of Pages
6
Main Subjects
Abstract EN
The retinoid x receptors (RXRs) are the pharmacological target of Bexarotene, an antineoplastic agent indicated for the treatment of cutaneous T cell lymphoma (CTCL).
The RXRs form heterodimers with several nuclear receptors (NRs), including peroxisome proliferator-activated receptor gamma (PPARγ), to regulate target gene expression through cooperative recruitment of transcriptional machinery.
Here we have applied hydrogen/deuterium exchange (HDX) mass spectrometry to characterize the effects of Bexarotene on the conformational plasticity of the intact RXRα:PPARγ heterodimer.
Interestingly, addition of Bexarotene to PPARγ in the absence of RXRα induced protection from solvent exchange, suggesting direct receptor binding.
This observation was confirmed using a competitive binding assay.
Furthermore, Bexarotene functioned as a PPARγ antagonist able to alter rosiglitazone induced transactivation in a cell based promoter:reporter transactivation assay.
Together these results highlight the complex polypharmacology of lipophilic NR targeted small molecules and the utility of HDX for identifying and characterizing these interactions.
American Psychological Association (APA)
Marciano, David P.& Kuruvilla, Dana S.& Pascal, Bruce D.& Griffin, Patrick R.. 2015. Identification of Bexarotene as a PPAR γ Antagonist with HDX. PPAR Research،Vol. 2015, no. 2015, pp.1-6.
https://search.emarefa.net/detail/BIM-1075956
Modern Language Association (MLA)
Marciano, David P.…[et al.]. Identification of Bexarotene as a PPAR γ Antagonist with HDX. PPAR Research No. 2015 (2015), pp.1-6.
https://search.emarefa.net/detail/BIM-1075956
American Medical Association (AMA)
Marciano, David P.& Kuruvilla, Dana S.& Pascal, Bruce D.& Griffin, Patrick R.. Identification of Bexarotene as a PPAR γ Antagonist with HDX. PPAR Research. 2015. Vol. 2015, no. 2015, pp.1-6.
https://search.emarefa.net/detail/BIM-1075956
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1075956