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Antitumor activity of a PPARδ antagonist

Vascular Biology Center, Division of Hematology Oncology and Transplantation, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Cancer biology & therapy (Impact Factor: 3.07). 08/2009; 8(13):1262-4. DOI: 10.4161/cbt.8.13.9061
Source: PubMed

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Commentary to: Regulation of drug resistance by human pregnane X receptor in breast cancer Yakun Chen, Yong Tang, Shuqing Chen, Daotai NieEdit authors

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    ABSTRACT: A broad range of chemical structures modulate the inductive and repressive transcriptional regulation of the peroxisome proliferator-activated receptor [small beta]/[small delta] (PPAR[small beta]/[small delta]). In order to shed light on mechanistic differences in the modes of action of three classes of the reported PPAR[small beta]/[small delta] antagonists, an investigation into their in vitro biological and chemical reactivities, with particular focus on covalent reactivity, was undertaken. The results reported here, substantiate the covalent modification of Cys249 as a part of the mode of action of the 5-trifluoromethyl-2-sulfonylpyridine class of antagonists. In contrast, GSK0660 does not appear to be a covalently binding antagonistic ligand. Additionally, we demonstrate the electrophilic nature of the recently published antagonist DG172 towards thiolates, although a covalent adduct with PPAR[small beta]/[small delta] is not detected in our experiments.
    Full-text · Article · Aug 2015 · RSC Advances