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Updated: Jun 27, 2026

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
Published on: November 15, 2013
Replacing alkyl sulfonamide with aromatic sulfonamide in sulfonamide-type RXR agonists favors switch towards
Ken-ichi Morishita1, Nobumasa Yakushiji, Fuminori Ohsawa
1Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 1-1-1, Tsushima-Naka, Okayama 700-8530, Japan.
Abstract:
Retinoid X receptor (RXR) ligands are attractive candidates for clinical application because of their activity against tamoxifen-resistant breast cancer, taxol-resistant lung cancer, metabolic syndrome, and allergy. Though several RXR ligands, especially RXR antagonists, have been reported, the rational molecular design of such compounds is not well advanced. 4-[N-Methanesulfonyl-N-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)amino]nicotinic acid (5a) is a moderately RXRalpha-preferential agonist, and we examined the feasibility of replacing the methyl group on the sulfonamide with a longer alkyl chain or an aromatic ring as an approach to produce new RXR antagonists. Several of the resulting benzenesulfonanilide-type compounds showed RXR antagonist activity. This design strategy should be a useful approach for addressing the lack of structure diversity of RXR antagonists.
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