Styrylphenylphthalimides as Novel Transrepression-Selective Liver X Receptor (LXR) Modulators

Sayaka Nomura, Kaori Endo-Umeda, Atsushi Aoyama, Makoto Makishima, Yuichi Hashimoto, Minoru Ishikawa

研究成果: Article査読

15 被引用数 (Scopus)

抄録

Anti-inflammatory effects of liver X receptor (LXR) ligands are thought to be largely due to LXR-mediated transrepression, whereas side effects are caused by activation of LXR-responsive gene expression (transactivation). Therefore, selective LXR modulators that preferentially exhibit transrepression activity should exhibit anti-inflammatory properties with fewer side effects. Here, we synthesized a series of styrylphenylphthalimide analogues and evaluated their structure-activity relationships focusing on LXRs-transactivating-agonistic/antagonistic activities and transrepressional activity. Among the compounds examined, 17l showed potent LXR-transrepressional activity with high selectivity over transactivating activity and did not show characteristic side effects of LXR-transactivating agonists in cells. This representative compound, 17l, was confirmed to have LXR-dependent transrepressional activity and to bind directly to LXRβ. Compound 17l should be useful not only as a chemical tool for studying the biological functions of LXRs transrepression but also as a candidate for a safer agent to treat inflammatory diseases.

本文言語English
ページ(範囲)902-907
ページ数6
ジャーナルACS Medicinal Chemistry Letters
6
8
DOI
出版ステータスPublished - 2015 8 13
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 創薬
  • 有機化学

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