Design and structural optimization of thiadiazole derivatives with potent GLS1 inhibitory activity

Takuya Okada*, Kaho Yamabe, Michiko Jo, Yuko Sakajiri, Tomokazu Shibata, Ryusuke Sawada, Yoshihiro Yamanishi, Daisuke Kanayama, Hisashi Mori, Mineyuki Mizuguchi, Takayuki Obita, Yuko Nabeshima, Keiichi Koizumi, Naoki Toyooka

*この論文の責任著者

研究成果: ジャーナルへの寄稿学術論文査読

1 被引用数 (Scopus)

抄録

GLS1 is an attractive target not only as anticancer agents but also as candidates for various potential pharmaceutical applications such as anti-aging and anti-obesity treatments. We performed docking simulations based on the complex crystal structure of GLS1 and its inhibitor CB-839 and found that compound A bearing a thiadiazole skeleton exhibits GLS1 inhibition. Furthermore, we synthesized 27 thiadiazole derivatives in an effort to obtain a more potent GLS1 inhibitor. Among the synthesized derivatives, 4d showed more potent GLS1 inhibitory activity (IC50 of 46.7 µM) than known GLS1 inhibitor DON and A. Therefore, 4d is a very promising novel GLS1 inhibitor.

本文言語英語
論文番号129438
ジャーナルBioorganic and Medicinal Chemistry Letters
93
DOI
出版ステータス出版済み - 2023/09/01

ASJC Scopus 主題領域

  • 生化学
  • 分子医療
  • 分子生物学
  • 薬科学
  • 創薬
  • 臨床生化学
  • 有機化学

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