Identification of the KDM2/7 histone lysine demethylase subfamily inhibitor and its antiproliferative activity

Takayoshi Suzuki, Hiroki Ozasa, Yukihiro Itoh, Peng Zhan, Hideyuki Sawada, Koshiki Mino, Louise Walport, Rei Ohkubo, Akane Kawamura, Masato Yonezawa, Yuichi Tsukada, Anthony Tumber, Hidehiko Nakagawa, Makoto Hasegawa, Ryuzo Sasaki, Tamio Mizukami, Christopher J. Schofield, Naoki Miyata

研究成果: Contribution to journalArticle査読

58 被引用数 (Scopus)

抄録

Histone Nε-methyl lysine demethylases KDM2/7 have been identified as potential targets for cancer therapies. On the basis of the crystal structure of KDM7B, we designed and prepared a series of hydroxamate analogues bearing an alkyl chain. Enzyme assays revealed that compound 9 potently inhibits KDM2A, KDM7A, and KDM7B, with IC50s of 6.8, 0.2, and 1.2 μM, respectively. While inhibitors of KDM4s did not show any effect on cancer cells tested, the KDM2/7-subfamily inhibitor 9 exerted antiproliferative activity, indicating the potential for KDM2/7 inhibitors as anticancer agents.

本文言語英語
ページ(範囲)7222-7231
ページ数10
ジャーナルJournal of Medicinal Chemistry
56
18
DOI
出版ステータス出版済み - 9 26 2013

All Science Journal Classification (ASJC) codes

  • 分子医療
  • 創薬

フィンガープリント

「Identification of the KDM2/7 histone lysine demethylase subfamily inhibitor and its antiproliferative activity」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル