Identification of the KDM2/7 Histone Lysine Demethylase Subfamily Inhibitor and its Antiproliferative Activity

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• 作者：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
• 刊名：Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：September 26, 2013
• 年：2013
• 卷：56
• 期：18
• 页码：7222-7231
• 全文大小：512K
• 年卷期：v.56,no.18(September 26, 2013)
• ISSN：1520-4804

文摘

Histone N^蔚-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 渭M, 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.