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

  • J Med Chem. 2013 Sep 26;56(18):7222-31. doi: 10.1021/jm400624b.
Takayoshi Suzuki  1 ,  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
Affiliations
  • 1. Graduate School of Medical Science, Kyoto Prefectural University of Medicine , 13 Taishogun Nishitakatsukasa-Cho, Kita-ku, Kyoto 603-8334, Japan.
PMID: 23964788 DOI: 10.1021/jm400624b
Abstract

Histone N(ε)-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.

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