2. Academic Validation
  3. Identification of the KDM2/7 histone lysine demethylase subfamily inhibitor and its antiproliferative activity

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

Affiliation

  • 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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