Identification of the KDM2/7 histone lysine demethylase subfamily inhibitor and its antiproliferative activity
Authors list
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 MiyataAbstract
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.
Journal details
Journal Journal of Medicinal Chemistry
Volume 56
Issue number 18
Pages 7222-7231
Publication date
Full text links
Publisher website (DOI) 10.1021/jm400624b
Europe PubMed Central 23964788
Pubmed 23964788
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