title: Identification of the KDM2/7 histone lysine demethylase subfamily inhibitor and its antiproliferative activity.
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.
authors: Graduate School of Medical Science, Kyoto Prefectural University of Medicine , 13 Taishogun Nishitakatsukasa-Cho, Kita-ku, Kyoto 603-8334, Japan.
authors: Takayoshi
authors: T
authors: Suzuki
authors: Hiroki
authors: H
authors: Ozasa
authors: Yukihiro
authors: Y
authors: Itoh
authors: Peng
authors: P
authors: Zhan
authors: Hideyuki
authors: H
authors: Sawada
authors: Koshiki
authors: K
authors: Mino
authors: Louise
authors: L
authors: Walport
authors: Rei
authors: R
authors: Ohkubo
authors: Akane
authors: A
authors: Kawamura
authors: Masato
authors: M
authors: Yonezawa
authors: Yuichi
authors: Y
authors: Tsukada
authors: Anthony
authors: A
authors: Tumber
authors: Hidehiko
authors: H
authors: Nakagawa
authors: Makoto
authors: M
authors: Hasegawa
authors: Ryuzo
authors: R
authors: Sasaki
authors: Tamio
authors: T
authors: Mizukami
authors: Christopher J
authors: CJ
authors: Schofield
authors: Naoki
authors: N
authors: Miyata
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D056466:Histone Demethylases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D056466:Histone Demethylases
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