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

[Image: see text] 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 p...

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Detalles Bibliográficos
Autores principales: Suzuki, Takayoshi, Ozasa, Hiroki, Itoh, Yukihiro, Zhan, Peng, Sawada, Hideyuki, Mino, Koshiki, Walport, Louise, Ohkubo, Rei, Kawamura, Akane, Yonezawa, Masato, Tsukada, Yuichi, Tumber, Anthony, Nakagawa, Hidehiko, Hasegawa, Makoto, Sasaki, Ryuzo, Mizukami, Tamio, Schofield, Christopher J., Miyata, Naoki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2013
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3929130/
https://www.ncbi.nlm.nih.gov/pubmed/23964788
http://dx.doi.org/10.1021/jm400624b
Descripción
Sumario:[Image: see text] 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 IC(50)s 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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