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

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 Miyata

doi:10.1021/jm400624b

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

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 Miyata

先端生命情報研究部門（特定教育研究部門）

研究成果: Contribution to journal › Article › 査読

58 被引用数 (Scopus)

抄録

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.

本文言語	英語
ページ（範囲）	7222-7231
ページ数	10
ジャーナル	Journal of Medicinal Chemistry
巻	56
号	18
DOI	https://doi.org/10.1021/jm400624b
出版ステータス	出版済み - 9 26 2013

All Science Journal Classification (ASJC) codes

分子医療
創薬

UN SDG

この成果は、次の持続可能な開発目標に貢献しています

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10.1021/jm400624b

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Suzuki, T., Ozasa, H., Itoh, Y., Zhan, P., Sawada, H., Mino, K., Walport, L., Ohkubo, R., Kawamura, A., Yonezawa, M., Tsukada, Y., Tumber, A., Nakagawa, H., Hasegawa, M., Sasaki, R., Mizukami, T., Schofield, C. J., & Miyata, N. (2013). Identification of the KDM2/7 histone lysine demethylase subfamily inhibitor and its antiproliferative activity. Journal of Medicinal Chemistry, 56(18), 7222-7231. https://doi.org/10.1021/jm400624b

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

In: Journal of Medicinal Chemistry, Vol. 56, No. 18, 26.09.2013, p. 7222-7231.

研究成果: Contribution to journal › Article › 査読

Suzuki, T, Ozasa, H, Itoh, Y, Zhan, P, Sawada, H, Mino, K, Walport, L, Ohkubo, R, Kawamura, A, Yonezawa, M, Tsukada, Y, Tumber, A, Nakagawa, H, Hasegawa, M, Sasaki, R, Mizukami, T, Schofield, CJ & Miyata, N 2013, 'Identification of the KDM2/7 histone lysine demethylase subfamily inhibitor and its antiproliferative activity', Journal of Medicinal Chemistry, vol. 56, no. 18, pp. 7222-7231. https://doi.org/10.1021/jm400624b

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. / Identification of the KDM2/7 histone lysine demethylase subfamily inhibitor and its antiproliferative activity. In: Journal of Medicinal Chemistry. 2013 ; Vol. 56, No. 18. pp. 7222-7231.

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abstract = "Histone Nε-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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AU - Yonezawa, Masato

AU - Tsukada, Yuichi

AU - Tumber, Anthony

AU - Nakagawa, Hidehiko

AU - Hasegawa, Makoto

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AB - Histone Nε-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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Identification of the KDM2/7 histone lysine demethylase subfamily inhibitor and its antiproliferative activity

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All Science Journal Classification (ASJC) codes

UN SDG

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