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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...
| Autores principales: | , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
American
Chemical Society
2013
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| 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 |
| _version_ | 1782304357232934912 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Suzuki, Takayoshi |
| collection | PubMed |
| description | [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. |
| format | Online Article Text |
| id | pubmed-3929130 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2013 |
| publisher | American
Chemical Society |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-39291302014-02-20 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 J Med Chem [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. American Chemical Society 2013-08-21 2013-09-26 /pmc/articles/PMC3929130/ /pubmed/23964788 http://dx.doi.org/10.1021/jm400624b Text en Copyright © 2013 American Chemical Society Terms of Use CC-BY (http://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html) |
| spellingShingle | 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 |
| title | Identification
of the KDM2/7 Histone Lysine Demethylase
Subfamily Inhibitor and its Antiproliferative Activity |
| title_full | Identification
of the KDM2/7 Histone Lysine Demethylase
Subfamily Inhibitor and its Antiproliferative Activity |
| title_fullStr | Identification
of the KDM2/7 Histone Lysine Demethylase
Subfamily Inhibitor and its Antiproliferative Activity |
| title_full_unstemmed | Identification
of the KDM2/7 Histone Lysine Demethylase
Subfamily Inhibitor and its Antiproliferative Activity |
| title_short | Identification
of the KDM2/7 Histone Lysine Demethylase
Subfamily Inhibitor and its Antiproliferative Activity |
| title_sort | identification
of the kdm2/7 histone lysine demethylase
subfamily inhibitor and its antiproliferative activity |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3929130/ https://www.ncbi.nlm.nih.gov/pubmed/23964788 http://dx.doi.org/10.1021/jm400624b |
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