Identification of the KDM2/7 histone lysine demethylase subfamily inhibitor and its antiproliferative activity.
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 K...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2013
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| _version_ | 1797055482514374656 |
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| author | 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 Miyata, N |
| author_facet | 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 Miyata, N |
| author_sort | Suzuki, T |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T19:11:18Z |
| format | Journal article |
| id | oxford-uuid:16dafeed-c83e-4685-b573-e6034787e6cf |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:11:18Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | oxford-uuid:16dafeed-c83e-4685-b573-e6034787e6cf2022-03-26T10:33:52ZIdentification of the KDM2/7 histone lysine demethylase subfamily inhibitor and its antiproliferative activity.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:16dafeed-c83e-4685-b573-e6034787e6cfEnglishSymplectic Elements at Oxford2013Suzuki, TOzasa, HItoh, YZhan, PSawada, HMino, KWalport, LOhkubo, RKawamura, AYonezawa, MTsukada, YTumber, ANakagawa, HHasegawa, MSasaki, RMizukami, TSchofield, CMiyata, NHistone 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. |
| spellingShingle | 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 Miyata, N 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 |
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