A covalent compound selectively inhibits RNA demethylase ALKBH5 rather than FTO
文献类型：期刊论文
| 作者 | Lai, Gan-Qiang1,3; Li, Yali1; Zhu, Heping2; Zhang, Tao1; Gao, Jing1; Zhou, Hu1,2,3 ; Yang, Cai-Guang1,2,3,4
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| 刊名 | RSC CHEMICAL BIOLOGY
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| 出版日期 | 2024-04-03 |
| 卷号 | 5期号:4页码:335-343 |
| 关键词 | 有毒中药 吴茱萸 吴茱萸碱 吴茱萸次碱 减毒配伍 |
| DOI | 10.1039/d3cb00230f |
| 文献子类 | Article |
| 英文摘要 | N 6-Methyladenosine (m6A) is the most prevalent mRNA modification and is required for gene regulation in eukaryotes. ALKBH5, an m6A demethylase, is a promising target, particularly for anticancer drug discovery. However, the development of selective and potent inhibitors of ALKBH5 rather than FTO remains challenging. Herein, we used a targeted covalent inhibition strategy and identified a covalent inhibitor, TD19, which selectively inhibits ALKBH5 compared with FTO demethylase in protein-based and tumor cell-based assays. TD19 irreversibly modifies the residues C100 and C267, preventing ALKBH5 from binding to m6A-containing RNA. Moreover, TD19 displays good anticancer efficacy in acute myeloid leukemia and glioblastoma multiforme cell lines. Thus, the ALKBH5 inhibitor developed in this study, which selectively targets ALKBH5 compared with FTO, can potentially be used as a probe for investigating the biological functions of RNA demethylase and as a lead compound in anticancer research.We discovered that TD19 covalently and selectively inhibits ALKBH5 rather than FTO demethylase in both protein-based and tumor cell-based assays. |
| WOS关键词 | CRYSTAL-STRUCTURE ; NUCLEAR-RNA ; METABOLISM ; MECHANISMS ; SUBSTRATE ; CELLS |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:001165648800001 |
| 出版者 | ROYAL SOC CHEMISTRY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/317022]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Yang, Cai-Guang |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Peoples R China |
| 推荐引用方式 GB/T 7714 | Lai, Gan-Qiang,Li, Yali,Zhu, Heping,et al. A covalent compound selectively inhibits RNA demethylase ALKBH5 rather than FTO[J]. RSC CHEMICAL BIOLOGY,2024,5(4):335-343. |
| APA | Lai, Gan-Qiang.,Li, Yali.,Zhu, Heping.,Zhang, Tao.,Gao, Jing.,...&Yang, Cai-Guang.(2024).A covalent compound selectively inhibits RNA demethylase ALKBH5 rather than FTO.RSC CHEMICAL BIOLOGY,5(4),335-343. |
| MLA | Lai, Gan-Qiang,et al."A covalent compound selectively inhibits RNA demethylase ALKBH5 rather than FTO".RSC CHEMICAL BIOLOGY 5.4(2024):335-343. |
入库方式： OAI收割
来源：上海药物研究所
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