Discovery of Novel Class of METTL3 Inhibitors with a Pyridin-2(1H)-one Moiety
文献类型：期刊论文
| 作者 | Zhang, Weihang4; Huang, Yuting3,5; Yang, Hong3; Wan, Haiyan2; Lei, Xinsheng4; Xiang, Jinxi1,3; Wang, Yujie4; Li, Yingxia4; Huang, Xun1,3,5; Sun, Yu4 |
| 刊名 | ACS MEDICINAL CHEMISTRY LETTERS
 |
| 出版日期 | 2025-11-13 |
| 卷号 | 16期号:11页码:2257-2263 |
| 关键词 | Methyltransferase-like 3 METTL3-METTL14 complex scaffold hopping conformational constraint fragment growing |
| ISSN号 | 1948-5875 |
| DOI | 10.1021/acsmedchemlett.5c00465 |
| 英文摘要 | N 6-Methyladenosine methylation (m6A) is the most common type of RNA modification and is catalyzed primarily by the METTL3-METTL14 methyltransferase complex. METTL3 is considered a promising target for the treatment of acute myeloid leukemia (AML). However, only a few METTL3 inhibitors targeting the catalytic activity have been developed recently. Herein we report a series of novel METTL3 inhibitors bearing a pyridin-2(1H)-one moiety by structure-based drug design. Among these, compound 15 exhibits potent inhibitory activity against METTL3 (IC50 = 50 nM). Compound 15 shows moderate metabolic stability in mouse and human liver microsomes. Meanwhile, in MV411 and SKM1 cell lines, compound 15 is able to potently inhibit cell proliferation. These results make compound 15 a promising lead compound for further optimization. |
| WOS关键词 | TRANSLATION ; PROMOTES ; CANCER |
| 资助项目 | Program of Shanghai Subject Chief Scientist[22XD1425300] ; National Natural Science Foundation of China[82173835] ; Qingdao Marine Science and Technology Pilot National Laboratory Shandong Provincial Special Fund[2022QNLM030003-2] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001607648700001 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/319763]  |
| 专题 | 国家级研究中心_原创新药研究全国重点实验室 |
| 通讯作者 | Li, Yingxia; Huang, Xun; Sun, Yu |
| 作者单位 | 1.East China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Lingang Lab, Shanghai 200031, Peoples R China 4.Fudan Univ, Sch Pharm, Dept Med Chem, Shanghai 201203, Peoples R China 5.Shanghai Jiao Tong Univ, Sch Pharmaceut Sci, Shanghai 200240, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Weihang,Huang, Yuting,Yang, Hong,et al. Discovery of Novel Class of METTL3 Inhibitors with a Pyridin-2(1H)-one Moiety[J]. ACS MEDICINAL CHEMISTRY LETTERS,2025,16(11):2257-2263. |
| APA | Zhang, Weihang.,Huang, Yuting.,Yang, Hong.,Wan, Haiyan.,Lei, Xinsheng.,...&Sun, Yu.(2025).Discovery of Novel Class of METTL3 Inhibitors with a Pyridin-2(1H)-one Moiety.ACS MEDICINAL CHEMISTRY LETTERS,16(11),2257-2263. |
| MLA | Zhang, Weihang,et al."Discovery of Novel Class of METTL3 Inhibitors with a Pyridin-2(1H)-one Moiety".ACS MEDICINAL CHEMISTRY LETTERS 16.11(2025):2257-2263. |
入库方式： OAI收割
来源：上海药物研究所
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