Structure-Based of a Series of NSD2-PWWP1 Inhibitors
文献类型：期刊论文
| 作者 | Li, Na1,2; Yang, Hong3; Liu, Ke4; Zhou, Liwei1; Huang, Yuting3; Cao, Danyan1; Li, Yanlian1; Sun, Yaoliang5; Yu, Aisong3; Du, Zhiyan1 |
| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2022-06-15 |
| 卷号 | 65期号:13页码:9459-9477 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/acs.jmedchem.2c00709 |
| 文献子类 | Article |
| 英文摘要 | Overexpression, point mutations, or translocations of protein lysine methyltransferase NSD2 occur in many types of cancer cells. Therefore, it was recognized as onco-protein and considered as a promising anticancer drug target. NSD2 consists of multiple domains including a SET catalytic domain and two PWWP domains binding to methylated histone proteins. Here, we reported our efforts to develop a series of NSD2-PWWP1 inhibitors, and further structure-based optimization resulted in a potent inhibitor 38, which has high selectivity toward the NSD2-PWWP1 domain. The detailed biological evaluation revealed that compound 38 can bind to NSD2-PWWP1 and then affect the expression of genes regulated by NSD2. The current discovery will provide a useful chemical probe to the future research in understanding the specific regulation mode of NSD2 by PWWP1 recognition and pave the way to develop potential drugs targeting NSD2 protein. |
| WOS关键词 | METHYLTRANSFERASE NSD2 ; HISTONE |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| 出版者 | AMER CHEMICAL SOC |
| WOS记录号 | WOS:000821469600001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309336]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Xiong, Bing; Xu, Shilin; Huang, Xun; Liu, Tongchao |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, Shanghai 201203, Peoples R China; 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 4.Chinese Acad Sci, Shanghai Adv Res Inst, Shanghai Synchrotron Radiat Facil, Shanghai 201210, Peoples R China; 5.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 6.UCAS, Hangzhou Inst Adv Study, Hangzhou 310024, Peoples R China; 7.Gannan Med Univ, Coll Pharmaceut Sci, Ganzhou 341000, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Na,Yang, Hong,Liu, Ke,et al. Structure-Based of a Series of NSD2-PWWP1 Inhibitors[J]. JOURNAL OF MEDICINAL CHEMISTRY,2022,65(13):9459-9477. |
| APA | Li, Na.,Yang, Hong.,Liu, Ke.,Zhou, Liwei.,Huang, Yuting.,...&Liu, Tongchao.(2022).Structure-Based of a Series of NSD2-PWWP1 Inhibitors.JOURNAL OF MEDICINAL CHEMISTRY,65(13),9459-9477. |
| MLA | Li, Na,et al."Structure-Based of a Series of NSD2-PWWP1 Inhibitors".JOURNAL OF MEDICINAL CHEMISTRY 65.13(2022):9459-9477. |
入库方式： OAI收割
来源：上海药物研究所
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