Proteome-Wide Ligand and Target Discovery by Using Covalent Probes and Natural Products
文献类型：期刊论文
| 作者 | Liu, Jingqing4,5,6; Huang, Chaoming4,5,6; Li, Shengrong3; Peng, Lijie4,5,6; Sun, Yaoliang2; Yang, Jianzhang4,5,6; Li, Shan4,5,6; Xu, Shilin2; Lu, Xiaoyun4,5,6; Ding, Ke4,5,6 |
| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2025-10-09 |
| 卷号 | 68期号:19页码:20228-20242 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/acs.jmedchem.5c01277 |
| 通讯作者 | Xu, Shilin(pharmlzq@jnu.edu.cn) ; Li, Zhengqiu(slxu@simm.ac.cn) |
| 英文摘要 | Due to the lack of effective therapeutic targets for drug development, many diseases remain difficult to treat. To address this issue, phenotypic screening integrated with chemical proteomics has emerged as an efficient strategy to expand the scope of druggable targets. In this study, we constructed a covalent probe library based on diverse covalent kinase inhibitors and natural products containing an alpha, beta-unsaturated ketone electrophilic warhead. Antiproliferation screening revealed that these probes exhibit potent anticancer activity against triple-negative breast cancer (TNBC) and human colon cancer. Subsequent proteomic studies identified a series of novel covalently ligandable targets, including ASNS, AKR1C1, DDX39B, and PRMT5. Functional validation demonstrated that DDX39B may represent a new therapeutic target for TNBC. Moreover, we identified a series of highly selective covalent probes targeting ARK1C1, PDIA1, and ALDH1A1, which could serve as valuable tools for detecting the expression and activity of these critical proteins. |
| WOS关键词 | CANCER ; DERIVATIVES ; BRITANNIN ; REVEALS |
| 资助项目 | National Natural Science Foundation of China[22277040] ; National Natural Science Foundation of China[22277128] ; Natural Science Foundation of China[2023B1515120023] ; Science and Technology Program of Guangdong Province[2023B1515040016] ; Guangdong Basic and Applied Basic Research Foundation |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001579178500001 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/321552]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Xu, Shilin; Li, Zhengqiu |
| 作者单位 | 1.Jinan Univ, Int Cooperat Lab Tradit Chinese Med Modernizat & I, MOE Key Lab Tumor Mol Biol, Guangzhou 510632, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, Shanghai 201203, Peoples R China 3.Jinan Univ, Guangdong Prov Gen Hosp 2, Postdoctoral Stn Tradit Chinese Med, Guangzhou 510632, Peoples R China 4.Jinan Univ, Sch Pharm, Guangzhou 510632, Peoples R China 5.Jinan Univ, Int Cooperat Lab Tradit Chinese Med Modernizat & I, Guangzhou 510632, Peoples R China 6.Jinan Univ, State Key Lab Bioact Mol & Druggabil Assessment, Guangzhou 510632, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Jingqing,Huang, Chaoming,Li, Shengrong,et al. Proteome-Wide Ligand and Target Discovery by Using Covalent Probes and Natural Products[J]. JOURNAL OF MEDICINAL CHEMISTRY,2025,68(19):20228-20242. |
| APA | Liu, Jingqing.,Huang, Chaoming.,Li, Shengrong.,Peng, Lijie.,Sun, Yaoliang.,...&Li, Zhengqiu.(2025).Proteome-Wide Ligand and Target Discovery by Using Covalent Probes and Natural Products.JOURNAL OF MEDICINAL CHEMISTRY,68(19),20228-20242. |
| MLA | Liu, Jingqing,et al."Proteome-Wide Ligand and Target Discovery by Using Covalent Probes and Natural Products".JOURNAL OF MEDICINAL CHEMISTRY 68.19(2025):20228-20242. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。