Design, synthesis and biological study of potent and covalent HER-2 tyrosine kinase inhibitors with low cytotoxicity in vitro
文献类型：期刊论文
| 作者 | Jin, Shuyu2,3; Sun, Xiuyun1,3; Liu, Dan2; Xie, Hua4 ; Rao, Yu3
|
| 刊名 | CHEMICAL PAPERS
 |
| 出版日期 | 2019-06-01 |
| 卷号 | 73期号:6页码:1333-1345 |
| 关键词 | HER-2 inhibitors 4-Anilino-3-cyanoquinoline Covalent Anticancer activity |
| ISSN号 | 2585-7290 |
| DOI | 10.1007/s11696-019-00686-0 |
| 通讯作者 | Liu, Dan(sammyld@163.com) ; Xie, Hua(hxie@simm.ac.cn) ; Rao, Yu(yrao@mail.tsinghua.edu.cn) |
| 英文摘要 | The discovery and development of a novel HER-2 tyrosine kinase inhibitor for the treatment of HER2-positive breast cancer are presented in this article. EGFR family has been recognized as a crucial meditator in the cancer progression; HER-2 tyrosine kinase was one of the members among them. In the effort to explore potent HER-2 inhibitors, a novel series of 4-anilino-3-cyanoquinoline derivatives have been designed, synthesized and evaluated. Most compounds possessed modest proliferation inhibition on SK-BR-3 cell line and HER-2 kinase. Compound 16 appeared to be the most potent compound (HER-2 kinase IC50: 19.4nM, SK-BR-3 IC50: 94nM). In the experiment of cellular cytotoxicity assay, compound 16 shows a much lower cytotoxicity than neratinib on Beas-2b cell line (Human bronchial epithelial cells). In conclusion, compound 16 would be a promising lead compound for further anti-breast cancer drug discovery. |
| WOS关键词 | HER2-POSITIVE BREAST-CANCER ; NERATINIB HKI-272 ; TRASTUZUMAB ; THERAPIES ; EFFICACY ; SAFETY |
| 资助项目 | National Natural Science Foundation of China[81573277] ; National Natural Science Foundation of China[81622042] ; National Natural Science Foundation of China[81773567] ; National Major Scientific and Technological Special Project for Significant New Drugs Development[SQ2017ZX095003] ; Tsinghua University Initiative Scientific Research Program |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000468514800003 |
| 出版者 | SPRINGER INTERNATIONAL PUBLISHING AG |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/289810]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Liu, Dan; Xie, Hua; Rao, Yu |
| 作者单位 | 1.Tsinghua Peking Ctr Life Sci, Beijing 100084, Peoples R China 2.Shenyang Pharmaceut Univ, Minist Educ, Key Lab Struct Based Drugs Design & Discovery, 103 Wenhua Rd, Shenyang 110016, Liaoning, Peoples R China 3.Tsinghua Univ, MOE Key Lab Bioorgan Phosphorus Chem & Chem Biol, Sch Pharmaceut Sci, MOE Key Lab Prot Sci, Beijing 100084, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Jin, Shuyu,Sun, Xiuyun,Liu, Dan,et al. Design, synthesis and biological study of potent and covalent HER-2 tyrosine kinase inhibitors with low cytotoxicity in vitro[J]. CHEMICAL PAPERS,2019,73(6):1333-1345. |
| APA | Jin, Shuyu,Sun, Xiuyun,Liu, Dan,Xie, Hua,&Rao, Yu.(2019).Design, synthesis and biological study of potent and covalent HER-2 tyrosine kinase inhibitors with low cytotoxicity in vitro.CHEMICAL PAPERS,73(6),1333-1345. |
| MLA | Jin, Shuyu,et al."Design, synthesis and biological study of potent and covalent HER-2 tyrosine kinase inhibitors with low cytotoxicity in vitro".CHEMICAL PAPERS 73.6(2019):1333-1345. |
入库方式： OAI收割
来源：上海药物研究所
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