A structure-guided optimization of pyrido[2,3-d]pyrimidin-7-ones as selective inhibitors of EGFR(L858R/T790M) mutant with improved pharmacokinetic properties
文献类型：期刊论文
| 作者 | Yu, Lei1,2; Huang, Minhao1,2; Xu, Tianfeng1,2; Tong, Linjiang4; Yan, Xiao-e5,6; Zhang, Zhang1; Xu, Yong1; Yun, Caihong; Xie, Hua4 ; Ding, Ke1,3
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| 刊名 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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| 出版日期 | 2017-01-27 |
| 卷号 | 126页码:1107-1117 |
| 关键词 | EGFR(T790M) mutant Pyrido[2,3-d]pyrimidin-7-ones Pharmacokinetic property NSCLC Irreversible inhibitor |
| ISSN号 | 0223-5234 |
| DOI | 10.1016/j.ejmech.2016.12.006 |
| 文献子类 | Article |
| 英文摘要 | Structural optimization of pyrido[2,3-d]pyrimidin-7-ones was conducted to yield a series of new selective EGFR(T790M) inhibitors with improved pharmacokinetic properties. One of the most promising compound 9s potently suppressed EGFR(L858R/T790M) kinase and inhibited the proliferation of H1975 cells with IC50 values of 2.0 nM and 40 nM, respectively. The compound dose-dependently induced reduction of the phosphorylation of EGFR and downstream activation of ERIC in NCI-H1975 cells. It also exhibited moderate plasma exposure after oral administration and an oral bioavailability value of 16%. Compound 9s may serve as a promising lead compound for further drug discovery overcoming the acquired resistance of non-small cell lung cancer (NSCLC) patients. (C) 2016 Published by Elsevier Masson SAS. |
| WOS关键词 | GROWTH-FACTOR RECEPTOR ; CELL LUNG-CANCER ; 1ST GLOBAL APPROVAL ; EGFR INHIBITORS ; TYROSINE KINASE ; T790M-MEDIATED RESISTANCE ; BIOLOGICAL EVALUATION ; DISCOVERY ; POTENT ; PERSPECTIVES |
| 资助项目 | National High Technology Research and Development (863) for Young Scientists program[2015AA020906] ; Guangdong Province[2015A030306042] ; Guangdong Province[2014TQ01R341] ; Guangdong Province[2015A030312014] ; Guangzhou City[201508030036] ; Guangzhou City[201506010086] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000396804600085 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/275667]  |
| 专题 | 药理学第一研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Xie, Hua; Ding, Ke; Lu, Xiaoyun |
| 作者单位 | 1.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, 190 Kaiyuan Ave, Guangzhou 510530, Peoples R China; 2.Univ Chinese Acad Sci, 19 Yuquan Rd, Beijing 100049, Peoples R China; 3.Jinan Univ, Sch Pharm, 601 Huangpu Ave West, Guangzhou 510632, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zu Chong Zhi Rd,Zhangjiang Hi Tech Pk, Shanghai 201203, Peoples R China; 5.Peking Univ, Hlth Sci Ctr, Inst Syst Biomed, Beijing 100191, Peoples R China; 6.Peking Univ, Hlth Sci Ctr, Dept Biophys, Beijing 100191, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yu, Lei,Huang, Minhao,Xu, Tianfeng,et al. A structure-guided optimization of pyrido[2,3-d]pyrimidin-7-ones as selective inhibitors of EGFR(L858R/T790M) mutant with improved pharmacokinetic properties[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2017,126:1107-1117. |
| APA | Yu, Lei.,Huang, Minhao.,Xu, Tianfeng.,Tong, Linjiang.,Yan, Xiao-e.,...&Lu, Xiaoyun.(2017).A structure-guided optimization of pyrido[2,3-d]pyrimidin-7-ones as selective inhibitors of EGFR(L858R/T790M) mutant with improved pharmacokinetic properties.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,126,1107-1117. |
| MLA | Yu, Lei,et al."A structure-guided optimization of pyrido[2,3-d]pyrimidin-7-ones as selective inhibitors of EGFR(L858R/T790M) mutant with improved pharmacokinetic properties".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 126(2017):1107-1117. |
入库方式： OAI收割
来源：上海药物研究所
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