Discovery of JND3229 as a New EGFR(C797S) Mutant Inhibitor with In Vivo Monodrug Efficacy
文献类型：期刊论文
| 作者 | Lu, Xiaoyun2; Zhang, Tao1,3,7; Zhu, Su-Jie4,5; Xun, Qiuju6; Tong, Lingjiang3; Hu, Xianglong2; Li, Yan3; Chan, Shingpan2; Su, Yi3; Sun, Yiming3 |
| 刊名 | ACS MEDICINAL CHEMISTRY LETTERS
 |
| 出版日期 | 2018-11 |
| 卷号 | 9期号:11页码:1123-1127 |
| 关键词 | EGFR(C797s) Clinical resistance Fourth-generation nhibitors Monodrug efficacy |
| ISSN号 | 1948-5875 |
| DOI | 10.1021/acsmedchemlett.8b00373 |
| 文献子类 | Article |
| 英文摘要 | EGFR(C797S) mutation inducing resistance against third generation EGFR inhibitor drugs is an emerging "unmet clinical need" for nonsmall cell lung cancer patients. The pyrimidopyrimidinone derivative JND3229 was identified as a new highly potent EGFR(C797S) inhibitor with single digit nM potency. It also exhibited good in vitro and in vivo monodrug anticancer efficacy in a xenograft mouse model of BaF3/EGFR(19D/T70M/C797S) cells. A high-resolution X-ray crystallographic structure was also determined to elucidate the interactions between JND3229 and EGFR(T790M/C797S). Our study provides an important structural and chemical basis for future development of new generation EGFR(C797S) inhibitors as anticancer drugs. |
| WOS关键词 | CELL LUNG-CANCER ; IMPROVED PHARMACOKINETIC PROPERTIES ; EGFR INHIBITORS ; BIOLOGICAL EVALUATION ; SELECTIVE INHIBITORS ; RECEPTOR INHIBITORS ; C797S RESISTANCE ; DERIVATIVES ; MUTATION ; DESIGN |
| 资助项目 | Guangdong Natural Science Funds[2015A030306042] ; Guangdong Natural Science Funds[2105A030312014] ; National Natural Science Foundation of China[21572230] ; National Natural Science Foundation of China[81425021] ; National Natural Science Foundation of China[21702075] ; National Natural Science Foundation of China[81673285] ; National Natural Science Foundation of China[31270769] ; Guangdong Nanyue-Baijie Award[00000000] ; Guangzhou City Key Laboratory of Precision Chemical Drug Development[201805010007] ; Institutes for Drug Discovery and Development of Chinese Academy of Science[CASIMM0120185006] ; Jinan University[00000000] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000449888400011 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279511]  |
| 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 | Lu, Xiaoyun; Yun, Cai-Hong; Xie, Hua; Ding, Ke |
| 作者单位 | 1.Univ Chinese Acad Sci, Sch Pharm, 19A Yuquan Rd, Beijing 100049, Peoples R China 2.Jinan Univ, Sch Pharm, Chinese Minist Educ MOE, Int Cooperat Lab Tradit Chinese Med Modernizat &, 601 Huangpu Ave West, Guangzhou 510632, Guangdong, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, 555 Chong Zhi Rd, Shanghai 201203, Peoples R China; 4.Peking Univ, Hlth Sci Ctr, Dept Biophys, Beijing 100191, Peoples R China; 5.Peking Univ, Hlth Sci Ctr, Inst Syst Biomed, Beijing 100191, Peoples R China; 6.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, 190 Kaiyuan Ave, Guangzhou 510530, Guangdong, Peoples R China; 7.ShanghaiTech Univ, Sch Life Sci & Technol, 393 Middle Huaxia Rd, Shanghai 201210, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Lu, Xiaoyun,Zhang, Tao,Zhu, Su-Jie,et al. Discovery of JND3229 as a New EGFR(C797S) Mutant Inhibitor with In Vivo Monodrug Efficacy[J]. ACS MEDICINAL CHEMISTRY LETTERS,2018,9(11):1123-1127. |
| APA | Lu, Xiaoyun.,Zhang, Tao.,Zhu, Su-Jie.,Xun, Qiuju.,Tong, Lingjiang.,...&Ding, Ke.(2018).Discovery of JND3229 as a New EGFR(C797S) Mutant Inhibitor with In Vivo Monodrug Efficacy.ACS MEDICINAL CHEMISTRY LETTERS,9(11),1123-1127. |
| MLA | Lu, Xiaoyun,et al."Discovery of JND3229 as a New EGFR(C797S) Mutant Inhibitor with In Vivo Monodrug Efficacy".ACS MEDICINAL CHEMISTRY LETTERS 9.11(2018):1123-1127. |
入库方式： OAI收割
来源：上海药物研究所
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