Structure-Based Design of 5-Methylpyrimidopyridone Derivatives as New Wild-Type Sparing Inhibitors of the Epidermal Growth Factor Receptor Triple Mutant (EGFR(L858R/T790M/C797S))
文献类型：期刊论文
| 作者 | Shen, Jiayi1; Zhang, Tao2; Zhu, Su-Jie3; Sun, Min4; Tong, Linjiang2; Lai, Mengzhen2; Zhang, Rong5; Xu, Wei1; Wu, Ruibo5; Ding, Jian2
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| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
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| 出版日期 | 2019-08-08 |
| 卷号 | 62期号:15页码:7302-7308 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/acs.jmedchem.9b00576 |
| 通讯作者 | Yun, Cai-Hong(yunch@bjmu.edu.cn) ; Xie, Hua(hxie@simm.ac.cn) ; Lu, Xiaoyun(luxy2016@jnu.edu.cn) ; Ding, Ke(dingke@jnu.edu.cn) |
| 英文摘要 | Tertiary EGFRc797s mutation induced resistance against osimertinib (1) is an emerging "unmet clinical need" for non-small-cell lung cancer (NSCLC) patients. A series of 5-methylpyrimidopyridone derivatives were designed and synthesized as new selective EGFR(L858R/T790M/C797S) inhibitors. A representative compound, 8r-B, exhibited an ICso of 27.5 nM against the EGFR(L858R/T790M/C797S) mutant, while being a significantly less potent for EGFRwr (IC50 > 1.0 NM). Cocrystallographic structure determination and computational investigation were conducted to elucidate its target selectivity. |
| WOS关键词 | LUNG-CANCER ; EGFR INHIBITORS ; RESISTANCE ; GEFITINIB ; OPTIMIZATION ; DISCOVERY ; MUTATIONS ; AZD9291 |
| 资助项目 | National Natural Science Foundation of China[81820108029] ; National Natural Science Foundation of China[21572230] ; National Natural Science Foundation of China[81673285] ; National Natural Science Foundation of China[81425021] ; National Natural Science Foundation of China[21702075] ; Guangdong Province[2015A030312014] ; Guangdong Province[2015A030306042] ; Guangdong Province[2016A050502041] ; Guangdong Province[2018A050506043] ; Guangdong Province[2017A030310253] ; Guangzhou City[201805010007] ; Jinan University |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000480500600029 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/288972]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Yun, Cai-Hong; Xie, Hua; Lu, Xiaoyun; Ding, Ke |
| 作者单位 | 1.Jinan Univ, Sch Pharm, Guangzhou City Key Lab Precis Chem Drug Dev,Minis, Int Cooperat Lab Tradit Chinese Med Modernizat &, 601 Huangpu Ave West, Guangzhou 510632, Guangdong, Peoples R China 2.Chinese Acad Sci, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai Inst Mat Med, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 3.Qingdao Univ, Inst Translat Med, Coll Med, Qingdao 266021, Shandong, Peoples R China 4.Jiangsu Aosaikang Pharmacceut Co Ltd, 699 Kejian Rd,Jiangsu Sci Pk, Nanjing 211112, Jiangsu, Peoples R China 5.Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China 6.Peking Univ, Hlth Sci Ctr, Dept Biochem & Biophys, Inst Syst Biomed,Sch Basic Med Sci, Beijing 100191, Peoples R China |
| 推荐引用方式 GB/T 7714 | Shen, Jiayi,Zhang, Tao,Zhu, Su-Jie,et al. Structure-Based Design of 5-Methylpyrimidopyridone Derivatives as New Wild-Type Sparing Inhibitors of the Epidermal Growth Factor Receptor Triple Mutant (EGFR(L858R/T790M/C797S))[J]. JOURNAL OF MEDICINAL CHEMISTRY,2019,62(15):7302-7308. |
| APA | Shen, Jiayi.,Zhang, Tao.,Zhu, Su-Jie.,Sun, Min.,Tong, Linjiang.,...&Ding, Ke.(2019).Structure-Based Design of 5-Methylpyrimidopyridone Derivatives as New Wild-Type Sparing Inhibitors of the Epidermal Growth Factor Receptor Triple Mutant (EGFR(L858R/T790M/C797S)).JOURNAL OF MEDICINAL CHEMISTRY,62(15),7302-7308. |
| MLA | Shen, Jiayi,et al."Structure-Based Design of 5-Methylpyrimidopyridone Derivatives as New Wild-Type Sparing Inhibitors of the Epidermal Growth Factor Receptor Triple Mutant (EGFR(L858R/T790M/C797S))".JOURNAL OF MEDICINAL CHEMISTRY 62.15(2019):7302-7308. |
入库方式： OAI收割
来源：上海药物研究所
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