YL143, a novel mutant selective irreversible EGFR inhibitor, overcomes EGFR(L858R, T790M)-mutant resistance in vitro and in vivo
文献类型：期刊论文
| 作者 | Zhang, Zhang2; Zou, Jian2; Yu, Lei1,5; Luo, Jinfeng1; Li, Yan4; Tu, Zhengchao1; Ren, Xiaomei2; Wei, Hongcheng3; Song, Liyan2; Lu, Xiaoyun2 |
| 刊名 | CANCER MEDICINE
 |
| 出版日期 | 2018-04 |
| 卷号 | 7期号:4页码:1430-1439 |
| 关键词 | EGFR inhibitor lung cancer pharmacokinetic selectively T790M mutation |
| ISSN号 | 2045-7634 |
| DOI | 10.1002/cam4.1392 |
| 文献子类 | Article |
| 英文摘要 | YL143 was identified as a novel wild-type sparing EGFR(T790M) inhibitor with good pharmacokinetic properties. It potently suppresses EGFR(L858R/T790M) with an 50% inhibitory concentration (IC50) value of 2.0 +/- 0.3nmol/L, but is approximately 92-folds less potent against EGFR(WT) kinase. YL143 suppresses cellular proliferation and induces G0/G1 phase arrest and apoptosis in H1975 cells with EGFR(L858R/T790M) mutation at 30nmol/L. It also exhibits acceptable pharmacokinetics (PK) parameters with an oral bioavailability value of 25.0% after oral administration in rats and exhibits promising antitumor efficacy in a gefitinib-resistant human H1975 xenografted model after oral administration of 30mg/kg/day. These data supported that YL143 could be a promising lead compound for overcoming clinical EGFR(T790M) resistance of patients with non-small-cell lung cancer (NSCLC). |
| WOS关键词 | CELL LUNG-CANCER ; TYROSINE KINASE INHIBITORS ; T790M-MEDIATED RESISTANCE ; ACQUIRED-RESISTANCE ; CLINICAL-RESPONSE ; GEFITINIB ; MUTATION ; THREONINE(790) ; CHEMOTHERAPY ; ERLOTINIB |
| 资助项目 | National High Technology Research and Development (863) for Young Scientists program[2015AA020906] ; National Natural Science Foundation of China[21572230] ; National Natural Science Foundation of China[81425021] ; Guangdong Province[2013A022100038] ; Guangdong Province[2015A030312014] ; Guangdong Province[2014TQ01R341] ; Guangdong Province[2] |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000430663300046 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279820]  |
| 专题 | 信息中心 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 药理学第一研究室 |
| 通讯作者 | Wei, Hongcheng; Song, Liyan; Lu, Xiaoyun; Ding, Ke |
| 作者单位 | 1.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, 190 Kaiyuan Ave,Guangzhou Sci Pk, Guangzhou 510530, Guangdong, Peoples R China; 2.Jinan Univ, Sch Pharm, 601 Huangpu Ave West, Guangzhou 510632, Guangdong, Peoples R China; 3.Jinan Univ, Affiliated Hosp 5, 613 Huangpu Ave West, Guangzhou 510630, Guangdong, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 5.Univ Chinese Acad Sci, 19 Yuquan Rd, Beijing 100049, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Zhang, Zhang,Zou, Jian,Yu, Lei,et al. YL143, a novel mutant selective irreversible EGFR inhibitor, overcomes EGFR(L858R, T790M)-mutant resistance in vitro and in vivo[J]. CANCER MEDICINE,2018,7(4):1430-1439. |
| APA | Zhang, Zhang.,Zou, Jian.,Yu, Lei.,Luo, Jinfeng.,Li, Yan.,...&Ding, Ke.(2018).YL143, a novel mutant selective irreversible EGFR inhibitor, overcomes EGFR(L858R, T790M)-mutant resistance in vitro and in vivo.CANCER MEDICINE,7(4),1430-1439. |
| MLA | Zhang, Zhang,et al."YL143, a novel mutant selective irreversible EGFR inhibitor, overcomes EGFR(L858R, T790M)-mutant resistance in vitro and in vivo".CANCER MEDICINE 7.4(2018):1430-1439. |
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。