Antitumor activity of a new N-substituted thiourea derivative, an EGFR signaling-targeted inhibitor against a panel of human lung cancer cell lines
文献类型：期刊论文
| 作者 | Xiong, Xishan2; Liu, Hong1 ; Fu, Lili2; Li, Lin2; Li, Jian1; Luo, Xiaomin1; Mei, Changlin2
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| 刊名 | CHEMOTHERAPY
 |
| 出版日期 | 2008 |
| 卷号 | 54期号:6页码:463-474 |
| 关键词 | EGFR tyrosine kinase inhibitor non-small-cell lung cancer IC50 Erk1/2 AKT |
| ISSN号 | 0009-3157 |
| DOI | 10.1159/000159272 |
| 文献子类 | Article |
| 英文摘要 | Epidermal growth factor receptor (EGFR) is one of the important protein tyrosine kinases (PTKs), whose blockade by tyrosine kinase inhibitors (TKIs) has been introduced in the treatment of advanced non-small-cell lung cancers (NSCLCs). However, intrinsic and acquired resistance to the clinically used erlotinib or gefitinib leads to poor overall prognosis. The novel EGFR-TKI will provide alternative choices in NSCLC treatment and might be beneficial. We have previously reported the design and synthesis of a novel class of PTK inhibitors featuring the N-(2-oxo-1,2-dihydro-quinolin-3-ylmethyl)thiourea framework. In this study, we examined the antitumor effect of compound 5a (DC27) in a panel of human lung carcinoma cell lines. The results of a bromodeoxy-urdine (BrdU) incorporation assay revealed that cell proliferation was inhibited in a dose-dependent manner, with an IC50 of 2.5-12.9 mu M, similar to gefitinib (1.1-15.6 mu M). DC27 induced G(0)/G(1) arrest of cell cycle and apoptosis as tested by flow cytometry. DC27 markedly reduced tyrosine phosphorylation of EGFR and inhibited activation of Erk1/2 and AKT, two key downstream effectors of proliferation. In conclusion, DC27 has potent in vitro cytotoxicity against human lung carcinoma cells, possibly mediated by induction of apoptosis and cell cycle arrest in G(0)/G(1) phase. Copyright (C) 2008 S. Karger AG, Basel. |
| WOS关键词 | GROWTH-FACTOR RECEPTOR ; TYROSINE KINASE INHIBITORS ; PHASE-II ; GEFITINIB ; ERLOTINIB ; DESIGN ; DETERMINANTS ; THERAPY ; FAILURE ; DRUGS |
| 资助项目 | National 863 Plan in High Technology Progress[2002AA2Z3130] ; National 863 Plan in High Technology Progress[2007AA02Z3Z1] ; Shanghai Leading Academic[B902] |
| WOS研究方向 | Oncology ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000259876600009 |
| 出版者 | KARGER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/273016]  |
| 专题 | 药物化学研究室 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 药物发现与设计中心 |
| 通讯作者 | Mei, Changlin |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Grad Sch,Drug Discovery & Design Ctr, Shanghai 200031, Peoples R China 2.Second Mil Med Univ, Changzheng Hosp, Dept Internal Med, Nephrol Inst PLA, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Xiong, Xishan,Liu, Hong,Fu, Lili,et al. Antitumor activity of a new N-substituted thiourea derivative, an EGFR signaling-targeted inhibitor against a panel of human lung cancer cell lines[J]. CHEMOTHERAPY,2008,54(6):463-474. |
| APA | Xiong, Xishan.,Liu, Hong.,Fu, Lili.,Li, Lin.,Li, Jian.,...&Mei, Changlin.(2008).Antitumor activity of a new N-substituted thiourea derivative, an EGFR signaling-targeted inhibitor against a panel of human lung cancer cell lines.CHEMOTHERAPY,54(6),463-474. |
| MLA | Xiong, Xishan,et al."Antitumor activity of a new N-substituted thiourea derivative, an EGFR signaling-targeted inhibitor against a panel of human lung cancer cell lines".CHEMOTHERAPY 54.6(2008):463-474. |
入库方式： OAI收割
来源：上海药物研究所
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