Acenaphtho[1,2-b]pyrrole-Based Selective Fibroblast Growth Factor Receptors 1 (FGFR1) Inhibitors: Design, Synthesis, and Biological Activity
文献类型：期刊论文
| 作者 | Chen, Zhuo1,2; Wang, Xin2 ; Zhu, Weiping2; Cao, Xianwen2; Tong, Linjiang1; Li, Honglin2; Xie, Hua1; Xu, Yufang2; Tan, Shaoying2; Kuang, Dong2
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| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
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| 出版日期 | 2011-06-09 |
| 卷号 | 54期号:11页码:3732-3745 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/jm200258t |
| 文献子类 | Article |
| 英文摘要 | A novel series of acenaphtho[1,2-b]pyrrole derivatives as potent and selective inhibitors of fibroblast growth factor receptor 1 (FGFR1) were designed and synthesized. In silico target prediction revealed that tyrosine kinases might be the potential targets of the representative compound 2, which was subsequently validated by enzyme linked immunosorbent assay (ELISA) for its selective and active FGFR1 inhibition of various tyrosine kinases. The structure activity relationship (SAR) analysis aided by molecular docking simulation in the ATP binding site demonstrated that acenaphtho[1,2-b]pyrrole carboxylic acid esters (2-5) are potent inhibitors of FGFR1 with IC50 values ranging from 19 to 77 nM. Furthermore, these compounds exhibited favorable growth inhibition property against FGFR-expressing cancer cell lines with IC50 values ranging from micromolar to submicromolar. Western blotting analysis showed that compounds 2, 3, and 2b inhibited activation of FGFR1 and extracellular-signal regulated kinase 1/2 (Erk1/2). |
| WOS关键词 | TYROSINE KINASE INHIBITORS ; MEDICINAL CHEMISTRY ; TUMOR-CELLS ; ANTITUMOR EVALUATION ; ANTICANCER AGENTS ; TOPOISOMERASE-II ; CANCER ; DISCOVERY ; APOPTOSIS ; FLUORESCENCE |
| 资助项目 | Key New Drug Creation and Manufacturing Program[2009ZX09103-001] ; Key New Drug Creation and Manufacturing Program[2009ZX09103-102] ; National High Technology Research and Development Program of China (863 Program)[2011AA10A207] ; China 111 Project[B07023] ; Shanghai Leading Academic Discipline Project[B507] ; Fundamental Research Funds for the Central Universities[00000000] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000291082500004 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278503]  |
| 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 |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China; 2.E China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China |
| 推荐引用方式 GB/T 7714 | Chen, Zhuo,Wang, Xin,Zhu, Weiping,et al. Acenaphtho[1,2-b]pyrrole-Based Selective Fibroblast Growth Factor Receptors 1 (FGFR1) Inhibitors: Design, Synthesis, and Biological Activity[J]. JOURNAL OF MEDICINAL CHEMISTRY,2011,54(11):3732-3745. |
| APA | Chen, Zhuo.,Wang, Xin.,Zhu, Weiping.,Cao, Xianwen.,Tong, Linjiang.,...&Qian, Xuhong.(2011).Acenaphtho[1,2-b]pyrrole-Based Selective Fibroblast Growth Factor Receptors 1 (FGFR1) Inhibitors: Design, Synthesis, and Biological Activity.JOURNAL OF MEDICINAL CHEMISTRY,54(11),3732-3745. |
| MLA | Chen, Zhuo,et al."Acenaphtho[1,2-b]pyrrole-Based Selective Fibroblast Growth Factor Receptors 1 (FGFR1) Inhibitors: Design, Synthesis, and Biological Activity".JOURNAL OF MEDICINAL CHEMISTRY 54.11(2011):3732-3745. |
入库方式： OAI收割
来源：上海药物研究所
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