首页>>文献首页>>文献正文

Acenaphtho[1,2-b]pyrrole-Based Selective Fibroblast Growth Factor Receptors 1 (FGFR1) Inhibitors: Design, Synthesis, and Biological Activity

meijin 添加于 2011/6/17 14:22:14  1906次阅读 | 0次推荐 | 0个评论

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 (E...

作 者:Zhuo Chen†‡, Xin Wang†, Weiping Zhu†, Xianwen Cao†, Linjiang Tong‡, Honglin Li†, Hua Xie*‡, Yufang Xu*†, Shaoying Tan†, Dong Kuang†, Jian Ding‡, and Xuhong Qian*†
期刊名称: American Chemical Society
期卷页: 第卷 第期 ~页
学科领域:生命科学 » 生物物理、生物化学与分子生物学 » 生物化学
添加人是否为作者:
原文链接:http://pubs.acs.org/doi/abs/10.1021/jm200258t?prevSearch=%28Acenaphtho%5B1%2C2-b%5Dpyrrole-Based+Selective+Fibroblast+Growth+Factor+Receptors+1+%28FGFR1%29+Inhibitors%3A+Design%2C+Synthesis%2C+and+Biological+Activity%29+NOT+%5Batype%3A+ad%5D+NOT+%5Batype%
DOI:
ISBN:
关键词:
相关报道: http://paper.sciencenet.cn/htmlpaper/201161714233486817522.shtm
备 注:
文献笔记

   
导出选项:

评论 (0 个评论)

Page 1 of 1
<<<[1]>>>

举报 | Archiver | 科学网( 京ICP备07017567 )

GMT+8, 2011-2-15 11:31

Powered by ScienceNet.cn

Copyright © 2007- 科学时报社