Development of a chimeric c-Src kinase and HDAC inhibitor.

Development of a chimeric c-Src kinase and HDAC inhibitor.
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DOI:
10.1021/ml400175d
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发表时间:
2013-08-08
影响因子:
4.2
通讯作者:
Soellner, Matthew B.
Soellner, Matthew B.
中科院分区:
医学3区
文献类型:
--
作者:
Ko, Kristin S.;Steffey, Michael E.;Brandvold, Kristoffer R.;Soellner, Matthew B.

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基于在选择性c-Src激酶抑制剂与HDAC抑制剂之间观察到的协同作用,描述了第一嵌合c-Src激酶和HDAC抑制剂的开发。优化的嵌合抑制剂显示为有效的c-Src和HDAC抑制剂。嵌合抑制剂4进一步显示在癌细胞系中高度有效,并且比使用离散的c-Src和HDAC抑制剂的双重靶向策略显著更有效。
On the basis of synergism observed between a selective c-Src kinase inhibitor with an HDAC inhibitor, the development of the first chimeric c-Src kinase and HDAC inhibitor is described. The optimized chimeric inhibitor is shown to be a potent c-Src and HDAC inhibitor. Chimeric inhibitor 4 is further shown to be highly efficacious in cancer cell lines and significantly more efficacious than a dual-targeting strategy using discrete c-Src and HDAC inhibitors.
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