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ACS Med Chem Lett. 2013 Aug 8;4(8):779-783.

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

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Department of Chemistry, University of Michigan, 930 N. University Avenue, Ann Arbor, Michigan 48109, United States.


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.


HDAC; c-Src; chimera; combination therapy; kinase

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