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Design of chimeric histone deacetylase- and tyrosine kinase-inhibitors: a series of imatinib hybrides as potent inhibitors of wild-type and mutant BCR-ABL, PDGF-Rbeta, and histone deacetylases.

Mahboobi, Siavosh ; Dove, Stefan ; Sellmer, Andreas ; Winkler, Matthias ; Eichhorn, Emerich ; Pongratz, Herwig ; Ciossek, Thomas ; Baer, Thomas ; Maier, Thomas ; Beckers, Thomas


Inhibitors of histone deacetylases are a new class of cancer therapeutics with possibly broad applicability. Combinations of HDAC inhibitors with the kinase inhibitor 1 (Imatinib) in recent studies showed additive and synergistic effects. Here we present a new concept by combining inhibition of protein kinases and HDACs, two independent pharmacological activities, in one synthetic small molecule. ...


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