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Optimization of novel combi-molecules: identification of balanced and mixed bcr-abl/DNA targeting properties
Zakaria Rachid1, Athanasia Katsoulas, Christopher Williams
1Cancer Drug Research Laboratory, Division of Medical Oncology, Department of Medicine, McGill University/Royal Victoria Hospital, 687 Pine Avenue West Rm. M-719, Montreal, Que., Canada H3A 1A1.
Abstract:
Steps toward the identification of combi-molecules with strong abl tyrosine kinase (TK) inhibitory property and significant DNA damaging potential are described. The optimized combi-molecule 13a was shown to induce approximately twofold stronger abl TK inhibitory activity than Gleevec and high levels of DNA damage in chronic myelogenous leukemic cells.
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