Optimization of novel combi-molecules: Identification of balanced and mixed bcr-abl/DNA targeting properties

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.

Graphical abstractWe designed and synthesized an optimized combi-molecule that induced approximately twofold stronger abl TK inhibitory activity than Gleevec and high levels of DNA damage in chronic myelogenous leukemic cells (CML).Figure optionsDownload full-size imageDownload as PowerPoint slide