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.
Rachid
Zakaria
Z
Cancer 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.
Katsoulas
Athanasia
A
Williams
Christopher
C
Larroque
Anne-Laure
AL
McNamee
James
J
Jean-Claude
Bertrand J
BJ
D045744:Cell Line, Tumor; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D004249:DNA Damage; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular
D004247:DNA; D016044:Fusion Proteins, bcr-abl