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

Bioorg Med Chem Lett. 2007 Aug 1;17(15):4248-53. doi: 10.1016/j.bmcl.2007.05.067. Epub 2007 May 24.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • DNA / drug effects*
  • DNA / metabolism
  • DNA Damage
  • Fusion Proteins, bcr-abl / metabolism*
  • Humans
  • Models, Molecular

Substances

  • DNA
  • Fusion Proteins, bcr-abl