Abstract
The discovery of the importance of kinase activity and its relationship to the emergence and proliferation of cancer cells, due to changes in normal physiology, opened a remarkable pathway for the treatment of chronic myelogenous leukemia through intense search of drug candidates. Six Abl kinase inhibitors have received the US FDA approval as chronic myelogenous leukemia treatment, and continuous efforts in obtaining new, more effective and selective molecules are being carried out. Herein we discuss the mechanisms of Abl inhibition, structural features and ligand/protein interactions that are important for the design of new Abl kinase inhibitors. This review provides a broad overview of binding mode predictions, through molecular docking, which can be an approach to discover novel Abl kinase inhibitors.
Disclosure
Chemical structures were prepared using ChemDraw Standard 12.0 and Chem3D Ultra 9.0. Biological structures were prepared through open-source molecular visualization system PyMOL (DeLano, W. L. The PyMOL Molecular Graphics System [2002] on the web at www.pymol.org/), using crystallographic complexes data from Protein Data Bank (www.rcsb.org/pdb/home/home.do).
Financial & competing interests disclosure
Grant support: Foundation of Research Support and Innovation of Espirito Santo – FAPES and Federal University of Espirito Santo – UFES. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.