Recent Advances in Discovery of New Tyrosine Kinase Inhibitors Using Computational Methods

Tyrosine kinases are enzymes that phosphorylate tyrosine residues in specific substrates, and their activities are involved in the pathophysiology of cancer. The inhibitors of tyrosine kinases block their oncogenic activation in cancer cells, therefore presenting a target for the development of new anticancer drugs. The computational methods in drug discovery and development minimize the time and cost needed in drug designing process. We have reviewed the recent advance in the quantitative structure-activity relationship (QSAR) study and molecular docking related to the new antitumor agents, such as amidine derivatives of 3,4-ethylenedioxythiophene, quinoline-arylamidine hybrids, 7-chloro-4-aminoquinoline-benzimidazole hybrids, rhodanine derivatives, and flavonoids isolated from the leaves of Cupressus sempervirens. The QSAR studies revealed important physicochemical and structural requirements for the antitumor activity and generated models for the prediction of antitumor activity of future potent molecules. Molecular docking allows rapid screening of a large number of compounds to determinate of potential binders of the target protein or enzyme, which is related to the anticancer activity and possible mechanism of action.