Protein kinases have emerged as the most important class of targets in oncology drug discovery because of
their major roles in regulating cellular growth and survival. At least, 11 kinase inhibitors have received FDA approval to
be used as cancer treatments, and there are continuous efforts to bring more candidates from laboratory benches to the
clinic. Although many protein kinase inhibitors directly interact with the ATP binding site, other can alter the kinase
conformation to prevent productive ATP binding. Herein we discuss the different mechanisms of action of kinase
inhibitors and provide classification of the inhibitors according to their binding sites. Some of these are allosteric
inhibitors, ATP competitive inhibitors, protein substrate competitive inhibitors, and covalent bond forming inhibitors.
This review provides a broad overview of the relation between mechanism of action and the issues of target selectivity
and resistance. Special attention was given to the kinase inhibitors currently in clinical trials.
Keywords: Allosteric inhibitors, anti-cancer agents, antiproliferative activity, ATP competitive inhibitors, non-ATP
competitive inhibitors, protein kinase, target specificity
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