Abstract
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
Mini-Reviews in Medicinal Chemistry
Title:Small Molecule Kinase Inhibitors as Anti-Cancer Therapeutics
Volume: 12 Issue: 5
Author(s): O. Chahrour, D. Cairns and Z. Omran
Affiliation:
Keywords: Allosteric inhibitors, anti-cancer agents, antiproliferative activity, ATP competitive inhibitors, non-ATP competitive inhibitors, protein kinase, target specificity
Abstract: 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.
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Cite this article as:
Chahrour O., Cairns D. and Omran Z., Small Molecule Kinase Inhibitors as Anti-Cancer Therapeutics, Mini-Reviews in Medicinal Chemistry 2012; 12 (5) . https://dx.doi.org/10.2174/138955712800493915
DOI https://dx.doi.org/10.2174/138955712800493915 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
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