Abstract
Protein kinases are involved in many diseases like cancer, inflammation, cardiovascular disease, and diabetes. They have become attractive target classes for drug development, making kinase inhibitors as important class of therapeutics. The success of smallmolecule ATP-competitive kinase inhibitors such as Gleevec, Iressa, and Tarceva has attracted much attention in the recent past. Kinases make use of ATP for phosphorylation of a specific residue(s) on their protein substrates. More than 400 X-ray structures of about 70 different kinases are publicly available. These structures provide insights into selectivity and mechanisms of inhibition. However, prediction of binding specificity of kinase inhibitors based on structural information alone appears to be insufficient. Here, we will review these observations to gain insights into the rules that govern protein kinase inhibitor selectivity.
Keywords: Protein kinases, kinase domain, protein kinase conformation, DFG motif, kinase inhibitors, ATP-competitive inhibitors, kinase inhibitor selectivity
Current Pharmaceutical Design
Title: Protein Kinase Inhibitors: Structural Insights Into Selectivity
Volume: 13 Issue: 27
Author(s): Ram Thaimattam, Rahul Banerjee, Rajni Miglani and Javed Iqbal
Affiliation:
Keywords: Protein kinases, kinase domain, protein kinase conformation, DFG motif, kinase inhibitors, ATP-competitive inhibitors, kinase inhibitor selectivity
Abstract: Protein kinases are involved in many diseases like cancer, inflammation, cardiovascular disease, and diabetes. They have become attractive target classes for drug development, making kinase inhibitors as important class of therapeutics. The success of smallmolecule ATP-competitive kinase inhibitors such as Gleevec, Iressa, and Tarceva has attracted much attention in the recent past. Kinases make use of ATP for phosphorylation of a specific residue(s) on their protein substrates. More than 400 X-ray structures of about 70 different kinases are publicly available. These structures provide insights into selectivity and mechanisms of inhibition. However, prediction of binding specificity of kinase inhibitors based on structural information alone appears to be insufficient. Here, we will review these observations to gain insights into the rules that govern protein kinase inhibitor selectivity.
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Cite this article as:
Thaimattam Ram, Banerjee Rahul, Miglani Rajni and Iqbal Javed, Protein Kinase Inhibitors: Structural Insights Into Selectivity, Current Pharmaceutical Design 2007; 13 (27) . https://dx.doi.org/10.2174/138161207781757042
DOI https://dx.doi.org/10.2174/138161207781757042 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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