Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.
Skip to main content

© The Royal Society of Chemistry 2017. Protein kinases have developed into a major target family for the development of novel therapeutics. With currently more than 30 approved drugs and several hundred ongoing clinical studies, the kinase family has emerged as one of the most successful and established target families. The high degree of structural plasticity of the kinase catalytic domain revealed a multitude of diverse and sometimes target-specific cavities and binding modes, which has enabled the development of highly specific inhibitors. However, recent studies revealed additional essential non-catalytic functions of protein kinases usually associated with the kinase active state. Thus, allosteric kinase inhibitors that stabilize a variety of kinase inactive states modulating both catalytic as well as non-catalytic kinase functions, result in different cellular responses and clinical outcomes when compared with ATP competitive inhibitors that target the active state. These findings indicate that allosteric inhibitors could also be developed targeting scaffolding functions of catalytically inert pseudokinases that often play key roles in disease development. Here we review the main inhibitor classes that have been developed to date and the structural and functional consequences of their distinct binding modes to the kinase catalytic domain.

Original publication

DOI

10.1039/9781782629276-00040

Type

Chapter

Book title

RSC Drug Discovery Series

Publication Date

01/01/2017

Volume

2017-January

Pages

40 - 64