Kinase Inhibitors Methods and Protocols

Protein and lipid kinases are often the master regulators of cell signaling in eukaryotic systems. The human genome codes for more than 500 of these enzymes and their misregulation has been shown to be involved in the onset and progression of many disease

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MOLECULAR BIOLOGY™

Series Editor John M. Walker School of Life Sciences University of Hertfordshire Hatfield, Hertfordshire, AL10 9AB, UK

For further volumes: http://www.springer.com/series/7651

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Kinase Inhibitors Methods and Protocols

Edited by

Bernhard Kuster LS für Proteomik und Bioanalytik, Technische Universität München, Freising, Germany

Editor Bernhard Kuster LS für Proteomik und Bioanalytik Technische Universität München Emil Erlenmeyer Forum 5 85354 Freising Germany [email protected]

ISSN 1064-3745 e-ISSN 1940-6029 ISBN 978-1-61779-336-3 e-ISBN 978-1-61779-337-0 DOI 10.1007/978-1-61779-337-0 Springer New York Dordrecht Heidelberg London Library of Congress Control Number: 2011936748 © Springer Science+Business Media, LLC 2012 All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Humana Press, c/o Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights. Printed on acid-free paper Humana Press is part of Springer Science+Business Media (www.springer.com)

Preface Protein and lipid kinases are often the master regulators of cell signaling in eukaryotic systems. The human genome codes for more than 500 of these enzymes and their misregulation has been shown to be involved in the onset and progression of many diseases including cancer and inflammation. Therefore, small molecule kinase inhibitors have become important research tools for the elucidation of many biological roles of kinases and their mechanisms of action. In addition, kinase inhibitors are now successful drugs in a number of liquid and solid tumors. In fact, about one dozen molecules are currently approved for clinical use and 200 more molecules are in different stages of clinical evaluation. Kinase inhibitors thus contribute significantly to the drug pipelines of pharmaceutical and biotechnology industries and to the growing need for the treatment of cancer and inflammation. There are many challenges in the discovery and development of kinase inhibitors both for research and clinical use and thus, many methods are being devised and applied to understand the often complex functional relationships between kinases and the respective inhibitors. In this book, experts in kinase biology, drug discovery, and clinical research present a series of exemplary methods that can be used to address these challenges. To set the scene, two introductory reviews discuss how kinase inhibitors can be used to target cancer and inflammation.