Small Molecules in Oncology
Extensive research into the molecular mechanisms of cancer disease has heralded a new age of targeted therapy. In malignant cells, key proteins that are crucial to tumor growth and survival are now being targeted directly with rationally designed inhibito
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Managing Editors
P. M. Schlag, Berlin
H.-J. Senn, St. Gallen
Associate Editors
P. Kleihues, Zürich F. Stiefel, Lausanne B. Groner, Frankfurt A. Wallgren, Göteborg Founding Editor
P. Rentchnik, Geneva
184
Uwe M. Martens (Ed.)
Small Molecules in Oncology
13
Editor Prof. Dr. Uwe M. Martens SLK-Kliniken Heilbronn GmbH Medizinische Klinik III Am Gesundbrunnen 20-26 74078 Heilbronn Germany Freiburg University Medical Center Department of Hematology and Oncology Hugstetterstraße 55 79106 Freiburg, Germany [email protected]
ISBN: 978-3-642-01221-1
e-ISBN: 978-3-642-01222-8
DOI: 10.1007/978-3-642-01222-8 Springer Heidelberg Dordrecht London New York Library of Congress Control Number: 2009933609 © Springer-Verlag Berlin Heidelberg 2010 This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer. Violations are liable to prosecution under the German Copyright Law. The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product liability: The publishers cannot guarantee the accuracy of any information about dosage and application contained in this book. In every individual case the user must check such information by consulting the relevant literature. Cover design: eStudioCalamar Figueres/Berlin Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com)
Contents
Part I 1
Protein Kinase Inhibitors
Imatinib Mesylate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Cornelius F. Waller 1.1 1.2 1.3 1.4 1.5 1.6 1.6.1 1.6.2 1.6.3 1.6.4 1.7 1.8 1.9 1.10 1.11
2
Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Chemical Structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Clinical Pharmacology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Drug Targets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Preclinical Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Clinical Data in CML . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Phase I Trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Phase II Studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Phase III Study (IRIS-Trial) . . . . . . . . . . . . . . . . . . .
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