Protein Tyrosine Kinases

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September 2005



Leading researchers, from the Novartis group that pioneered Gleevec/Glivec(TM) and around the world, comprehensively survey the state of the art in the drug discovery processes (bio- and chemoinformatics, structural biology, profiling, generation of resistance, etc.) aimed at generating PTK inhibitors for the treatment of various diseases, including cancer. Highlights include a discussion of the rationale and the progress made towards generating "selective" low molecular-weight kinase inhibitors; an analysis of the normal function, role in disease, and application of platelet-derived growth factor antagonists; and a summary of the factors involved in successful structure-based drug design. Additional chapters address the advantages and disadvantages of in vivo preclinical models for testing protein kinase inhibitors with antitumor activity and the utility of different methods in the drug discovery and development process for determining "on-target" vs "off-target" effects of kinase inhibitors.


Protein Tyrosine Kinases as Targets for Cancer and Other Indications
Mark Pearson, Carlos García-Echeverría, and Doriano Fabbro

Inhibitors of Signaling Interfaces: Targeting Src Homology 2 Domains in Drug Discovery
Carlos García-Echeverría

PI3-Kinase Inhibition: A Target for Therapeutic Intervention
Peter M. Finan and Stephen G. Ward

Src as a Target for Pharmaceutical Intervention: Potential and Limitations
Mira Susa, Martin Missbach, Rainer Gamse, Michaela Kneissel, Thomas Buhl, Jürg A. Gasser, Markus Glatt, Terence O'Reilly, Anna Teti, and Jonathan Green

Activated FLT3 Receptor Tyrosine Kinase as a Therapeutic Target in Leukemia
Blanca Scheijen and James D. Griffin

JAK Kinases in Leukemias, Lymphomas, and Multiple Myeloma
Renate Burger and Martin Gramatzki

Glivec® (Gleevec®, Imatinib, STI571): A Targeted Therapy for Chronic Myelogenous Leukemia
Elisabeth Buchdunger and Renaud Capedeville

Platelet-Derived Growth Factor: Normal Function, Role in Disease, and Application of PDGF Antagonists
Tobias Sjöblom, Kristian Pietras, Arne Östman, and Carl-Henrik Heldin

Structural Biology of Protein Tyrosine Kinases
Sandra W. Cowan-Jacob, Paul Ramage, Wilhelm Stark, Gabriele Fendrich, and Wolfgang Jahnke

Testing of Signal Transduction Inhibitors in Animal Models of Cancer
Terence O'Reilly and Robert Cozens

Phosphoproteomics in Drug Discovery and Development
Michel F. Moran, Jarrod A. Marto, Cynthia J. Brame, Olga Ornatsky, Mark M. Ross, Leticia M. Toledo-Sherman, Alfredo C. Castro, Brett Larsen, Henry Duewel, Christopher Hosfield, Christopher Orsi, Thodoros Topaloglou, Daniel Figeys, Jarrod A. Caldwell-Busby, and David R. Stover

EAN: 9781588293848
ISBN: 158829384X
Untertitel: From Inhibitors to Useful Drugs. 'Cancer Drug Discovery and Development'. Bibliographie. Book. Sprache: Englisch.
Verlag: Springer-Verlag GmbH
Erscheinungsdatum: September 2005
Seitenanzahl: xiii
Format: gebunden
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