Contents

Preface v

Contributors xi

1. Protein Tyrosine Kinases as Targets for Cancer and Other Indications 1

Mark Pearson, Carlos García-Echeverría, and Doriano Fabbro

2. Inhibitors of Signaling Interfaces: Targeting Src Homology 2

Domains in Drug Discovery 31

Carlos García-Echeverría

3. PI3-Kinase Inhibition: A Target for Therapeutic Intervention 53

Peter M. Finan and Stephen G. Ward

4. Src as a Target for Pharmaceutical Intervention:

Potential and Limitations 71

Mira Susa, Martin Missbach, Rainer Gamse, Michaela Kneissel,

Thomas Buhl, Jürg A. Gasser, Markus Glatt, Terence O'Reilly,

Anna Teti, and Jonathan Green

5. Activated FLT3 Receptor Tyrosine Kinase as a Therapeutic Target in Leukemia 93

Blanca Scheijen and James D. Griffin

6. JAK Kinases in Leukemias, Lymphomas, and Multiple Myeloma ...115 Renate Burger and Martin Gramatzki

A Targeted Therapy for Chronic Myelogenous Leukemia 145

Elisabeth Buchdunger and Renaud Capedeville

8. Platelet-Derived Growth Factor: Normal Function, Role in Disease, and Application of PDGF Antagonists 161

Tobias Sjöblom, Kristian Pietras, Arne Östman, and Carl-Henrik Heldin

9. Structural Biology of Protein Tyrosine Kinases 187

Sandra W. Cowan-Jacob, Paul Ramage, Wilhelm Stark,

Gabriele Fendrich, and Wolfgang Jahnke

10. Testing of Signal Transduction Inhibitors in Animal Models of Cancer 231

Terence O'Reilly and Robert Cozens x

Contents

11. Phosphoproteomics in Drug Discovery and Development 265

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, Jennifer A. Caldwell-Busby, and David R. Stover

Index

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