Inhibitors of Protein Kinases and Protein Phosphates (eBook)

The Editor (L.A. Pinna) is full Professor of Medical Chemistry at the University of Padova since 1975. He has been involved for over 30 years in the study of various aspects of protein phosphorylation, with special reference to the analysis of consensus sequences of protein kinases and the development of peptide substrates for the specific monitoring of individual members of this family of enzymes. In this field he has published more than 290 original pepers and a number of review articles in international journals. Over the last years he has provided major contributions to the molecular and structural enzymology of protein kinases implicated in cell fate decision and in the development of inhibitors of one of these enzymes. The co-Editor (P.T.W. Cohen) is an authority in the field of protein phosphatases.

Preface 5
List of Contributors 7
List of Contents 8
Protein Kinase Inhibitors for the Treatment of Disease: The Promise and the Problems 10
General Aspects of PKs Inhibition 17
New Design Strategies for Ligands That Target Protein Kinase- Mediated Protein– Protein Interactions 18
Pharmacological Potential and Inhibitors of Individual Classes of Protein Kinases 52
The Paullones: A Family of Pharmacological Inhibitors of Cyclin- Dependent Kinases and Glycogen Synthase Kinase 3 53
Pharmacological Potential of p38 MAPK Inhibitors 71
Inhibitors of PKA and Related Protein Kinases 90
Inhibitors of Protein Kinase CK2: Structural Aspects 130
Aminoglycoside Kinases and Antibiotic Resistance 161
Pharmacological Potential and Inhibitors of Individual Classes of Protein Phosphatases 193
Protein Tyrosine Phosphatases as Therapeutic Targets 194
Structure-Based Design of Protein Tyrosine Phosphatase Inhibitors 218
Biological Validation of the CD45 Tyrosine Phosphatase as a Pharmaceutical Target 266
Serine/Threonine Protein Phosphatase Inhibitors with Antitumor Activity 297
Inhibitors in Clinical Use or Advanced Clinical Trials 320
Clinical Immunosuppression using the Calcineurin- Inhibitors Ciclosporin and Tacrolimus 321
Targeted Therapy with Imatinib: An Exception or a Rule? 360
Clinical Aspects of Imatinib Therapy 389
Isoquinolinesulfonamide: A Specific Inhibitor of Rho-Kinase and the Clinical Aspect of Anti- Rho-Kinase Therapy 409
Discovery and Development of Iressa: The First in a New Class of Drugs Targeted at the Epidermal Growth Factor Receptor Tyrosine Kinase 431
Subject Index 449