Ulteriori informazioni
Informationen zum Autor DAVID J. MATTHEWS is Executive Director of Oncology Discovery at Exelixis, where he is responsible for cancer drug discovery. For more than fifteen years, Dr. Matthews has been involved in drug discovery projects in industry, with particular focus on small molecule inhibitors. He has twenty scientific publications and multiple patents to his credit. MARY E. GERRITSEN is Vice President of Molecular and Cellular Pharmacology at Exelixis, where she is in charge of cell-based screening in preclinical research and of biomarker studies for clinical development compounds in Phase I and II studies. Her prior industry experience includes positions at Genentech, Bayer and Millennium Pharmaceuticals. She has authored more than one hundred peer-reviewed articles and twenty-six book chapters and is an inventor on forty-two issued patents. Klappentext This book provides an overview of different protein kinases - structure, function, regulation, and their role in cancer. It combines kinase biology with chemistry and pharmacology applications for discovery and development of cancer drugs. The text also describes existing and emerging kinase inhibitors, focusing mostly on small molecules but also alternative approaches like therapeutic antibodies. Provides an important resource that helps pharmaceutical researchers understand and work in this dynamic area of cancer drug research. Zusammenfassung This book provides an overview of different protein kinases structure, function, regulation, and their role in cancer. Itcombines kinase biology with chemistry and pharmacologyapplications for discovery and development of cancer drugs. Inhaltsverzeichnis Preface. Acknowledgments. 1 KINASES AND CANCER. 1.1 A Brief History of Protein Phosphorylation. 1.2 Kinases and Cancer. 1.3 A Tour of the Human Protein Kinase Superfamily. 1.3.1 Tyrosine Kinase Group. 1.3.2 TKL (Tyrosine Kinase-Like) Group. 1.3.3 STE Group. 1.3.4 CSNK1 Group. 1.3.5 AGC group. 1.3.6 CAMK Group. 1.3.7 CMGC Group. 1.3.8 RGC Group. 1.3.9 Others. 1.3.10 Atypical Protein Kinases. 1.3.11 Non-Protein Kinases. 1.4 Strategic Considerations for Selecting Kinases as Drug Targets. 1.5 Comparison of Kinase Inhibitor Therapeutic Strategies. 1.5.1 Small Molecule Versus Antibody-Directed Therapies. 1.5.2 Alternative Strategies for Kinase Inhibition. References. 2 PROTEIN KINASE STRUCTURE, FUNCTION AND REGULATION. 2.1 Ligand Binding to Receptor Tyrosine Kinases. 2.1.1 EGF:EGF Receptor Interactions. 2.1.2 Insulin:Insulin Receptor and IGF1:IGF1R. 2.1.3 FGF:FGF Receptor (Heparin/Heparan Sulphate) Interactions. 2.1.4 VEGF:VEGF Receptor Interactions. 2.1.5 Angiopoietin2:TIE2 Receptor Interactions. 2.1.6 Ephrin:EPH Receptor Interactions. 2.1.7 The Role of Transmembrane Domains. 2.2 Protein Kinase Domain Structure and Function. 2.3 Catalytic Activity of Protein Kinases. 2.3.1 Steady State Kinetics. 2.3.2 Chemistry of Protein Kinase Catalysis. 2.4 Protein Kinase Regulation. 2.4.1 Regulation Via Activation Segment Phosphorylation. 2.4.2 Regulation by N-terminal Sequences and Domains. 2.4.3 C-Terminal Regulatory Regions. 2.4.4 Regulation by Other Domains and Partner Proteins. References. 3 RECPETOR TYROSINE KINASES. 3.1 EGF/ERBB Receptors. 3.1.1 ERBB Receptors and Cancer. 3.2 Insulin/IGF Receptors. 3.2.1 Insulin/IGF Receptors and Cancer. 3.3 Anaplastic Lymphoma Kinase. 3.3.1 ALK and Cancer. 3.4 VEGF Receptors (VEGFR1, VEGFR2, VEGFR3). 3.5 PDGF Receptors. 3.5.1 PDGFRs and Cancer. 3.6 FGF Receptors. 3.6.1 FGFRs and Cancer. 3.7 KIT. ...
