Targeting Protein Kinases for Cancer Therapy

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. 3.7.1 KIT...

List of contents

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 vs. antibody-directed therapies.
 
1.5.2 Alternative strategies for kinase inhibition.
 
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.
 
3 Receptor 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 (ALK).
 
3.3.1 ALK and Cancer.
 
3.4 VEGF receptors (VEGFR1, VEGFR2, VEGFR3).
 
3.5 PDGF Receptors.
 
3.5.1 PDGF Receptors and Cancer.
 
3.6 FGF Receptors.
 
3.6.1 FGF Receptors and Cancer.
 
3.7 KIT.
 
3.7.1 KIT and Cancer.
 
3.8 FLT3.
 
3.8.1 FLT3 and Cancer.
 
3.9 RET.
 
3.9.1 RET and Thyroid Carcinoma.
 
3.10 MET (HGF receptor) and RON (MSP receptor).
 
3.10.1 MET.
 
3.10.2 RON.
 
4 Non-Receptor Tyrosine Kinases.
 
4.1 ABL.
 
4.2 ARG.
 
4.3 SRC and SRC family kinases.
 
4.3.1 SRC.
 
4.3.2 Cellular Roles of SRC.
 
4.3.3 SRC and Cancer.
 
4.4 FAK.
 
4.4.1 FAK and Cancer.
 
4.5 JAK2.
 
4.5.1 Activation and known mutations and fusions of the JAK family of tyrosine kinases.
 
4.5.2 Further roles of JAK2 in tumor growth.
 
5 Intracellular Signal Transduction Cascades.
 
5.1 The PI3K/PTEN Pathway.
 
5.1.1 PI-3 kinase.
 
5.1.2 PDK1.
 
5.1.3 AKT.
 
5.1.4 Other AGC kinases.
 
5.1.5 PI3K Pathway Activation in Cancer.
 
5.2 mTOR Signaling.
 
5.2.1 mTOR.
 
5.2.2 p70S6 Kinase.
 
5.2.3 mTOR Pathway Activation in Cancer.
 
5.3 MAPK signaling pathways.
 
5.3.1 ERK/MAPK signaling.
 
5.3.2 RAF family kinases.
 
5.3.2 MEK and ERK kinases.
 
5.3.3 ERK/MAPK Pathway Activation in Cancer.
 
5.4 PIM kinases.
 
5.5 Protein Kinase C.
 
5.5.1 PKC Activation.
 
5.5.2 Classical PKCs.
 
5.5.3 Novel

Report

"The comprehensive coverage makes the book highly recommendable for beginners and expert researchers in oncology and should be present on their shelves." ( ChemMedChem , November 2010)

Product details

• Authors: Mary E Gerritsen, Mary E. Gerritsen, Gerritsen Mary E., David Matthews, David J Matthews, David J. Matthews, David J. Gerritsen Matthews, Dj Matthews, Matthews David J.
• Publisher: Wiley, John and Sons Ltd
• Languages: English
• Product format: Hardback
• Released: 12.03.2010
• EAN: 9780470229651
• ISBN: 978-0-470-22965-1
• No. of pages: 702
• Dimensions: 159 mm x 235 mm x 44 mm
• Subjects: Natural sciences, medicine, IT, technology > Chemistry; Chemie, Medizin, Onkologie, Krebstherapie, Life Sciences, Biowissenschaften, chemistry, Wirkstoffforschung u. -entwicklung, Drug Discovery & Development, Medical Science, Onkologie u. Strahlentherapie, Oncology & Radiotherapy, Proteins & Macromolecules, Proteine u. Makromoleküle, Proteinkinase