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E-raamat: Targeting Protein Kinases for Cancer Therapy

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  • Ilmumisaeg: 20-Sep-2011
  • Kirjastus: John Wiley & Sons Inc
  • Keel: eng
  • ISBN-13: 9781118210772
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  • Formaat: EPUB+DRM
  • Ilmumisaeg: 20-Sep-2011
  • Kirjastus: John Wiley & Sons Inc
  • Keel: eng
  • ISBN-13: 9781118210772
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An expert guide to targeting protein kinases in cancer therapy Research has shown that protein kinases can instigate the formation and spread of cancer when they transmit faulty signals inside cells. Because of this fact, pharmaceutical scientists have targeted kinases for intensive study, and have been working to develop medicinal roadblocks to sever their malignant means of communication.

Complete with full-color presentations, Targeting Protein Kinases for Cancer Therapy defines the structural features of protein kinases and examines their cellular functions. Combining kinase biology with chemistry and pharmacology applications, this book enlists emerging data to drive the discovery of new cancer-fighting drugs. Valuable information includes:





Comprehensive overviews of the major kinase families involved in oncology, integrating protein structure and function, and providing important tools to assist pharmaceutical researchers to understand and work in this dynamic area of cancer drug research



Focus on small molecule inhibitors as well as other therapeutic modalities



Discussion of kinase inhibitors that have entered clinical trials for the treatment of cancer, with an emphasis on molecules that have progressed to late stage clinical trials and, in a few cases, to market





Providing a platform for further study, this important work reviews both the successes and challenges of kinase inhibitor therapy, and provides insight into future directions in the war against cancer.

Arvustused

"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)

Muu info

Winner of PROSE (Biomedicine/Neuroscience) 2010.
Preface xi
Acknowledgments xiii
Kinases and Cancer
1(74)
A Brief History of Protein Phosphorylation
1(2)
Kinases and Cancer
3(5)
A Tour of the Human Protein Kinase Superfamily
8(38)
Tyrosine Kinase Group
12(10)
TKL (Tyrosine Kinase-like) Group
22(3)
STE Group
25(2)
CSNK1 Group
27(1)
AGC Group
28(2)
CAMK Group
30(2)
CMGC Group
32(4)
RGC Group
36(1)
Others
36(5)
Atypical Protein Kinases
41(1)
Nonprotein Kinases
41(5)
Strategic Considerations for Selecting Kinases as Drug Targets
46(5)
Comparison of Kinase Inhibitor Therapeutic Strategies
51(7)
Small Molecule Versus Antibody-Directed Therapies
51(1)
Alternative Strategies for Kinase Inhibition
51(7)
References
58(17)
Protein Kinase Structure, Function, and Regulation
75(44)
Ligand Binding to Receptor Tyrosine Kinases
76(7)
EGF: EGF Receptor Interactions
76(2)
Insulin: Insulin Receptor and IGF1: IGF1R
78(1)
FGF: FGF Receptor (Heparin/Heparan Sulfate) Interactions
79(1)
VEGF: VEGF Receptor Interactions
80(1)
Angiopoietin2: TIE2 Receptor Interactions
80(2)
Ephrin: EPH Receptor Interactions
82(1)
The Role of Transmembrane Domains
82(1)
Protein Kinase Domain Structure and Function
83(4)
Catalytic Activity of Protein Kinases
87(4)
Steady State Kinetics
87(2)
Chemistry of Protein Kinase Catalysis
89(2)
Protein Kinase Regulation
91(16)
Regulation Via Activation Segment Phosphorylation
92(4)
Regulation by N-Terminal Sequences and Domains
96(2)
C-Terminal Regulatory Regions
98(4)
Regulation by Other Domains and Partner Proteins
102(5)
References
107(12)
Receptor Tyrosine Kinases
119(96)
EGF/ERBB Receptors
120(10)
ERBB Receptors and Cancer
128(2)
Insulin/IGF Receptors
130(6)
Insulin/IGF Receptors and Cancer
134(2)
Anaplastic Lymphoma Kinase
136(4)
ALK and Cancer
137(3)
VEGF Receptors (VEGFR1, VEGFR2, VEGFR3)
140(6)
PDGF Receptors
146(7)
PDGFRs and Cancer
149(4)
FGF Receptors
153(5)
FGFRs and Cancer
156(2)
KIT
158(7)
KIT and Cancer
160(5)
FLT3
165(3)
FLT3 and Cancer
167(1)
RET
168(2)
RET and Thyroid Carcinoma
169(1)
MET and RON
170(7)
MET
170(5)
RON
175(2)
References
177(38)
Nonreceptor Tyrosine Kinases
215(50)
ABL
216(7)
ARG
223(1)
SRC and SRC Family Kinases
224(11)
SRC
228(4)
Cellular Roles of SRC
232(2)
SRC and Cancer
234(1)
FAK
235(3)
FAK and Cancer
238(1)
JAK2
238(8)
Activation and Known Mutations and Fusions of the JAK Family of Tyrosine Kinases
241(2)
Further Roles of JAK2 in Tumor Growth
243(3)
References
246(19)
Intracellular Signal Transduction Cascades
265(62)
The PI3K/PTEN Pathway
266(13)
PI3K
267(3)
PDK1
270(1)
AKT
271(2)
Other AGC Kinases
273(2)
PI3K Pathway Activation in Cancer
275(4)
mTOR Signaling
279(5)
mTOR
279(3)
p70S6 Kinase
282(1)
mTOR Pathway Activation in Cancer
283(1)
MAPK Signaling Pathways
284(9)
ERK/MAPK Signaling
285(1)
RAF Family Kinases
286(3)
MEK and ERK Kinases
289(2)
ERK/MAPK Pathway Activation in Cancer
291(2)
PIM Kinases
293(1)
Protein Kinase C
294(7)
PKC Activation
295(3)
Classical PKCs
298(1)
Novel PKCs
299(1)
Atypical PKCs
300(1)
References
301(26)
Cell Cycle Control
327(64)
Cyclin-Dependent Kinases (CDKs) and Cell Cycle Progression
327(15)
Introduction
328(4)
CDK4 and CDK6
332(2)
CDK2
334(3)
CDK3
337(1)
CDK1
337(4)
CDK10
341(1)
CCRK/CDCH/p42
341(1)
CDKs and mRNA Production
342(10)
Introduction
342(2)
CDK7
344(2)
CDK8
346(1)
CDK9
347(2)
CDK11
349(1)
CDK12 (CDC2-Related Kinase CRKRS)
350(1)
CDK13 (CDC2L5)
351(1)
Other CDK-Related Kinases
352(2)
CDK5
352(1)
GAK
353(1)
Mitotic Kinases
354(7)
PLKs
356(3)
Aurora Kinases
359(2)
Cell Cycle Checkpoint Kinases
361(7)
ATM, ATR, and DNAPK
362(2)
CHK1, CHK2, and MAPKAPK2
364(4)
References
368(23)
Structural Biochemistry of Kinase Inhibitors
391(44)
Strategies for Inhibitor Design
392(4)
Targeting the Active Versus Inactive Form
392(1)
ATP-Competitive Versus Noncompetitive Inhibitors
393(1)
Specific Versus Multitargeted Inhibitors
394(2)
Architecture of the ATP Binding Site: DFG-in
396(3)
Case Study: Inhibitors of CHK1
399(8)
Case Study: Inhibitors of CDK2
407(6)
Case Study: Inhibitors of SRC Family Kinases
413(3)
Case Study: EGF Receptor Inhibitors
416(4)
Targeting the Inactive Conformation
420(4)
Binding Mode of Imatinib
421(2)
Binding of BAY-43-9006 (Sorafenib) to the Inactive BRAF Kinase
423(1)
Noncompetitive Inhibition
424(2)
Kinase Inhibitor Specificity
426(3)
References
429(6)
Tyrosine Kinase Inhibitors
435(92)
BCR-ABL Inhibitors
435(11)
SRC Inhibitors
446(2)
JAK2 Inhibitors
448(4)
EGFR/ERBB Inhibitors
452(18)
Determinants of Response and Resistance to ERBB Inhibitors
455(15)
IGF1R Inhibitors
470(2)
FLT3 Inhibitors
472(8)
KIT Inhibitors
480(10)
MET/RON Inhibitors
490(6)
RET Inhibitors
496(2)
Other Inhibitors
498(2)
FAK
498(1)
TGFβ Receptor
499(1)
References
500(27)
Angiokinase Inhibitors
527(40)
Introduction
527(3)
Angiokinase Inhibitors
530(25)
References
555(12)
Intracellular Signaling Kinase Inhibitors
567(56)
mTOR Inhibitors
567(11)
Clinical Pharmacodynamics and Tolerability of mTOR Inhibitors
569(9)
PI3K Inhibitors
578(4)
RAF Kinase Inhibitors
582(2)
MEK Inhibitors
584(3)
CDK Inhibitors
587(6)
Cell Cycle Checkpoint Kinase Inhibitors
593(4)
Mitotic Kinase Inhibitors
597(7)
PLK Inhibitors
597(2)
Aurora Kinase Inhibitors
599(5)
Protein Kinase C Inhibitors
604(1)
References
605(18)
Current Challenges and Future Directions
623(42)
Kinase Inhibitor Drug Resistance
623(12)
Efflux Pumps and Drug Transporters
626(1)
Other DMPK Factors
627(1)
Target Mutation
628(3)
Target Overexpression and Activation
631(1)
Downstream Pathway Activation
632(1)
Redundant Receptors/Pathways
633(2)
Combination Therapy With Kinase Inhibitors
635(6)
Angiogenesis Inhibitors and Chemotherapy
637(1)
Survival Pathway Inhibitors and Chemotherapy/Targeted Therapy
638(1)
DNA Damage Checkpoint Inhibitors and Chemotherapy
639(1)
RTK Switching: Targeting Receptor Redundancy
640(1)
Systems Biology and Translational Medicine
641(11)
Classification of Tumors and Prediction of Response: Expression Profiling
642(3)
Phosphoprotein Analysis, Kinomics, and Systems-Based Approaches
645(2)
Translational Medicine
647(5)
Conclusions
652(1)
References
653(12)
List of Abbreviations 665(24)
Index 689
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.