Inhibitors of the Ras Superfamily G-proteins, Part B

1st Edition - November 7, 2013

Editors: Fuyuhiko Tamanoi, Channing J. Der

Hardback ISBN:

9 7 8 - 0 - 1 2 - 4 2 0 1 4 6 - 0

eBook ISBN:

9 7 8 - 0 - 1 2 - 4 2 0 2 1 1 - 5

Targeted toward researchers in biochemistry, molecular and cell biology, pharmacology, and cancer, this is the second part of The Enzymes' volumes that discuss inhibitors of the… Read more

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Targeted toward researchers in biochemistry, molecular and cell biology, pharmacology, and cancer, this is the second part of The Enzymes' volumes that discuss inhibitors of the Ras superfamily G-proteins.

Preface
Chapter One. Discovery of Small-Molecule Ras Inhibitors that Display Antitumor Activity by Interfering with Ras·GTP–Effector Interaction

Abstract
1 Introduction
2 Discovery of Surface Pockets in Novel Crystal Structures of Ras·GTP
3 Discovery of the Kobe0065-Family Compounds by In Silico Screening
4 Inhibition of Ras Functions by the Kobe0065-Family Compounds
5 Structural Basis for Inhibition of Ras Functions by the Kobe0065-Family Compounds
6 Specificity of the Kobe0065-Family Compounds Toward Various Small GTPases
7 Discussion and Conclusion
Acknowledgments
References

Chapter Two. An Orthosteric Inhibitor of the RAS–SOS Interaction

Abstract
1 Introduction
2 RAS Signaling in Normal Physiology and Malignancy
3 Strategies for Targeting RAS Activity
4 Inhibitor Design
5 RAS Binding
6 Cell Entry and Intracellular Effects
7 Conclusions
References

Chapter Three. Conformation-Specific Inhibitors of Raf Kinases

Abstract
1 Introduction
2 Kinase Conformations and Different Types of Kinase Inhibitors
3 Representative Raf Inhibitors and Their Binding Modes
4 Raf Kinase Dimerization and Activation
5 Perspective
6 Conclusion
Acknowledgments
References

Chapter Four. Inhibitors of the ERK Mitogen-Activated Protein Kinase Cascade for Targeting RAS Mutant Cancers

Abstract
1 Introduction
2 Ras and the ERK MAPK Effector Signaling Network
3 Role of the ERK MAPK Cascade in Mutant RAS-Dependent Tumor Progression and Maintenance
4 MEK1/2 Inhibitors
5 ERK1/2 Inhibitors
6 Issues and Questions
Acknowledgments
References

Chapter Five. Inhibiting the RAS–PI3K Pathway in Cancer Therapy

Abstract
1 Introduction
2 The PI3K Pathway
3 PI3K Inhibitors
4 PI3K Pathway Inhibitors
5 Inhibiting PI3K in Cancer
6 Future Directions
References

Chapter Six. The RalGEF/Ral Pathway: Evaluating an Intervention Opportunity for Ras Cancers

Abstract
1 Introduction
2 RalGEF/Ral Signaling and Cancer: A Rationale for Pathway Inhibition
3 Modes of RalGEF/Ral Pathway Inhibition
4 Conclusion
Acknowledgments
References

Chapter Seven. p21-Activated Kinase Inhibitors

Abstract
1 Introduction
2 ATP-competitive PAK Inhibitors
3 Allosteric PAK Inhibitors
4 Conclusions and Outlook
References

Chapter Eight. Recent Progress in Developing Small Molecule Inhibitors Designed to Interfere with Ras Membrane Association: Toward Inhibiting K-Ras and N-Ras Functions

Abstract
1 Introduction
2 Combined Inhibition of FTase and GGTase-I to Inhibit K-Ras and N-Ras
3 ICMT Inhibitors
4 Inhibiting the Interaction of K-Ras and PDEδ
5 Future Prospects
Acknowledgments
References

Chapter Nine. Synthetic Lethal Genetic Screens in Ras Mutant Cancers

Abstract
1 Introduction
2 Synthetic Lethality and Its Application in Cancer Research
3 Synthetic Lethality Screen to Find “Achilles’ Heel” of Ras Mutant Cancers
4 Conclusion and Perspectives
Acknowledgments
References

Author Index
Subject Index