Inhibitors of the Ras Superfamily G-proteins, Part B, Volume 34

• 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

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.

• Informs and updates on all the latest developments in the field
• Contributions from leading authorities and industry experts

Researchers in biochemistry, molecular and cell biology, pharmacology, and cancer