COVID-19 Update: We are currently shipping orders daily. However, due to transit disruptions in some geographies, deliveries may be delayed. To provide all customers with timely access to content, we are offering 50% off Science and Technology Print & eBook bundle options. Terms & conditions.
Inhibitors of the Ras Superfamily G-proteins, Part A - 1st Edition - ISBN: 9780124167490, 9780124169678

Inhibitors of the Ras Superfamily G-proteins, Part A, Volume 33

1st Edition

Serial Volume Editor: Fuyuhiko Tamanoi
Hardcover ISBN: 9780124167490
eBook ISBN: 9780124169678
Imprint: Academic Press
Published Date: 8th August 2013
Page Count: 364
Sales tax will be calculated at check-out Price includes VAT/GST
Price includes VAT/GST

Institutional Subscription

Secure Checkout

Personal information is secured with SSL technology.

Free Shipping

Free global shipping
No minimum order.

Table of Contents

Chapter One. The Ras Superfamily G-Proteins

1 The Ras Superfamily G-Proteins

2 Overview of Structure, Activity, and Regulatory Proteins

3 Upstream and Downstream Signaling Pathways

4 Significance in Human Cancer

5 Strategies to Inhibit the Ras Superfamily G-Proteins



Chapter Two. NMR Study to Identify a Ligand-Binding Pocket in Ras

1 KRAS as a Drug Target

2 Nuclear Magnetic Resonance Fragment Screen

3 Protein Ligand Co-structures

4 Inhibition of SOS1-Mediated Nucleotide Exchange for RAS

5 Ligand-Binding Sites on Ras

6 Summary and Conclusions


Chapter Three. The Allosteric Switch and Conformational States in Ras GTPase Affected by Small Molecules

1 Introduction

2 Ras Architecture: The G Domain and Its Function

3 The Allosteric Switch in Ras-GTP and Its Role in Intrinsic Hydrolysis

4 The Allosteric Switch Linked to the Ras/Raf/MEK/ERK Pathway

5 Most Ras Structures in the Protein Data Bank are in the R State

6 Modulation of the Allosteric States in Ras-GTP by Small Molecules

7 Mapping the Binding Site Hot Spots in Ras: Targeting the Protein/Membrane Interface

8 Conclusions


Chapter Four. State 1(T) Inhibitors of Activated Ras

1 Introduction

2 Allosteric Regulation of the Ras–Effector Interaction

3 Identification of State 1(T) in Activated Ras by NMR Spectroscopy

4 Identification of 1(T) Inhibitors by NMR Spectroscopy

5 Metal-Cyclen Derivatives as 1(T) Inhibitors

6 Metal-BPA Derivatives as 1(T) Inhibitors

7 Outlook: Possible Applications to Other Small GTPases


Chapter Five. Sugar-Based Inhibitors of Ras Activation: Biological Activity and Identification of Ras–Inhibitor Binding Interface

1 Introduction

2 Initial Compounds and the Characterization of Ras–GDP Complex

3 New Ras Ligands from Natural Sugars

4 Ras Inhibitors with Improved Water Solubility

5 Conclusions



Chapter Six. Development of EHop-016: A Small Molecule Inhibitor of Rac

1 Introduction

2 Development of Rac Inhibitors to Impede Metastatic Cancer Progression

3 Future Directions



Chapter Seven. Aptamer-Derived Peptide Inhibitors of Rho Guanine Nucleotide Exchange Factors

1 Introduction

2 The Peptide Aptamer Technology: A Brief Overview

3 The Peptide Aptamer Technology Applied to the Identification of RhoGEF Inhibitors: Example of TRIPα Aptamer Targeting Trio

4 Peptide Aptamer Optimization as a Strategy to Identify Inhibitors of the Oncogenic RhoGEF Tgat

5 Conclusion—Perspectives



Chapter Eight. Targeting the Dbl and Dock-Family RhoGEFs: A Yeast-Based Assay to Identify Cell-Active Inhibitors of Rho-Controlled Pathways

1 Introduction

2 The YEA: Rationale and Principle

3 Applications

4 Concluding Remarks

5 Materials and Methods


Chapter Nine. Inhibitors of the ROCK Serine/Threonine Kinases: Key Effectors of the RhoA Small GTPase

1 Introduction

2 Fasudil and Y-27632

3 Proper Use of ROCK Inhibitors as Tools

4 Next-Generation ROCK Inhibitors

5 Future Directions for the Development of ROCK Inhibitors

6 Conclusions



Chapter Ten. A Two-Hybrid Approach to Identify Inhibitors of the RAS–RAF Interaction

1 Introduction

2 Outline of Discovery Process for MCP Compounds

3 Creation of a Y2H Strain with Improved Permeability

4 Selection of Novel RAS–RAF Protein Interaction Inhibitors in HTS in Hyperpermeable Yeast SKY54

5 Evaluation of Y2H-selected Compounds in SRE- and AP-1-Luciferase Secondary Screens in Mammalian Cell Lines

6 MCP Compounds Inhibit RAS-Induced Phosphorylation of the MAPK Pathway Kinases

7 MCP Compounds Block the Interaction between RAS and the RAF-RBD

8 Computational Docking of MCP110 to RAF

9 Probing the Anticancer Activity of MCP Compounds in Multiple Tumor Types

10 MCP Compounds Synergize with MAPK Pathway Inhibitors and Microtubule-Targeting Chemotherapeutics

11 Activity of MCP Compounds in Animal Models

12 Conclusion



Chapter Eleven. Inhibitors of K-Ras Plasma Membrane Localization

1 Introduction

2 Discovery Process for Inhibitors of Ras PM Localization

3 Staurosporines Inhibit Ras PM Localization by Blocking Phosphatidylserine Trafficking

4 Fendiline Inhibits K-Ras PM Targeting by an Off-Target Mechanism that is Unrelated to Calcium Channel Blockade

5 Metformin: A New Use as an Anticancer Therapeutic Targeting K-Ras

6 Conclusion and Future Directions



Chapter Twelve. Ras Chaperones: New Targets for Cancer and Immunotherapy

1 Introduction

2 Ras Chaperones are Targets for Ras Inhibition

3 FTS Analogs for Cancer Therapy

4 FTS in Combination with Other Agents for Cancer Therapy

5 Inhibition of Ras-Related Proteins by FTS

6 Ras in Orphan Diseases

7 FTS in the Immune System

8 FTS and Autoimmunity

9 FTS in Other Disease Models

10 Conclusions


Author Index

Subject Index


This special volume of The Enzymes is targeted toward researchers in biochemistry, molecular and cell biology, pharmacology, and cancer. This thematic volume discusses inhibitors of the Ras superfamily G-proteins.

Key Features

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


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


No. of pages:
© Academic Press 2013
8th August 2013
Academic Press
Hardcover ISBN:
eBook ISBN:

Ratings and Reviews

About the Serial Volume Editor

Fuyuhiko Tamanoi

Affiliations and Expertise

Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, USA