Linked e-resources
Details
Table of Contents
Intro; Preface; Contents; Contributors; Current Strategies for the Discovery of Small-Molecule Inhibitors of Protein-Protein Interactions; 1 Overview of Protein-Protein Interactions and Small-Molecule Inhibitors Under Clinical Development; 1.1 Introduction; 1.2 Challenges in the Discovery of Small-Molecule PPI Inhibitors; 1.3 Structures and Classifications of PPIs; 1.4 "Hot Spots" as Structural Basis for the Design of Small-Molecule PPI Inhibitors; 1.5 Overview of Strategies for the Design of Small-Molecule PPI Inhibitors; 1.6 Small-Molecule PPI Inhibitors Under Clinical Development
1.6.1 Fragment-Based Discovery of Bcl-2 Inhibitor Venetoclax1.6.2 Discovery of LFA-1/ICAM-1 Inhibitor Lifitegrast for the Treatment of Dry Eye Syndrome; 1.7 Conclusions; References; 2 High-Throughput Screening in the Discovery of Small-Molecule Inhibitors of Protein-Protein Interactions; 2.1 Introduction; 2.2 Compound Libraries for HTS of PPI Inhibitors; 2.2.1 MCR-Inspired Compound Library; 2.2.2 DOS-Inspired Compound Library; 2.2.3 Cascade Reaction-Inspired Compound Library; 2.2.4 BIOS-Inspired Compound Library; 2.3 Assays for HTS of PPI Inhibitors; 2.3.1 FP Assay; 2.3.2 FRET Assay
4 Computational Methods Applicable to the Discovery of Small-Molecule Inhibitors of Protein-Protein Interactions4.1 Background; 4.2 Computational Methods Used for Characterizing PPIs; 4.2.1 Selecting a PPI Target; 4.2.2 Homology Modeling of Protein Structures; 4.2.3 Protein-Protein Molecular Docking; 4.2.4 Identifying Hot Spots on PPI Interfaces; 4.3 Computational Methods Used for Designing PPI Inhibitors; 4.3.1 Virtual Screening; 4.3.2 Fragment-Based Design; 4.4 Example Applications of Computational Methods for PPI Inhibitor Discovery
4.4.1 Case 1: A Pharmacophore-Based Strategy Used in the Design of p53-MDM2 Inhibitors4.4.2 Case 2: Discovery of uPA-uPAR Inhibitors Through a Docking-Based Virtual Screening; 4.4.3 Case 3: Discovery of IL-6/GP130 Interaction Inhibitors Through Multi-fragment Docking; 4.4.4 Case 4: Development of a Bcl-2 Inhibitor via a Fragment-Based De Novo Design; 4.5 Conclusion; Acknowledgements; References; 5 Experimental Methods Used for Identifying Small-Molecule Inhibitors of Protein-Protein Interaction; 5.1 Introduction; 5.2 Biophysical Methods; 5.2.1 Fluorescence Polarization (FP)
1.6.1 Fragment-Based Discovery of Bcl-2 Inhibitor Venetoclax1.6.2 Discovery of LFA-1/ICAM-1 Inhibitor Lifitegrast for the Treatment of Dry Eye Syndrome; 1.7 Conclusions; References; 2 High-Throughput Screening in the Discovery of Small-Molecule Inhibitors of Protein-Protein Interactions; 2.1 Introduction; 2.2 Compound Libraries for HTS of PPI Inhibitors; 2.2.1 MCR-Inspired Compound Library; 2.2.2 DOS-Inspired Compound Library; 2.2.3 Cascade Reaction-Inspired Compound Library; 2.2.4 BIOS-Inspired Compound Library; 2.3 Assays for HTS of PPI Inhibitors; 2.3.1 FP Assay; 2.3.2 FRET Assay
4 Computational Methods Applicable to the Discovery of Small-Molecule Inhibitors of Protein-Protein Interactions4.1 Background; 4.2 Computational Methods Used for Characterizing PPIs; 4.2.1 Selecting a PPI Target; 4.2.2 Homology Modeling of Protein Structures; 4.2.3 Protein-Protein Molecular Docking; 4.2.4 Identifying Hot Spots on PPI Interfaces; 4.3 Computational Methods Used for Designing PPI Inhibitors; 4.3.1 Virtual Screening; 4.3.2 Fragment-Based Design; 4.4 Example Applications of Computational Methods for PPI Inhibitor Discovery
4.4.1 Case 1: A Pharmacophore-Based Strategy Used in the Design of p53-MDM2 Inhibitors4.4.2 Case 2: Discovery of uPA-uPAR Inhibitors Through a Docking-Based Virtual Screening; 4.4.3 Case 3: Discovery of IL-6/GP130 Interaction Inhibitors Through Multi-fragment Docking; 4.4.4 Case 4: Development of a Bcl-2 Inhibitor via a Fragment-Based De Novo Design; 4.5 Conclusion; Acknowledgements; References; 5 Experimental Methods Used for Identifying Small-Molecule Inhibitors of Protein-Protein Interaction; 5.1 Introduction; 5.2 Biophysical Methods; 5.2.1 Fluorescence Polarization (FP)