Target Identification and Validation in Drug Discovery

Methods and Protocols

Editors:

ISBN: 978-1-62703-310-7 (Print) 978-1-62703-311-4 (Online)

Table of contents (22 protocols)

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  1. Front Matter

    Pages i-xv

  2. Background

    1. Front Matter

      Pages 1-1

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      Pages 3-13

      The Path to Oncology Drug Target Validation: An Industry Perspective

  3. DNA as a Tool to Modulate Drug Targets

    1. Front Matter

      Pages 15-15

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      Pages 17-39

      Identification of Aptamers as Specific Binders and Modulators of Cell-Surface Receptor Activity

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      Pages 41-56

      The Design and Structure–Functional Properties of DNA-Based Immunomodulatory Sequences

  4. RNA Interference: From Design to Data Analysis

    1. Front Matter

      Pages 57-57

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      Pages 59-71

      siRNA Design Principles and Off-Target Effects

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      Pages 73-87

      Western Blot Evaluation of siRNA Delivery by pH-Responsive Peptides

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      Pages 89-95

      High-Throughput RNAi Screening for the Identification of Novel Targets

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      Pages 97-104

      Integration of RNAi and Small Molecule Screens to Identify Targets for Drug Development

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      Pages 105-122

      CellProfiler and KNIME: Open Source Tools for High Content Screening

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      Pages 123-137

      PARP Inhibition as a Prototype for Synthetic Lethal Screens

  5. Protein-Focused Technologies

    1. Front Matter

      Pages 139-139

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      Pages 141-164

      Structure-Based Target Druggability Assessment

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      Pages 165-178

      Validating Pharmacological Disruption of Protein–Protein Interactions by Acceptor Photobleaching FRET Imaging

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      Pages 179-185

      Systematic Analysis of Complex Signal Transduction Pathways Using Protein Fragment Complementation Assays

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      Pages 187-214

      Reverse Phase Protein Microarrays and Their Utility in Drug Development

  6. Innovative Cell Culture Techniques to Mimic Tissue Microenvironments

    1. Front Matter

      Pages 215-215

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      Pages 217-226

      A Cell Culture System That Mimics Chronic Lymphocytic Leukemia Cells Microenvironment for Drug Screening and Characterization

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      Pages 227-252

      Two-Dimensional vs. Three-Dimensional In Vitro Tumor Migration and Invasion Assays

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      Pages 253-266

      Tumor Spheroid-Based Migration Assays for Evaluation of Therapeutic Agents

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      Pages 267-277

      The Neurosphere Assay Applied to Neural Stem Cells and Cancer Stem Cells

  7. Genetically Engineered Animal Models to Study Gene Functions

    1. Front Matter

      Pages 279-279

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      Pages 281-305

      Genetically Engineered Animal Models for In Vivo Target Identification and Validation in Oncology

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      Pages 307-323

      Target Validation in Mice by Constitutive and Conditional RNAi

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      Pages 325-337

      In Vivo Target Validation by Inducible RNAi in Human Xenograft Mouse Models

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