Phenotypic drug discovery Intro Half Title Title Copyright Preface Foreword Phenotypic Drug Discovery: A Personal Perspective Contents Chapter 1 Phenotypic Drug Discovery: History Evolution Future 1.1 Introduction 1.2 History 1.3 Translational Knowledge Gaps 1.4 Formalization of Empiricism into PDD 1.5 The Future of PDD References Chapter 2 Development and Validation of Disease Assays for Phenotypic Screening 2.1 Introduction 2.2 Assay Design: Connecting to Clinically Relevant Biology 2.3 Assay Performance: Planning for Analysis 2.4 Triage of Phenotypic Hits 2.5 Mechanism Classification of Phenotypic Hits 2.6 Early Compound De risking: Human Pharmacology based Screening Funnel 2.7 Challenges and Opportunities: Data Management and Analysis 2.8 Summary and Outlook Acknowledgements References Chapter 3 The Development and Use of Protein and Protein affinity Libraries for Phenotypic Screening 3.1 Introduction 3.2 Types of Protein Protein Affinity Tools for Phenotypic Screening 3.3 Application of Protein based Screening 6.4 Increasing the Throughput of Screening and Compound Triage 6.4.1 Compound centric 6.4.2 Target centric 6.5 Target Deconvolution and Lead Optimization 6.5.1 Identifying PhARTs 6.6 Discussion and Outlook Abbreviations Acknowledgements References Chapter 7 Public Private Partnerships to Advance Phenotypic Drug Discovery 7.1 Introduction 7.2 Collaborate to Advance Knowledge or to Compete 7.3 What Works and What Doesnt in Biomedical PPP 7.4 Rationale for PDD in Industry and Academia 7.4.1 The Role of PDD in Industry 3.4 A Case Study Using Secretome based Screening Identification of Potential Paracrine Factors that Stimulate Proliferaiton of Cardiac Cells in the Heart 3.5 Summary and Outlook Acknowledgements References Chapter 4 CRISPR Cas based Functional Genomic Approaches to Phenotypic Screening 4.1 Introduction 4.2 Phenotypic Screening with CRISPR Cas 4.2.1 CRISPR Guides RNA Libraries and Their Design 4.2.2 CRISPR based Screening Strategies for Target Identification 4.2.3 Hit Confirmation and Validation 4.3 Functional Genomic Big Data Analytics and Artificial Intelligence Phenotypic drug discovery has been highlighted in the past decade as an important strategy in the discovery of novel medical entities. This book aims to equip researchers with a thought provoking guide to the application and development of contemporary phenotypic drug discovery for clinical success 4.4 Summary and Outlook References Chapter 5 Contemporary Techniques for Target Deconvolution and Mode of Action Elucidation 5.1 Introduction 5.2 Affinity based Approaches 5.3 Functional Genomics Approaches 5.4 Cellular Profiling Approaches 5.5 Knowledge based and Computational Approaches 5.6 Discussion and Outlook References Chapter 6 Artificial Intelligence as an Enabler for Phenotypic Drug Discovery 6.1 Introduction 6.2 Data driven Assay Development 6.3 Accelerating Hit Discovery with Iterative Machine Learning