Phenotypic Drug Discovery.

Cover -- Preface -- Foreword: Phenotypic Drug Discovery: A Personal Perspective -- PDD Comes of Age -- Managing Risk -- Added Value -- Long-term Innovation -- Closing Remarks -- References -- 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 -- 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 -- 4.3 Functional Genomic Big Data Analytics and Artificial Intelligence -- 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 -- 6.4 Increasing the Throughput of Screening and Compound Triage -- 6.5 Target Deconvolution and Lead Optimization -- 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 Doesn't in Biomedical PPP? -- 7.4 Rationale for PDD in Industry and Academia -- 7.5 Rationale of PDD PPP and Three Academic Industrial Models -- 7.6 Conclusion/Outlook -- References -- Chapter 8 Identification of a Novel Class of Small Molecules for Spinal Muscular Atrophy Through High-throughput Phenotypic Screening -- 8.1 Introduction -- 8.2 Discovery of SMN2 Splicing Modulators Through Phenotypic Screening -- 8.3 Mechanism of Action Studies -- 8.4 Summary and Implications for Other Diseases -- Acknowledgements -- References -- Chapter 9 Antibody-based Phenotypic Screening - the Discovery of Oleclumab (MEDI9447) -- 9.1 Introduction -- 9.2 Phenotypic Screening Using Combinatorial Antibody Libraries -- 9.3 In vivo Characterisation of PHEN0203 and Validation of CD73 as an Antibody-tractable Target -- 9.4 Discovery of Oleclumab -- 9.5 Testing Oleclumab in the Clinic -- 9.6 Summary and Outlook -- References -- Chapter 10 Use of Phenotypic Screening in Mice in the Development of a Novel Non-D2-ReceptorTargeting Drug for the Treatment of Schizophren -- 10.1 Introduction -- 10.2 The Development of a Novel Drug Treatment of Schizophrenia -- 10.3 Other Programs in Development -- 10.4 Conclusions.

Acknowledgements -- References -- Chapter 11 Phenotypic Screening for Drug Discovery in Tuberculosis -- 11.1 Tuberculosis Disease -- 11.2 Phenotypic Screening for Tuberculosis -- 11.3 Contribution to Clinical Successes -- 11.4 Summary and Outlook -- Acknowledgements -- References -- Chapter 12 Why an In Vivo Screening Platform Covering Broad Therapeutic Spectrum is an Ideal Tool for Drug Repositioning: Illustrated by Discovery of a Novel Class of Insulin Sensitizers -- 12.1 The Problem That Needs to Be Solved -- 12.2 The Approach That Melior Has Taken to Address the Problem -- 12.3 The MLR-1023 Story -- 12.4 Lessons Learned from 15 Years of In Vivo Phenotypic Screening -- References -- Chapter 13 Phenotypic Screen Leads to Identification of Novel Posttranscriptional Regulation Machinery for HBV -- 13.1 Introduction -- 13.2 Identification of a Small-molecule Inhibitor of HBsAg -- 13.3 Unbiased MOA Studies -- 13.4 Proposal of a Novel Mechanism and Implications of New Targets for HBV Therapeutics -- References -- Subject Index.

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.

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Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, 2024. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries.