Phenotypic Drug Discovery
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|Author||: Angelique Augustin,Beverley Isherwood|
|Publsiher||: Royal Society of Chemistry|
|Total Pages||: 245|
Download Phenotypic Drug Discovery Book in PDF, Epub and Kindle
Phenotypic drug discovery has been highlighted in the past decade as an important strategy in the discovery of new medical entities. How many marketed drugs are derived from phenotypic screens? From the most recent examples, what were the factors enabling target identification and validation? This book answers these questions by elaborating on fundamental capabilities required for phenotypic drug discovery and using case studies to illustrate approaches and key success factors. Written and edited by experienced practitioners from both industry and academia, this publication will equip researchers with a thought-provoking guide to the application and future development of contemporary phenotypic drug discovery for clinical success.
|Author||: Gul Erdemli,Birgit T Priest|
|Publsiher||: Frontiers Media SA|
|Total Pages||: 135|
|Genre||: Electronic Book|
Download Phenotypic screening in the 21st century Book in PDF, Epub and Kindle
In the genomic era of 1990s-2000s, pharmaceutical research moved to target-based drug discovery which enabled development of a number of small molecule drugs against a wide range of diseases. In many cases however, drugs that arose from genomics failed, questioning the validity of the targets and the suitability of target-based drug discovery as an optimal strategy for all disease states. For monogenic diseases, target-based approaches may be well-suited to the identification of novel therapies. Most diseases, however, are caused by a combination of several genetic and environmental factors and are likely to require simultaneous modulation of multiple molecular targets/pathways for successful treatment. For such diseases, reductionist approaches focusing on individual targets rather than biological networks are unlikely to succeed and new drug development strategies are required. In search of more successful approaches, the pharmaceutical industry is moving towards phenotypic screening beyond individual genes/targets. However, this requires rethinking of diseases and drug discovery approaches from a network and systems biology perspective. Since returning to the pre-genomics era of screening drug candidates in laborious animal models is not a feasible solution, the industry needs to evolve a new paradigm of phenotypic drug discovery within the context of systems biology. Such a paradigm must combine physiologically and disease relevant biological substrates with sufficient throughput, operational simplicity and statistical vigour. Biomarker strategies for translational medicine, as well as preclinical safety and selectivity assessments, would also need to be revised to adapt to the target agnostic style. This focused issue aims to discuss strategies, key concepts and technologies related to systems-based approaches in drug development. Design and implementation of innovative biological assays, featuring multiple target strategies, and rational drug design in the absence of target knowledge during the early drug discovery are illustrated with examples. Specific topics include: • The need for systems-based approaches in drug development • Phenotypic screening strategies • Compound libraries (natural product inspired compound collections) • Target deconvolution and identification • Target agnostic lead discovery and optimization • Multi-target approaches and decoding the phenotype (understanding biological interactions and multiscale systems modelling) • Translational aspects • Early evaluation of selectivity and safety in a target agnostic manner
|Author||: Taosheng Chen,Sergio Chai|
|Publsiher||: BoD – Books on Demand|
|Total Pages||: 190|
Download Special Topics in Drug Discovery Book in PDF, Epub and Kindle
Drug discovery involves multiple disciplines, technologies, and approaches. This book selects important topics related to drug discovery, including emerging tool (Chapter 1), cutting-edge approaches (Chapters 2, 3, and 4), examples of specific therapeutic area (Chapter 5), quality control in drug development (Chapter 6), and job and career opportunities in the pharmaceutical sector, a topic rarely covered by other books (Chapter 7). This book draws knowledge from experts actively involved in different areas of drug discovery from both industrial and academic settings. We hope that this book will facilitate your efforts in drug discovery.
|Author||: Paul A. Johnston,Oscar J. Trask|
|Publsiher||: Humana Press|
|Total Pages||: 397|
Download High Content Screening Book in PDF, Epub and Kindle
This second edition details some of the recent trends in HCS/HCA/HCI. New and updated chapters guide readers through methods that utilize reagents and kits that have been developed to measure cells and subpopulation classifications, control measures, overviews of the data handling issues associated with HCS/HCA/HCI, and methods to implement more complex phenotypic models. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, High Content Screening and Analysis-The Ideal Format for Phenotypic Screening: A Powerful Approach to Systems Cell Biology and Drug Discovery, Second Edition aims to ensure successful results in the further study of this vital field.
|Author||: János Fischer,David P. Rotella|
|Publsiher||: John Wiley & Sons|
|Total Pages||: 256|
Download Successful Drug Discovery Book in PDF, Epub and Kindle
The first volume of the book series "Successful Drug Discovery" is focusing on new drug discoveries during the last decade, from established drugs to recently introduced drugs of all kinds: small-molecule-, peptide-, and protein-based drugs. The role of serendipity is analyzed in some very successful drugs where the research targets of the lead molecule and the drug are different. Phenotypic and target-based drug discovery approaches are discussed from the viewpoint of pioneer drugs and analogues. This volume gives an excellent overview of insulin analogues including a discussion of the properties of rapid-acting and long-acting formulations of this important hormone. The major part of the book is devoted to case histories of new drug discoveries described by their key inventors. Eight case histories range across many therapeutic fields. The goal of this book series is to help the participants of the drug research community with a reference book series and to support teaching in medicinal chemistry with case histories and review articles of new drugs.
|Author||: J. Richard Morphy,C John Harris|
|Publsiher||: Royal Society of Chemistry|
|Total Pages||: 394|
Download Designing Multi Target Drugs Book in PDF, Epub and Kindle
Multi-target drug discovery (MTDD) is an emerging area of increasing interest to the drug discovery community. Drugs that modulate several targets have the potential for an improved balance of efficacy and safety compared to single targets agents. Although there are a number of marketed drugs that are thought to derive their therapeutic benefit by virtue of interacting with multiple targets, the majority of these were discovered accidentally. Written by world renowned experts, this is the first book to gather together knowledge and experiences of the rational discovery of multi-target drugs. It describes the current state of the art, the achievements and the challenges of the field and importantly the lessons learned by researchers to date and their application to future MTDD.
|Author||: Farid A. Badria|
|Publsiher||: BoD – Books on Demand|
|Total Pages||: 234|
Download Drug Repurposing Book in PDF, Epub and Kindle
Drug repurposing or drug repositioning is a new approach to presenting new indications for common commercial and clinically approved existing drugs. For example, chloroquine, an old antimalarial drug, showed promising results for treating COVID-19, interfering with MDR in several types of cancer, and chemosensitizing human leukemic cells.This book focuses on the hypothesis, risk/benefits, and economic impacts of drug repurposing on drug discovery in dermatology, infectious diseases, neurological disorders, cancer, and orphan diseases. It brings together up-to-date research to provide readers with an informative, illustrative, and easy-to-read book useful for students, clinicians, and the pharmaceutical industry.
|Author||: Institute of Medicine,Board on Health Sciences Policy,Forum on Neuroscience and Nervous System Disorders|
|Publsiher||: National Academies Press|
|Total Pages||: 118|
Download Improving and Accelerating Therapeutic Development for Nervous System Disorders Book in PDF, Epub and Kindle
Improving and Accelerating Therapeutic Development for Nervous System Disorders is the summary of a workshop convened by the IOM Forum on Neuroscience and Nervous System Disorders to examine opportunities to accelerate early phases of drug development for nervous system drug discovery. Workshop participants discussed challenges in neuroscience research for enabling faster entry of potential treatments into first-in-human trials, explored how new and emerging tools and technologies may improve the efficiency of research, and considered mechanisms to facilitate a more effective and efficient development pipeline. There are several challenges to the current drug development pipeline for nervous system disorders. The fundamental etiology and pathophysiology of many nervous system disorders are unknown and the brain is inaccessible to study, making it difficult to develop accurate models. Patient heterogeneity is high, disease pathology can occur years to decades before becoming clinically apparent, and diagnostic and treatment biomarkers are lacking. In addition, the lack of validated targets, limitations related to the predictive validity of animal models - the extent to which the model predicts clinical efficacy - and regulatory barriers can also impede translation and drug development for nervous system disorders. Improving and Accelerating Therapeutic Development for Nervous System Disorders identifies avenues for moving directly from cellular models to human trials, minimizing the need for animal models to test efficacy, and discusses the potential benefits and risks of such an approach. This report is a timely discussion of opportunities to improve early drug development with a focus toward preclinical trials.
|Author||: Juan Bueno|
|Publsiher||: Academic Press|
|Total Pages||: 192|
Download Molecular Evolutionary Models in Drug Discovery Book in PDF, Epub and Kindle
Molecular Evolutionary Models in Drug Discovery explores the application of evolutionary molecular models in drug discovery in which secondary metabolites play a fundamental role. Secondary metabolites are not produced in isolation, they are the result of the interaction of genes, metabolism and the environment. The book examines the role of secondary metabolites as leads in drug discovery and on the development of a rational bioprospecting model for new medicines based on the evolution of secondary metabolism. These evolutionary models are part of biological systems and are the most reliable expression of the functioning of living beings. Examines the integration and application of evolutionary models in the pharmaceutical industry to create new drug development platforms Investigates the biotechnological prospecting of secondary metabolites and their potential use in the discovery of new drugs Evaluates the ecosystem of living beings and how its molecular adaptation might improve the success of therapies
|Author||: Donald C. Lo,Robert E. Hughes|
|Publsiher||: CRC Press|
|Total Pages||: 338|
Download Neurobiology of Huntington s Disease Book in PDF, Epub and Kindle
In 1993, the genetic mutation responsible for Huntington’s disease (HD) was identified. Considered a milestone in human genomics, this discovery has led to nearly two decades of remarkable progress that has greatly increased our knowledge of HD, and documented an unexpectedly large and diverse range of biochemical and genetic perturbations that seem to result directly from the expression of the mutant huntingtin gene. Neurobiology of Huntington’s Disease: Applications to Drug Discovery presents a thorough review of the issues surrounding drug discovery and development for the treatment of this paradigmatic neurodegenerative disease. Drawing on the expertise of key researchers in the field, the book discusses the basic neurobiology of Huntington’s disease and how its monogenic nature confers enormous practical advantages for translational research, including the creation of robust experimental tools, models, and assays to facilitate discovery and validation of molecular targets and drug candidates for HD. Written to support future basic research as well as drug development efforts, this volume: Covers the latest research approaches in genetics, genomics, and proteomics, including high-throughput and high-content screening Highlights advances in the discovery and development of new drug therapies for neurodegenerative disorders Examines the practical realities of preclinical testing, clinical testing strategies, and, ultimately, clinical usage While the development of effective drug treatments for Huntington's disease continues to be tremendously challenging, a highly interactive and cooperative community of researchers and clinical investigators now brings us to the threshold of potential breakthroughs in the quest for therapeutic agents. The impressive array of drug discovery resources outlined in the text holds much promise for treating this devastating disease, providing hope to long-suffering Huntington’s disease patients and their families.
|Author||: Joshua A. Bittker,Nathan T. Ross|
|Publsiher||: Royal Society of Chemistry|
|Total Pages||: 396|
Download High Throughput Screening Methods Book in PDF, Epub and Kindle
High throughput screening remains a key part of early stage drug and tool compound discovery, and methods and technologies have seen many fundamental improvements and innovations over the past 20 years. This comprehensive book provides a historical survey of the field up to the current state-of-the-art. In addition to the specific methods, this book also considers cultural and organizational questions that represent opportunities for future success. Following thought-provoking foreword and introduction from Professor Stuart Schreiber and the editors, chapters from leading experts across academia and industry cover initial considerations for screening, methods appropriate for different goals in small molecule discovery, newer technologies that provide alternative approaches to traditional miniaturization procedures, and practical aspects such as cost and resourcing. Within the context of their historical development, authors explain common pitfalls and their solutions. This book will serve as both a practical reference and a thoughtful guide to the philosophy underlying technological change in such a fast-moving area for postgraduates and researchers in academia and industry, particularly in the areas of chemical biology, pharmacology, structural biology and assay development.
|Author||: Andrea Trabocchi,Elena Lenci|
|Total Pages||: 356|
Download Small Molecule Drug Discovery Book in PDF, Epub and Kindle
Small Molecule Drug Discovery: Methods, Molecules and Applications presents the methods used to identify bioactive small molecules, synthetic strategies and techniques to produce novel chemical entities and small molecule libraries, chemoinformatics to characterize and enumerate chemical libraries, and screening methods, including biophysical techniques, virtual screening and phenotypic screening. The second part of the book gives an overview of privileged cyclic small molecules and major classes of natural product-derived small molecules, including carbohydrate-derived compounds, peptides and peptidomimetics, and alkaloid-inspired compounds. The last section comprises an exciting collection of selected case studies on drug discovery enabled by small molecules in the fields of cancer research, CNS diseases and infectious diseases. The discovery of novel molecular entities capable of specific interactions represents a significant challenge in early drug discovery. Small molecules are low molecular weight organic compounds that include natural products and metabolites, as well as drugs and other xenobiotics. When the biological target is well defined and understood, the rational design of small molecule ligands is possible. Alternatively, small molecule libraries are being used for unbiased assays for complex diseases where a target is unknown or multiple factors contribute to a disease pathology. Outlines modern concepts and synthetic strategies underlying the building of small molecules and their chemical libraries useful for drug discovery Provides modern biophysical methods to screening small molecule libraries, including high-throughput screening, small molecule microarrays, phenotypic screening and chemical genetics Presents the most advanced chemoinformatics tools to characterize the structural features of small molecule libraries in terms of chemical diversity and complexity, also including the application of virtual screening approaches Gives an overview of structural features and classification of natural product-derived small molecules, including carbohydrate derivatives, peptides and peptidomimetics, and alkaloid-inspired small molecules
|Author||: Alleyn T. Plowright|
|Publsiher||: John Wiley & Sons|
|Total Pages||: 400|
Download Target Discovery and Validation Book in PDF, Epub and Kindle
The modern drug developers? guide for making informed choices among the diverse target identification methods Target Discovery and Validation: Methods and Strategies for Drug Discovery offers a hands-on review of the modern technologies for drug target identification and validation. With contributions from noted industry and academic experts, the book addresses the most recent chemical, biological, and computational methods. Additionally, the book highlights techologies that are applicable to ?difficult? targets and drugs directed at multiple targets, including chemoproteomics, activity-based protein profiling, pathway mapping, genome-wide association studies, and array-based profiling. Throughout, the authors highlight a range of diverse approaches, and target validation studies reveal how these methods can support academic and drug discovery scientists in their target discovery and validation research. This resource: -Offers a guide to identifying and validating targets, a key enabling technology without which no new drug development is possible -Presents the information needed for choosing the appropriate assay method from the ever-growing range of available options -Provides practical examples from recent drug development projects, e. g. in kinase inhibitor profiling Written for medicinal chemists, pharmaceutical professionals, biochemists, biotechnology professionals, and pharmaceutical chemists, Target Discovery and Validation explores the current methods for the identification and validation of drug targets in one comrpehensive volume. It also includes numerous practical examples.
|Author||: Bhushan Patwardhan,Rathnam Chaguturu|
|Publsiher||: Academic Press|
|Total Pages||: 480|
Download Innovative Approaches in Drug Discovery Book in PDF, Epub and Kindle
Despite considerable technological advances, the pharmaceutical industry is experiencing a severe innovation deficit, especially in the discovery of new drugs. Innovative Approaches in Drug Discovery: Ethnopharmacology, Systems Biology and Holistic Targeting provides a critical review and analysis of health, disease and medicine, and explores possible reasons behind the present crisis in drug discovery. The authors illustrate the benefits of systems biology and pharmacogenomics approaches, and advocate the expansion from disease-centric discovery to person-centric therapeutics involving holistic, multi-target, whole systems approaches. This book lays a path for reigniting pharmaceutical innovation through a disciplined reemergence of pharmacognosy, embracing open innovation models and collaborative, trusted public-private partnerships. With unprecedented advances made in the development of biomedically-relevant tools and technologies, the need is great and the time is now for a renewed commitment towards expanding the repertoire of medicines. By incorporating real-life examples and state-of-the-art reviews, this book provides valuable insights into the discovery and development strategies for professionals, academicians, and students in the pharmaceutical sciences. Analyzes the reasons behind historical drug failures to provide valuable insights on lessons learned Uses current scientific research to promote learning from traditional knowledge systems and through the integration of traditional and western medicines Discusses advances in technologies and systems biology to support the transition from formulation discovery to therapeutic discovery