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Target Validation in Drug Discovery

Target Validation in Drug Discovery
  • Author : Brian W. Metcalf,Susan Dillon
  • Publisher :Unknown
  • Release Date :2011-04-28
  • Total pages :296
  • ISBN : 0080465978
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Summary : This work presents a comprehensive contemporary framework for approaching target validation in drug discovery. It begins with a detailed description of new enabling technologies, including aptamers, RNA interference, functional genomics, and proteomics. The next section looks at biologic drug development with in-depth discussion of lessons learned from such well-known cases as Erbitux, Herceptin, and Avastin. Additional targets known as "second generation" drugs, which can be identified when disease pathways are validated by biologics, present new possible small molecule therapeutics and serve as the focus of the final section of the book.

Target Discovery and Validation

Target Discovery and Validation
  • Author : Alleyn T. Plowright
  • Publisher :Unknown
  • Release Date :2019-12-31
  • Total pages :400
  • ISBN : 9783527345298
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Summary : 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.

Target Identification and Validation in Drug Discovery

Target Identification and Validation in Drug Discovery
  • Author : Jurgen Moll,Riccardo Colombo
  • Publisher :Unknown
  • Release Date :2016-05-01
  • Total pages :388
  • ISBN : 1493962787
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Summary : This Methods in Molecular Biology book details current procedures for identifying and validating new drug targets. Includes methods and approaches covering biochemical, cell based, in vivo models and translational methods, as well as relevant case reports."

Improving and Accelerating Therapeutic Development for Nervous System Disorders

Improving and Accelerating Therapeutic Development for Nervous System Disorders
  • Author : Institute of Medicine,Board on Health Sciences Policy,Forum on Neuroscience and Nervous System Disorders
  • Publisher :Unknown
  • Release Date :2014-02-06
  • Total pages :118
  • ISBN : 9780309292498
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Summary : 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.

In Silico Technologies in Drug Target Identification and Validation

In Silico Technologies in Drug Target Identification and Validation
  • Author : Darryl Leon,Scott Markel
  • Publisher :Unknown
  • Release Date :2006-06-13
  • Total pages :504
  • ISBN : 9781420015737
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Summary : The pharmaceutical industry relies on numerous well-designed experiments involving high-throughput techniques and in silico approaches to analyze potential drug targets. These in silico methods are often predictive, yielding faster and less expensive analyses than traditional in vivo or in vitro procedures. In Silico Technologies in Drug Target Identification and Validation addresses the challenge of testing a growing number of new potential targets and reviews currently available in silico approaches for identifying and validating these targets. The book emphasizes computational tools, public and commercial databases, mathematical methods, and software for interpreting complex experimental data. The book describes how these tools are used to visualize a target structure, identify binding sites, and predict behavior. World-renowned researchers cover many topics not typically found in most informatics books, including functional annotation, siRNA design, pathways, text mining, ontologies, systems biology, database management, data pipelining, and pharmacogenomics. Covering issues that range from prescreening target selection to genetic modeling and valuable data integration, In Silico Technologies in Drug Target Identification and Validation is a self-contained and practical guide to the various computational tools that can accelerate the identification and validation stages of drug target discovery and determine the biological functionality of potential targets more effectively. Daniel E. Levy, editor of the Drug Discovery Series, is the founder of DEL BioPharma, a consulting service for drug discovery programs. He also maintains a blog that explores organic chemistry.

Target Discovery and Validation

Target Discovery and Validation
  • Author : Mouldy Sioud
  • Publisher :Unknown
  • Release Date :2007
  • Total pages :384
  • ISBN : 9781597451659
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Summary : Annotation These volumes review the most current methods for drug target discovery and validation. They explore how recent improvement in understanding the molecular mechanisms of human pathology is impacting drug target discovery in the laboratory and in real therapeutics, specifically for cancers and autoimmune disorders. This book provides a thorough review of the most cutting-edge methods available for each step in drug target identification, validation, and clinical application.

Platform Technologies in Drug Discovery and Validation

Platform Technologies in Drug Discovery and Validation
  • Author : Anonim
  • Publisher :Unknown
  • Release Date :2017-11-21
  • Total pages :690
  • ISBN : 9780128130704
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Summary : Platform Technologies in Drug Discovery and Validation, Volume 50, the latest release in the Annual Reports in Medicinal Chemistry series, provides timely and critical reviews of important topics in medicinal chemistry, with an emphasis on emerging topics in the biological sciences. Topics covered in this new volume include DELT, Oligos: ASO, siRNA, CRISPR, Micro-fluidic chemistry, High throughput screening, Kinase-centric computational drug development, Virtual Screening, Phenotypic screening, PROTACS, Chemical Biology, Fragment-based lead generation, Antibody-Drug Conjugates, Antibody-recruiting small molecules, Deuteration, and Peptides. Unique for its treatment of platform technologies for medicinal chemistry and target validation Provides a single, rich volume that summaries a broad spectrum of expertise relevant to the field Presents state-of-the-art summaries of platform technologies

Neurobiology of Huntington’s Disease

Neurobiology of Huntington’s Disease
  • Author : Donald C. Lo,Robert E. Hughes
  • Publisher :Unknown
  • Release Date :2010-07-02
  • Total pages :338
  • ISBN : 9781420008258
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Summary : 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.

Phenotypic Drug Discovery

Phenotypic Drug Discovery
  • Author : Beverley Isherwood,Angelique Augustin
  • Publisher :Unknown
  • Release Date :2020-12-10
  • Total pages :272
  • ISBN : 9781839160790
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Summary : 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.

Target Identification and Validation in Drug Discovery

Target Identification and Validation in Drug Discovery
  • Author : Jürgen Moll,Sebastian Carotta
  • Publisher :Unknown
  • Release Date :2019-04-12
  • Total pages :318
  • ISBN : 1493991442
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Summary : This second edition book explores breakthrough technologies in the field of drug target identification and validation. The volume emphasizes particularly revolutionary technologies, such as CRISPR-related screening, “big data,” and in silico approaches, as well as in vivo applications of CRISPR and best uses of animal models in drug development. Written for the highly successful Methods in Molecular Biology series, 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. Fully updated and authoritative, Target Identification and Validation in Drug Discovery: Methods and Protocols, Second Edition is an ideal guide for molecular and cellular biologists, pharmacologists, pathologists, bioinformaticians, clinical researchers, or investigators, as well as experts in other fields that need a quick overview of these state-of-the-art technologies.

Real World Drug Discovery

Real World Drug Discovery
  • Author : Robert M. Rydzewski
  • Publisher :Unknown
  • Release Date :2010-07-07
  • Total pages :600
  • ISBN : 0080914888
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Summary : Drug discovery increasingly requires a common understanding by researchers of the many and diverse factors that go into the making of new medicines. The scientist entering the field will immediately face important issues for which his education may not have prepared him: project teams, patent law, consultants, target product profiles, industry trends, Gantt charts, target validation, pharmacokinetics, proteomics, phenotype assays, biomarkers, and many other unfamiliar topics for which a basic understanding must somehow be obtained. Even the more experienced scientist can find it frustratingly difficult to get an overview of the many factors involved in modern drug discovery and often only after years of exploring does a whole and integrated picture emerge in the mind of the researcher. Real World Drug Discovery: A Chemist’s Guide to Biotech and Pharmaceutical Research presents this kind of map of the landscape of drug discovery. In a single, readable volume it outlines processes and explains essential concepts and terms for the recent science graduate wondering what to expect in pharma or biotech, the medicinal chemist seeking a broader and more timely understanding of the industry, or the contractor or collaborator whose understanding of the commercial drug discovery process could increase the value of his contribution to it. Interviews with well-known experts in many of the fields involved, giving insightful comments from authorities on many of the sub-disciplines important to cutting edge drug discovery. Helpful suggestions gleaned from years of experience in biotech and pharma, which represents a repository drug discovery "lore" not previously available in any book. "Periodic Table of Drugs" listing current top-selling drugs arranged by target and laid out so that structural similarities and differences are plain and clear. Extensive use of diagrams to illustrate concepts like biotech startup models, preteomic profiling for target identification, Gantt charts for project planning, etc.

The Design and Development of Novel Drugs and Vaccines

The Design and Development of Novel Drugs and Vaccines
  • Author : Tarun Kumar Bhatt,Surendra Nimesh
  • Publisher :Unknown
  • Release Date :2021-01-21
  • Total pages :308
  • ISBN : 9780128214756
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Summary : The Design and Development of Novel Drugs and Vaccines: Principles and Protocols presents both in silico methods and experimental protocols for vaccine and drug design and development, critically reviewing the most current research and emphasizing approaches and technologies that accelerate and lower the cost of product development. Sections review the technologies and approaches used to identify, characterize and establish a protein as a new drug and vaccine target, cover several molecular methods for in vitro studies of the desired target, and present various physiological parameters for in vivo studies. The book includes preclinical trials and research, along with information on FDA approval. Covers both in silico methods and experimental protocols for vaccine and drug development in a single, accessible volume Offers a holistic accounting of how developments in bioinformatics and large experimental datasets can be used in the development of vaccines and drugs Shows researchers the entire gamut of current therapies, ranging from computational inputs to animal studies Reviews the most current, cutting-edge research available on vaccine and drug design and development

Deriving Drug Discovery Value from Large-Scale Genetic Bioresources

Deriving Drug Discovery Value from Large-Scale Genetic Bioresources
  • Author : National Academies of Sciences, Engineering, and Medicine,Health and Medicine Division,Board on Health Sciences Policy,Forum on Drug Discovery, Development, and Translation,Roundtable on Genomics and Precision Health
  • Publisher :Unknown
  • Release Date :2016-12-02
  • Total pages :114
  • ISBN : 9780309447782
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Summary : The process of discovering and developing a new drug or therapy is extremely costly and time consuming, and recently, it has been estimated that the creation of a new medicine costs on average more than $2 billion and takes 10 years to reach patients. The challenges associated with bringing new medicines to market have led many pharmaceutical companies to seek out innovative methods for streamlining their drug discovery research. One way to increase the odds of success for compounds in the drug development pipeline is to adopt genetically guided strategies for drug discovery, and recognizing the potential benefits of collecting genetic and phenotypic information across specific populations, pharmaceutical companies have started collaborating with healthcare systems and private companies that have curated genetic bioresources, or large databases of genomic information. Large-scale cohort studies offer an effective way to collect and store information that can be used to assess geneâ€"environment interactions, identify new potential drug targets, understand the role of certain genetic variants in the drug response, and further elucidate the underlying mechanisms of disease onset and progression. To examine how genetic bioresources could be used to improve drug discovery and target validation, the National Academies of Sciences, Engineering, and Medicine hosted a workshop in March 2016. Participants at the workshop explored the current landscape of genomics-enabled drug discovery activities in industry, academia, and government; examined enabling partnerships and business models; and considered gaps and best practices for collecting population data for the purpose of improving the drug discovery process. This publication summarizes the presentations and discussions from the workshop.

The Discovery and Utility of Chemical Probes in Target Discovery

The Discovery and Utility of Chemical Probes in Target Discovery
  • Author : Paul Brennan,Saleta Vazquez-Rodriguez
  • Publisher :Unknown
  • Release Date :2020-11-25
  • Total pages :320
  • ISBN : 9781788015899
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Summary : Numerous genetic methods can be utilised to link a phenotype to a single molecular target but annotated small molecule chemical probes and even entire chemogenomic libraries are increasingly being used as a complementary approach. This book will comprehensively cover the state of the art in chemical probes and best practice for use in target discovery, illustrated throughout with examples. Ideal for students and established biochemists, the book will also cover new technologies for probe discovery, new probe modalities, the new field of probes for RNA targets and the mature field of kinase chemical probes.

Biochips as Pathways to Drug Discovery

Biochips as Pathways to Drug Discovery
  • Author : Gary Hardiman
  • Publisher :Unknown
  • Release Date :2006-10-19
  • Total pages :386
  • ISBN : 9781420015607
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Summary : In the fiercely competitive pharmaceutical marketplace, your organization cannot afford to spend excess dollars developing drugs that will fail to get FDA approval or have profoundly poor characteristics. Biochips as Pathways to Drug Discovery takes a comprehensive look at how the industry faces these challenges, using new technologies such as biochips to reduce the cost of drug discovery and improve drug safety. The book explores the tools and skills required at each step of the discovery process when using biochips to determine biological outcomes. The authors provide an in-depth review of the clinical and pharmacogenomic relevance of biochips, ChIP-chip assays, and high-throughput approaches. They discuss how biochips are used to develop biomarkers in the drug discovery process, primarily for gene expression profiling and Single Nucleotide Polymorphism (SNP) analysis. The book includes coverage of experimental theory, quality control, clinical laboratory sampling considerations, database concepts, industrial laboratory design, and the analysis of the resultant large data sets. It discusses the application of biochips to the study of malaria, toxicogenomics, and SNPs, as well as intellectual property and market overviews. The book concludes with a comprehensive overview of how these chips are employed from early target discovery through preclinical toxicology and on through to pharmacogenomic and proof of concept studies in humans. Written in an easily accessible style, the breadth of coverage introduces the subject to those new to the field, while the depth of coverage forms a foundation for future work. The book gives you the knowledge required to leverage the technology into bona fide discoveries. Daniel E. Levy, editor of the Drug Discovery Series, is the founder of DEL BioPharma, a consulting service for drug discovery programs. He also maintains a blog that explores organic chemistry.

Artificial Neural Network for Drug Design, Delivery and Disposition

Artificial Neural Network for Drug Design, Delivery and Disposition
  • Author : Munish Puri,Yashwant Pathak,Vijay Kumar Sutariya,Srinivas Tipparaju,Wilfrido Moreno
  • Publisher :Unknown
  • Release Date :2015-10-15
  • Total pages :440
  • ISBN : 9780128017449
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Summary : Artificial Neural Network for Drug Design, Delivery and Disposition provides an in-depth look at the use of artificial neural networks (ANN) in pharmaceutical research. With its ability to learn and self-correct in a highly complex environment, this predictive tool has tremendous potential to help researchers more effectively design, develop, and deliver successful drugs. This book illustrates how to use ANN methodologies and models with the intent to treat diseases like breast cancer, cardiac disease, and more. It contains the latest cutting-edge research, an analysis of the benefits of ANN, and relevant industry examples. As such, this book is an essential resource for academic and industry researchers across the pharmaceutical and biomedical sciences. Written by leading academic and industry scientists who have contributed significantly to the field and are at the forefront of artificial neural network (ANN) research Focuses on ANN in drug design, discovery and delivery, as well as adopted methodologies and their applications to the treatment of various diseases and disorders Chapters cover important topics across the pharmaceutical process, such as ANN in structure-based drug design and the application of ANN in modern drug discovery Presents the future potential of ANN-based strategies in biomedical image analysis and much more

Model Organisms in Drug Discovery

Model Organisms in Drug Discovery
  • Author : Pamela M. Carroll,Kevin Fitzgerald
  • Publisher :Unknown
  • Release Date :2004-04-21
  • Total pages :302
  • ISBN : 9780470871300
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Summary : Fruit flies are "little people with wings" goes the saying in the scientific community, ever since the completion of the Human Genome Project and its revelations about the similarity amongst the genomes of different organisms. It is humbling that most signalling pathways which "define" humans are conserved in Drosophila, the common fruit fly. Feed a fruit fly caffeine and it has trouble falling asleep; feed it antihistamines and it cannot stay awake. A C. elegans worm placed on the antidepressant flouxetine has increased serotonin levels in its tiny brain. Yeast treated with chemotherapeutics stop their cell division. Removal of a single gene from a mouse or zebrafish can cause the animals to develop Alzheimer’s disease or heart disease. These organisms are utilized as surrogates to investigate the function and design of complex human biological systems. Advances in bioinformatics, proteomics, automation technologies and their application to model organism systems now occur on an industrial scale. The integration of model systems into the drug discovery process, the speed of the tools, and the in vivo validation data that these models can provide, will clearly help definition of disease biology and high-quality target validation. Enhanced target selection will lead to the more efficacious and less toxic therapeutic compounds of the future. Leading experts in the field provide detailed accounts of model organism research that have impacted on specific therapeutic areas and they examine state-of-the-art applications of model systems, describing real life applications and their possible impact in the future. This book will be of interest to geneticists, bioinformaticians, pharmacologists, molecular biologists and people working in the pharmaceutical industry, particularly genomics.

Molecular Cancer Therapeutics

Molecular Cancer Therapeutics
  • Author : George C. Prendergast
  • Publisher :Unknown
  • Release Date :2004-04-02
  • Total pages :351
  • ISBN : 0471432024
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Summary : Molecular Cancer Therapeutics covers state-of-the-art strategies to identify and develop cancer drug target molecules and lead inhibitors for clinical testing. It provides a thorough treatment of drug target discovery, validation, and development. The introductory chapters provide an overview of pathways to discovery and development of molecular cancer therapeutics. Subsequent chapters progress from initial stages of drug target discovery to drug discovery, development, and testing in preclinical and clinical models. Topics include drug lead screening, drug-to-lead development, proof-of-concept studies, medicinal chemistry issues, intellectual property concerns, and clinical development. This invaluable reference promotes understanding of steps involved in developing drug leads for industrial partnering and development. It provides an overview of the strategies for discovery and validation of drug target molecules, and discusses cell- and molecule-based drug screening strategies, as well as mouse models for cancer. Coverage also includes how to refine drug leads for suitability in clinical testing, the special issues of clinical testing of molecular-targeted drugs, and intellectual property concerns.

Modern Methods of Drug Discovery

Modern Methods of Drug Discovery
  • Author : Alexander Hillisch,Rolf Hilgenfeld
  • Publisher :Unknown
  • Release Date :2012-11-28
  • Total pages :292
  • ISBN : 9783034879972
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Summary : Research in the pharmaceutical industry today is in many respects quite different from what it used to be only fifteen years ago. There have been dramatic changes in approaches for identifying new chemical entities with a desired biological activity. While chemical modification of existing leads was the most important approach in the 1970s and 1980s, high-throughput screening and structure-based design are now major players among a multitude of methods used in drug discov ery. Quite often, companies favor one of these relatively new approaches over the other, e.g., screening over rational design, or vice versa, but we believe that an intelligent and concerted use of several or all methods currently available to drug discovery will be more successful in the medium term. What has changed most significantly in the past few years is the time available for identifying new chemical entities. Because of the high costs of drug discovery projects, pressure for maximum success in the shortest possible time is higher than ever. In addition, the multidisciplinary character of the field is much more pronounced today than it used to be. As a consequence, researchers and project managers in the pharmaceutical industry should have a solid knowledge of the more important methods available to drug discovery, because it is the rapidly and intelligently combined use of these which will determine the success or failure of preclinical projects.

Reducing Drug Attrition

Reducing Drug Attrition
  • Author : James R. Empfield,Michael P Clark
  • Publisher :Unknown
  • Release Date :2014-11-27
  • Total pages :162
  • ISBN : 9783662439142
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Summary : Medicinal chemistry is both science and art. The science of medicinal chemistry offers mankind one of its best hopes for improving the quality of life. The art of medicinal chemistry continues to challenge its practitioners with the need for both intuition and experience to discover new drugs. Hence sharing the experience of drug research is uniquely beneficial to the field of medicinal chemistry. Drug research requires interdisciplinary team-work at the interface between chemistry, biology and medicine. Therefore, the topic-related series Topics in Medicinal Chemistry covers all relevant aspects of drug research, e.g. pathobiochemistry of diseases, identification and validation of (emerging) drug targets, structural biology, drugability of targets, drug design approaches, chemogenomics, synthetic chemistry including combinatorial methods, bioorganic chemistry, natural compounds, high-throughput screening, pharmacological in vitro and in vivo investigations, drug-receptor interactions on the molecular level, structure-activity relationships, drug absorption, distribution, metabolism, elimination, toxicology and pharmacogenomics. In general, special volumes are edited by well known guest editors.

Designing Multi-Target Drugs

Designing Multi-Target Drugs
  • Author : J. Richard Morphy,C John Harris
  • Publisher :Unknown
  • Release Date :2012-03-28
  • Total pages :394
  • ISBN : 9781849734912
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Summary : 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.