Toxicogenomics

Early characterization of toxicity and efficacy would significantly impact the overall productivity of pharmaceutical R&D and reduce drug candidate attrition and failure. By describing the available platforms and weighing their relative advantages and disadvantages, including microarray data analysis, Genomics in Drug Discovery and Development introduces readers to the biomarker, pharmacogenomic, and toxicogenomics toolbox. The authors provide a valuable resource for pharmaceutical discovery scientists, preclinical drug safety department personnel, regulatory personnel, discovery toxicologists, and safety scientists, drug development professionals, and pharmaceutical scientists.

Tailored to the needs of scientists developing drugs, chemicals, cosmetics and other products this one-stop reference for medicinal chemists covers all the latest developments in the field of predictive toxicology and its applications in safety assessment. With a keen emphasis on novel approaches, the topics have been tackled by selected expert scientists, who are familiar with the theoretical scientific background as well as with the practical application of current methods. Emerging technologies in toxicity assessment are introduced and evaluated in terms of their predictive power, with separate sections on computer predictions and simulation methods, novel in vitro systems including those employing stem cells, toxicogenomics and novel biomarkers. In each case, the most promising methods are discussed and compared to classical in vitro and in vivo toxicology assays. Finally, an outlook section discusses such forward-looking topics as immunotoxicology assessment and novel regulatory requirements. With its wealth of methodological knowledge and its critical evaluation of modern approaches, this is a valuable guide for toxicologists working in pharmaceutical development, as well as in safety assessment and the regulation of drugs and chemicals.

Leading experts illustrate how sophisticated computational data mining techniques can impact contemporary drug discovery and development In the era of post-genomic drug development, extracting and applying knowledge from chemical, biological, and clinical data is one of the greatest challenges facing the pharmaceutical industry. Pharmaceutical Data Mining brings together contributions from leading academic and industrial scientists, who address both the implementation of new data mining technologies and application issues in the industry. This accessible, comprehensive collection discusses important theoretical and practical aspects of pharmaceutical data mining, focusing on diverse approaches for drug discovery—including chemogenomics, toxicogenomics, and individual drug response prediction. The five main sections of this volume cover: A general overview of the discipline, from its foundations to contemporary industrial applications Chemoinformatics-based applications Bioinformatics-based applications Data mining methods in clinical development Data mining algorithms, technologies, and software tools, with emphasis on advanced algorithms and software that are currently used in the industry or represent promising approaches In one concentrated reference, Pharmaceutical Data Mining reveals the role and possibilities of these sophisticated techniques in contemporary drug discovery and development. It is ideal for graduate-level courses covering pharmaceutical science, computational chemistry, and bioinformatics. In addition, it provides insight to pharmaceutical scientists, principal investigators, principal scientists, research directors, and all scientists working in the field of drug discovery and development and associated industries.

Covers powerful new tools for drug development Molecular pathology offers tools and techniques that can greatly enhance the drug discovery and development process, helping to make the promises of personalized medicine a reality. Molecular Pathology in Drug Discovery and Development provides an unmatched guide to this cutting-edge discipline and its applications to pharmaceutical science. With contributions from leading lights in drug discovery, drug development, and molecular pathology balanced by a consistent editorial approach, this reference offers both an overview of molecular pathology and a close look at the methods as they are applied to the process of drug discovery and development. Presented as steps in the drug development process, the coverage includes the use of molecular pathology to: Identify and validate new drug candidates Enhance transcriptional profiling to better find and validate biomarkers Assess toxicology Employ toxicogenomics to identify genes relevant to the safety of compounds Identify correct doses for different drugs Identify patients for treatment Develop molecular therapies Further the new techniques of Immunohistochemistry and Immunofluorescence With many tests and treatments already working today, drug research and development using molecular pathology has shown itself an extremely fruitful area. Molecular Pathology in Drug Discovery and Development gives practitioners an up-to-date resource on this highly active discipline and its role in furthering pharmaceutical research.

During the past decade it has become evident that microRNAs regulate gene expressions and control many developmental and cellular processes in eukaryotic organisms. Recent studies suggest that microRNAs play an important role in toxicogenomics and are likely to play an important role in a range of human diseases including cancer. microRNAs in Toxicology and Medicine is a comprehensive and authoritative compilation of up-to-date developments in this emerging research area, presented by internationally recognized investigators. It focuses on the role of microRNA in biology and medicine with a special emphasis on toxicology. Divided into six parts, topics covered include: microRNA and toxicology – including environmental toxicants and perturbation of miRNA signaling; microRNA, and Disease States featuring microRNAs in drug-induced liver toxicity, microRNAs and Inflammation the regulatory role of microRNA in mutagenesis, microRNAs and cancer, and the role of microRNAs in tumor progression and therapy, as well as current understanding of microRNAs as therapeutic targets in cancer microRNAs and disease states microRNAs and stem cells microRNAs and genomics microRNAs and epigenomics microRNAs and biomarkers – including body fluid microRNAs as toxicological biomarkers, cell-free microRNAs as biomarkers in human diseases, and circulating microRNAs as biomarkers of drug-induced pancreatitis microRNAs in Toxicology and Medicine is an essential insight into the current trends and future directions of research in this rapidly expanding field for investigators, toxicologists, risk assessors, and regulators in academia, medical settings, industry, and government.

Epigenetics is the study of both heritable and non-heritable changes in the regulation of gene activity and expression that occur without an alteration in the DNA sequence. This dynamic and rapidly developing discipline is making its impact across the biomedical sciences, in particular in toxicology where epigenetic differences can mean that different individuals respond differently to the same drug or chemical. Toxicology and Epigenetics reflects the multidimensional character of this emerging area of toxicology, describing cutting-edge molecular technologies to unravel epigenetic changes, the use of in vivo and in vitro models, as well as the potential use of toxicological epigenetics in regulatory environments. An international team of experts consider the interplay between epigenetics and toxicology in a number of areas, including environmental, nutritional, pharmacological, and computational toxicology, nanomaterials, proteomics and metabolomics, and cancer research. Topics covered include: environment, epigenetics and diseases DNA methylation and toxicogenomics chromatin at the intersection of disease and therapy epigenomic actions of environmental arsenicals environment, epigenetics and cardiovascular health toxicology, epigenetics and autoimmunity ocular epigenomics: potential sites of environmental impact in development and disease nuclear RNA silencing and related phenomena in animals epigenomics – impact for drug safety sciences methods of global epigenomic profiling transcriptomics: applications in epigenetic toxicology Toxicology and Epigenetics is an essential insight into the current trends and future directions of research in this rapidly expanding field for investigators, toxicologists, risk assessors and regulators in academia, industry and government.

A clear, straightforward resource to guide you through preclinical drug development Following this book's step-by-step guidance, you can successfully initiate and complete critical phases of preclinical drug development. The book serves as a basic,comprehensive reference to prioritizing and optimizing leads, toxicity, pharmacogenomics, modeling, and regulations. This single definitive, easy-to-use resource discusses all the issues that need consideration and provides detailed instructions for current methods and techniques. Each chapter was written by one or more leading experts in the field. These authors, representing the many disciplines involved in preclinical toxicology screening and testing, give you the tools needed to apply an effective multidisciplinary approach. The editor, with more than thirty years' experience working with pharmaceutical and biotechnology companies, carefully reviewed all the chapters to ensure that each one is thorough, accurate, and clear. Among the key topics covered are: * In vitro mammalian cytogenetics tests * Phototoxicity * Carcinogenicity studies * The pharmacogenomics of personalized medicine * Bridging studies * Toxicogenomics and toxicoproteomics Each chapter offers a full exploration of problems that may be encountered and their solutions. The authors also set forth the limitations of various methods and techniques used in determining the safety and efficacy of a drug during the preclinical stage. This is a hands-on guide for pharmaceutical scientists involved in preclinical testing,enabling them to perform and document preclinical safety tests to meet all FDA requirements before clinical trials may begin.

An essential resource for graduate students, academic and industrial toxicologists, and environmental health scientists and professionals Over the course of thirty years and three editions, Introduction to Biochemical Toxicology has been an important source for coverage of the ongoing quest to define the biochemical, cellular, and molecular events induced by toxicants at the cellular and organismic levels. Now, as the principles and methods of molecular and cellular biology as well as genomic sciences play an ever increasing role in mechanistic toxicology, significant changes have been made to the book, resulting in this important new edition-now titled Molecular and Biochemical Toxicology, Fourth Edition. Much more than an introductory text, this crucial new edition has been completely revised to provide timely and thorough coverage of the underlying biochemical, molecular, and cellular mechanisms through which toxicants produce their adverse effects. Toxicological issues are covered from the molecule to the cell to the organ level. Complex methods used in toxicology are also described in a straightforward, easy-to-understand style. Additional features of this new edition include: New chapters that explore the interface between toxicology and genomic sciences, including: bioinformatics, proteomics, metabolomics, and toxicogenomics Increased emphasis on structure, mechanism, and regulation of xenobiotic metabolizing enzymes, toxicogenetics, and xenobiotic transporters Additional new chapters on: molecular epidemiology and genetic susceptibility, DNA damage and mutagenesis, DNA repair, mechanisms of cell death, mitochondrial dysfunction, metals, reproductive toxicology, developmental toxicology, and reactive oxygen/metabolites and toxicity Molecular and Biochemical Toxicology, Fourth Edition guides graduate students, toxicologists, and environmental health professionals through the principles of molecular and biochemical toxicology and the complex mechanisms of toxicity. Whether it's used in the classroom or in industry, research, or academia, this book is essential for anyone interested in understanding the molecular mechanisms through which toxicants produce adverse effects.