Biomarkers in Drug Development. A Handbook of Practice, Application, and Strategy

The essentials of drug metabolism vital to developing new therapeutic entities Information on the metabolism and disposition of candidate drugs is a critical part of all aspects of the drug discovery and development process. Drug metabolism, as practiced in the pharmaceutical industry today, is a complex, multidisciplinary field that requires knowledge of sophisticated analytical technologies and expertise in mechanistic and kinetic enzymology, organic reaction mechanism, pharmacokinetic analysis, animal physiology, basic chemical toxicology, preclinical pharmacology, and molecular biology. With chapters contributed by experts in their specific areas, this reference covers: * Basic concepts of drug metabolism * The role of drug metabolism in the pharmaceutical industry * Analytical techniques in drug metabolism * Common experimental approaches and protocols Drug Metabolism in Drug Design and Development emphasizes practical considerations such as the data needed, the experiments and analytical methods typically employed, and the interpretation and application of data. Chapters highlight facts, common protocols, detailed experimental designs, applications, and limitations of techniques. This is a comprehensive, hands-on reference for drug metabolism researchers as well as other professionals involved in pre-clinical drug discovery and development.

This book provides an introduction to the field of biomarkers, how they have been and can be used, and how different approaches can be used to identify, characterize, and monitor biomarkers. The book has chapters on topics including HIV, Cancer, Parkinson’s, vascular injury, environmental exposure. A following section discusses the technologies (diagnostics and assays) to detect biomarkers and authors have emphasized the preclinical and clinical manifestation of the injury/disease process.

Lipases and Phospholipases are key control elements in mammalian metabolism. They share many common features that set them apart from other metabolic enzyme classes, most importantly their association with biological membranes. Their potential as drug targets for the treatment of metabolic diseases is widely recognized, and the first lipase inhibitor drugs have been successfully introduced. Providing drug developers with a firm foundation for lipase-centered drug design, the editors of this volume have assembled experts from different scientific disciplines to create a comprehensive handbook for all pharmaceutical chemists, biochemists and physiologists working with lipases. The authors examine fundamental aspects of lipase function in vitro and in vivo, explaining how this knowledge may be used to develop lipase assays. They also treat the physiological roles of lipases in normal and disordered metabolism, as well as strategies to target lipases for the treatment of diabetes, obesity and related disorders. Additional topics include the application of phospholipases for liposome-based drug delivery and their use as diagnostic tools.

This book covers the unique application of flow cytometry in drug discovery and development. The first section includes two introductory chapters, one on flow cytometry and one on biomarkers, as well as a chapter on recent advances in flow cytometry. The second section focuses on the unique challenges and added benefits associated with the use of flow cytometry in the drug development process. The third section contains a single chapter presenting an in depth discussion of validation considerations and regulatory compliance issues associated with drug development.

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.

Practical Utility of Biomarkers in Drug Discovery and Development covers all aspects of biomarker research applied to drug discovery and development and contains state-of-the-art appraisals on the practical utility of genomic, biochemical, and protein biomarkers. Case histories and lessons from successful and unsuccessful applications of biomarkers are included along with key chapters on GLP validation, safety biomarkers and proteomics biomarkers. Regulatory agency perspectives and initiatives both in the US and internationally are also discussed.

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.

CONTEMPORARY ACCOUNTS IN DRUG DISCOVERY AND DEVELOPMENT A useful guide for medicinal chemists and pharmaceutical scientists Drug discovery is a lengthy and complex process that typically involves identifying an unmet medical need, determining a biological target, chemical library screening to identify a lead, chemical optimization, preclinical studies and clinical trials. This process often takes many years to complete, and relies on practitioners’ knowledge of chemistry and biology, but also—and perhaps more importantly—on experience. Improving the success rate in discovery and development through a thorough knowledge of drug discovery principles and advances in technology is critical for advancement in the field. Contemporary Accounts in Drug Discovery and Development provides drug discovery scientists with the knowledge they need to quickly gain mastery of the drug discovery process. A thorough accounting is given for each drug covered within the book, as the authors provide pharmacology, drug metabolism, biology, drug development, and clinical studies for every case, with modern drug discovery principles and technologies incorporated throughout. Contemporary Accounts in Drug Discovery and Development readers will also find Case histories used as an engaging way of learning about the drug discovery/development process Detailed biological rational and background information, drug design principles, SAR development, ADMET considerations, and clinical studies The full history of individual marketed small molecule drugs Coverage of drug candidates that have passed Phase I clinical trials with different modalities, such as antibody drug conjugates (ADC), proteolysis-targeting chimera (PROTAC), and peptide drugs The application of new technologies in drug discovery such as DNA-encoded libraries (DEL), positron emission tomography (PET), and physics-based computational modeling employing free energy perturbation (FEP) Contemporary Accounts in Drug Discovery and Development is a helpful tool for medicinal chemists, organic chemists, pharmacologists, and other scientists in drug research and process development. It may be considered essential reading for graduate courses in drug discovery, medicinal chemistry, drug synthesis, pharmaceutical science, and pharmacology. It is also a useful resource for pharmaceutical industry labs, as well as for libraries.

Drug-Drug Interactions in Pharmaceutical Development comprehensively reviews the relevant science, industrial practice, and regulatory agency positions on drug-drug interactions. It focuses on the evaluation of potential drug-drug interactions, allowing researchers to address risk factors before a drug is put to market. The book covers both clinical and nonclinical aspects for understanding drug-drug interactions as well as in vitro and in vivo studies for use in studying interactions at the drug discovery stage.