Wiley in Drug Discovery and Development

A comprehensive resource on case studies of marketed kinase drugs and promising drug trials Since the discovery of protein kinase activity in 1954, the field of protein kinase drug discovery has advanced dramatically. With the ongoing clinical success of the Bcr-Abl kinase inhibitor Gleevec in the treatment of chronic myelogenous leukemia and seven additional marketed kinase inhibitor drugs, researchers have compelling evidence that kinase inhibitors can be highly efficacious in the treatment of diseases caused by aberrant activity of protein kinase. Currently more than 100 protein kinase inhibitors are in clinical development. In one comprehensive volume, the editors, Dr. Rongshi Li and Dr. Jeffrey Stafford, present timely and important case studies of marketed kinase drugs and several of the most advanced kinase inhibitors in clinical trials. Kinase Inhibitor Drugs includes: • Case studies from leading investigators and experts in the field that provide firsthand accounts of kinase inhibitor discovery • Current thinking on kinase structure, biochemistry, and signal transduction pathways • Information on state-of-the-art technologies and tools such as structure-based and fragment-based drug discovery • A lineup of clinical-phase growth factor receptor inhibitors • Inhibitors of cell cycle kinases • The discovery of allosteric inhibitors of MEK kinase • Information on pharmacogenomics and its application to kinase inhibitor clinical development

This book contains contributions from interdisciplinary scientists to collectively address the issue of targeting carbohydrate recognition for the development of novel therapeutic and diagnostic agents. The book covers (1) biological problems involving carbohydrate recognition, (2) structural factors mediating carbohydrate recognition, (3) design and synthesis of lectin mimics that recognize carbohydrate ligands with high specificity and affinity, and (4) modulation of biological and pathological processes through carbohydrate recognition.

A thorough, accessible, and general overview of chemosensors Providing a comprehensive overview of chemosensors-organic molecules designed to bind and sense small molecules or metal ions-and their applications, “Chemosensors: Principles, Strategies, and Applications” is an accessible one-stop resource for analysts, clinicians, and graduate students studying advanced chemistry and chemosensing. Chemosensors function on a molecular level, generating a signal upon binding. The book reviews their synthesis, design, and applications for detecting biological and organic molecules as well as metal ions. The text highlights applications in drug discovery and catalyses that have not been well covered elsewhere. Covering such topics as molecular recognition, detection methods, design strategies, and important biological issues, the book is broken into four sections that examine intermolecular interactions, strategies in sensor design, detection methods, and case studies in metal, saccharide, and amino acid sensing. An indispensable source of information for chemical and biomedical experts using sensors, Chemosensors includes case studies to make the material both accessible and understandable to chemists of all backgrounds.

Understand and assess the design, delivery, and efficacy of orally administered drugs A practical guide to understanding oral bioavailability, one of the major hurdles in drug development and delivery, Oral Bioavailability: Basic Principles, Advanced Concepts, and Applications is designed to help chemists, biologists, life science researchers, pharmaceutical scientists, pharmacologists, clinicians, and graduate and students become familiar with the fundamentals and practices of the science of oral bioavailability. The difference in rate and extent between a drug taken orally and the actual amount of a drug reaching the circulatory system, oral bioavailability is an essential parameter for determining the efficacy and adverse effects of new and developing medications, as well as finding an optimal dosing regimen. This book provides a much-needed one-stop resource to help readers better understand and appreciate the many facets and complex problems of oral bioavailability, including the basic barriers to oral bioavailability, the methods used to determine relevant parameters, and the challenges of drug delivery. In addition, this comprehensive book discusses biological and physicochemical methods for improving bioavailability, integrates physicochemistry with physiology and molecular biology, and includes several state-of-the-art technologies and approaches-Caco-2 cell culture model, MDCK, and other related cell culture models-which are used to study the science of oral bioavailability.

Complete, up-to-date coverage of the broad area of nucleic acid chemistry and biology. Assembling contributions from a collection of authors with expertise in all areas of nucleic acids, medicinal chemistry, and therapeutic applications, “Medicinal Chemistry of Nucleic Acids” presents a thorough overview of nucleic acid chemistry-a rapidly evolving and highly challenging discipline directly responsible for the development of antiviral and antitumor drugs. This reliable resource delves into a multitude of subject areas involving the study of nucleic acids-such as the new advances in genome sequencing, and the processes for creating RNA interference (RNAi) based drugs-to assist pharmaceutical researchers in removing roadblocks that hinder their ability to predict drug efficacy. Offering the latest cutting-edge science in this growing field, “Medicinal Chemistry of Nucleic Acids” includes: • In-depth coverage of the development and application of modified nucleosides and nucleotides in medicinal chemistry • A close look at a large range of current topics on nucleic acid chemistry and biology • Essential information on the use of nucleic acid drugs to treat diseases like cancer • A thorough exploration of siRNA for RNAi and the regulation of microRNA, non-coding RNA (ncRNA), a newly developing and exciting research area Thorough in its approach and promising in its message, “Medicinal Chemistry of Nucleic Acids” probes the new domains of pharmaceutical research-and exposes readers to a wealth of new drug discovery opportunities emerging in the dynamic field of nucleic acid chemistry.

An in-depth exploration of the applications of plant bioactive metabolites in drug research and development Highlighting the complexity and applications of plant bioactive metabolites in organic and medicinal chemistry, Plant Bioactives and Drug Discovery: Principles, Practice, and Perspectives provides an in-depth overview of the ways in which plants can inform drug research and development. An edited volume featuring multidisciplinary international contributions from acclaimed scientists researching bioactive natural products, the book provides an incisive overview of one of the most important topics in pharmaceutical studies today. With coverage of strategic methods of natural compound isolation, structural manipulation, natural products in clinical trials, quality control, and more, and featuring case studies on medicinal plants, the book serves as a definitive guide to the field of plant biodiversity as it relates to medicine. In addition, chapters on using natural products as drugs that target specific disease areas, including neurological disorders, inflammation, infectious diseases, and cancer, illustrate the myriad possibilities for therapeutic applications. Wide ranging and comprehensive, Plant Bioactives and Drug Discovery also includes important information on marketing, regulations, intellectual property rights, and academic-industry collaboration as they relate to plant-based drug research, making it an essential resource for advanced students and academic and industry professionals working in biochemical, pharmaceutical, and related fields.

The opportunities and challenges of using dendrimers to improve drug delivery. Among pharmaceutical and biomedical researchers, the use of dendrimers in drug delivery systems has attracted increasing interest. In particular, researchers have noted that the volume of a dendrimer increases when it has a positive charge. If this property can be applied effectively, dendrimers have enormous potential in drug delivery systems, directly supplying medication to targeted human organs. With contributions from an international team of pioneers and experts in dendrimer research, this book provides a comprehensive overview of the latest research efforts in designing and optimizing dendrimer-based drug delivery systems. The book analyzes key issues, demonstrating the critical connections that link fundamental concepts, design, synthesis, analytical methodology, and biological assessment to the practical use of dendrimers in drug delivery applications. Topics covered include: • Dendrimer history • Synthesis • Physicochemical properties • Principles of drug delivery • Applications in diverse biomedical fields “Dendrimer-Based Drug Delivery Systems” reflects the authors' thorough review and analysis of the current literature as well as their own firsthand experience in the lab. Readers will not only discover the current state of the science, but also gain valuable insights into fruitful directions for future research. References at the end of each chapter serve as a gateway to the growing body of literature in the field, enabling readers to explore each individual topic in greater depth. Pharmaceutical and biomedical researchers will find this book a unique and essential guide to the opportunities, issues, and challenges involved in fully exploiting the potential of dendrimers to improve drug delivery.

This book reviews advances in understanding phosphodiesterases within the central nervous system and their therapeutic applications. A range of expert authors from both academia and industry describe these, then focus on the areas of greatest scientific and medical interest to provide more detailed coverage. Therapeutic and drug discovery applications are covered for diseases including Alzheimer's, Parkinson's, schizophrenia, erectile dysfunction, and spinal cord injuries. There is also a chapter on drug discovery tools such as in vitro assays and X-ray structures for medicinal chemistry studies.

ORAL BIOAVAILABILITY AND DRUG DELIVERY Improve the performance and viability of newly-developed and approved drugs with this crucial guide Bioavailability is the parameter which measures the rate and extent to which a drug reaches a user's circulatory system depending on the method of administration. For example, intravenous administration produces a bioavailability of 100%, since the drugs are injected directly into the circulatory system; in the case of oral administration, however, bioavailability can vary widely based on factors which, if not properly understood, can result in a failure in drug development, adverse effects, and other complications. The mechanics of oral bioavailability are therefore critical aspects of drug development. Oral Bioavailability and Drug Delivery provides a comprehensive coverage of this subject as well as its drug development applications. Beginning with basic terminology and fundamental concepts, it provides a thorough understanding of the challenges and barriers to oral bioavailability as well as the possibilities for improving this parameter. The resulting book is an indispensable tool for drug development research. Oral Bioavailability and Drug Delivery readers will also find: • Discussion questions in many chapters to facilitate comprehension • Detailed discussion of topics including dissolution, absorption, metabolism, and more • Real-world examples of methods in actions throughout Oral Bioavailability and Drug Delivery is ideal for pharmaceutical and biotechnology scientists working in drug discovery and development; researchers in chemistry, biology, pharmacology, immunology, neuroscience, and other related fields; and graduate courses in drug development and delivery.

HYDROGEN SULFIDE Covers H2S interactions, methods of detection and delivery in biological environments, and a wide range of applications. Research on hydrogen sulfide (H2S) spans diverse disciplines including chemistry, biology, and physiology. In recent years, new materials and approaches have been developed to deliver H2S and related reactive sulfur species in various clinical contexts. Although many biological pathways involving H2S are complex, all are governed by fundamental chemical interactions between reactive sulfur species and other molecular entities. “Hydrogen Sulfide: Chemical Biology Basics, Detection Methods, Therapeutic Applications, and Case Studies” provides the foundation required for understanding the fundamental chemical biology of H2S while highlighting the compound's therapeutic potential and medicinal applications. This book covers key aspects of H2S chemical biology, including the fundamental chemistry of reactive sulfur species; the measurement, detection, and delivery of H2S in biological environments; and the therapeutic and medicinal uses of exogenous H2S delivery in various pharmacologically relevant systems. Throughout the text, editor Michael Pluth and chapter contributors discuss the opportunities and future of the multidisciplinary field. • Provides approaches for delivering H2S with relevance to biological and therapeutic applications • Describes complex interactions of H2S with bioinorganic complexes and reactive sulfur, nitrogen, and oxygen species • Summarizes advances in available tools to detect, measure, and modulate H2S levels in biological environments, such as real-time methods for H2S fluorescence imaging in live cell and animal systems • Helps readers understand known systems and make connections to new and undiscovered pathways and mechanisms of action • Includes in-depth case studies of different systems in which H2S plays an important role “Hydrogen Sulfide: Chemical Biology Basics, Detection Methods, Therapeutic Applications, and Case Studies” is an important source of current knowledge for researchers, academics, graduate students, and industrial scientists in the fields of redox biology, hydrogen sulfide research, and medicinal chemistry of small biological molecules.

An up-to-date and comprehensive exploration of nucleic acid medicinal chemistry and its applications In “Nucleic Acids in Medicinal Chemistry and Chemical Biology: Drug Development and Clinical Applications”, a team of distinguished researchers delivers a comprehensive overview of the chemistry and biology of nucleic acids and their therapeutic applications. The book emphasizes the latest research in the field, including new technologies like CRISPR that create novel possibilities to edit mutated genes at the genomic DNA level and to treat inherited diseases and cancers. The authors explore the application of modified nucleosides and nucleotides in medicinal chemistry, a variety of current topics on nucleic acid chemistry and biology, nucleic acid drugs used to treat disease, and more. They also probe new domains of pharmaceutical research, offering the reader a wealth of new drug discovery opportunities emerging in this dynamic field. Readers will also find: • A thorough introduction to the basic terminology and knowledge of the field of nucleic acid medicinal chemistry • Comprehensive explorations of the methods used to determine the development of nucleic acid drugs • Practical discussions of new technologies, like CRISPR, nanotechnology-based delivery systems, synthetic biology, and DNA-encoded chemical libraries • In-depth examinations of the latest, cutting-edge developments in nucleic acid medicinal chemistry Perfect for medicinal and nucleic acid chemists, “Nucleic Acids in Medicinal Chemistry and Chemical Biology” will also earn a place in the libraries of biochemists, chemical biologists, and pharmaceutical researchers.

Drug transporter fundamentals and relevant principles and techniques, featuring new and expanded chapters. “Drug Transporters: Molecular Characterization and Role in Drug Disposition” provides in-depth analysis of the conceptual evolution and technical development for studying drug transporters. Contributions by an international panel of leading researchers address advances in transporters as drug targets, transporters in pharmacotherapy, the impact of transporters on drug efficacy and safety, the development of sophisticated model systems and sensitive assay methods, and more. Divided into two parts, the book first provides a thorough overview of relevant drug transporters before detailing the principles of drug transport and associated techniques. The updated and expanded third edition includes new chapters on in vitro-in vivo scale-up of drug transport activities, the ontogeny of drug transporters, the application of physiologically-based pharmacokinetic and pharmacodynamic modeling, and the use of transporters as therapeutic targets for diseases. • Reflects the current state of the field and offers perspectives on future directions • Covers basic knowledge, clinical outcomes, and emerging discoveries in transporter science • Provides up-to-date information on drug transporter families, mechanisms, and clinical implications • Includes extensive references and numerous figures and tables throughout Understandable for novices while offering sufficient depth for more experienced researchers, “Drug Transporters: Molecular Characterization and Role in Drug Disposition”, Third Edition is an excellent textbook for pharmacological or physiological science courses in drug/membrane transport, and an invaluable reference for academic or industrial scientists working in the transporter field and related areas of drug metabolism, pharmacokinetics, and pharmacodynamics.

An insightful reference for the latest physiological and therapeutic studies of carbon monoxide. In “Carbon Monoxide in Drug Discovery: Basics, Pharmacology, and Therapeutic Potential”, a team of distinguished authors delivers foundational knowledge, the latest research, and remaining challenges regarding the physiological roles and therapeutic efficacy of carbon monoxide (CO). The editors have included a broad selection of resources from leading experts in the field that discuss the background and physiological roles of CO, a variety of delivery forms including CO prodrugs using benign carriers, CO sensing, therapeutic applications, and clinical trials. Organized by topic to allow each chapter to be read individually, the book covers a wide range of topics, from physiological and patho-physiological mechanisms at the molecular level to clinical applications for multiple disease processes. The editors of “Carbon Monoxide in Drug Discovery” have created a compelling argument for shifting the accepted understanding of CO from poison to bioactive molecule with enormous clinical benefits. Readers will also benefit from: • A thorough introduction to the background and physiological actions of carbon monoxide, including endogenous CO production in sickness and in health • Comprehensive explorations of CO delivery forms, including non-carrier formulations, metal-carbonyl complexes, and organic CO donors • Practical discussions of carbon monoxide sensing and scavenging, including fluorescent probes for intracellular carbon monoxide detection • In-depth examinations of the therapeutic applications of CO, including CO in solid organ transplantation Perfect for professors, graduate students, and postdocs in the fields of biology, pharmacology, immunology, medicinal chemistry, toxicology, and drug delivery, “Carbon Monoxide in Drug Discovery: Basics, Pharmacology, and Therapeutic Potential” is also an invaluable resource for industrial scientists in these areas.

Following its successful predecessor, this book covers the fundamentals, delivery routes and vehicles, and practical applications of drug delivery. In the 2nd edition, almost all chapters from the previous are retained and updated and several new chapters added to make a more complete resource and reference. • Helps readers understand progress in drug delivery research and applications • Updates and expands coverage to reflect advances in materials for delivery vehicles, drug delivery approaches, and therapeutics • Covers recent developments including transdermal and mucosal delivery, lymphatic system delivery, theranostics • Adds new chapters on nanoparticles, controlled drug release systems, theranostics, protein and peptide drugs, and biologics delivery

This book comprehensively covers the mechanisms of action and inhibitor design for HIV-1 integrase. It serves as a resource for scientists facing challenging drug design issues and researchers in antiviral drug discovery. Despite numerous review articles and isolated book chapters dealing with HIV-1 integrase, there has not been a single source for those working to devise anti-AIDS drugs against this promising target. But this book fills that gap and offers a valuable introduction to the field for the interdisciplinary scientists who will need to work together to design drugs that target HIV-1 integrase.