This book reviews the principles of design and examples of successful implementation of proteinkinase inhibitors (PKI), and offers a comprehensive and authoritative overview of the history and latest developments in the field. Chapters written by experts from industry and academia cover the function, structure and topology of Proteinkinases, molecular modelling, disclose how to achieve high level of selectivity for kinase inhibitors, and exploit kinase inhibitors for cancer treatment. Particular attention is given to Inhibitors of c-Jun N-terminal kinase 3, and to covalent Janus Kinase 3 Inhibitors. A case study on Receptor Tyrosine Kinases EGFR, VEGFR, PDGFR is also presented in this book. Given its breath, this book will appeal to medicinal chemists, students, researchers and professionals alike.

The purpose of this book, which is written mainly for pharmacothera pists, is to draw the physician's attentions, through specific examples, to iatrogenic (i.e., diagnostically or therapeutically induced) carcino genesis. The book is not intended, however, to arouse public concern. It has been known for some time that each therapeutic measure has a risk-benefit ratio, the estimation of which requires an understanding of carcinogenic side-effects. The number of iatrogenic tumors published so far is not large; however, we assume that there are a number of cases that have not been registered. In the past it was not generally recognized that medical treatment might involve carcinogenic risks; moreover, various therapeutic measures are often used simultaneously so that it may be difficult to trace the cause of tumor formation to a specific agent. Animal experiments and clinical observations during the past few years have contributed to our knowledge of the possible hazards of drugs. We have compiled the most important literature on the subject without, however, attempting completion. The present book may help the pharmacotherapist balance the benefit of a drug against its potential risk, and is thus consistent with the medical principle of nil nocere. We thank Mrs. M. Gomille (Institut fur Toxikologie und Chemothera pie, Deutsches Krebsforschungszentrum, Heidelberg) for her help in the preparation of the manuscript.

A comprehensive look at existing technologies and processes for continuous manufacturing of pharmaceuticals As rising costs outpace new drug development, the pharmaceutical industry has come under intense pressure to improve the efficiency of its manufacturing processes. Continuous process manufacturing provides a proven solution. Among its many benefits are: minimized waste, energy consumption, and raw material use; the accelerated introduction of new drugs; the use of smaller production facilities with lower building and capital costs; the ability to monitor drug quality on a continuous basis; and enhanced process reliability and flexibility. Continuous Manufacturing of Pharmaceuticals prepares professionals to take advantage of that exciting new approach to improving drug manufacturing efficiency. This book covers key aspects of the continuous manufacturing of pharmaceuticals. The first part provides an overview of key chemical engineering principles and the current regulatory environment. The second covers existing technologies for manufacturing both small-molecule-based products and protein/peptide products. The following section is devoted to process analytical tools for continuously operating manufacturing environments. The final two sections treat the integration of several individual parts of processing into fully operating continuous process systems and summarize state-of-art approaches for innovative new manufacturing principles. * Brings together the essential know-how for anyone working in drug manufacturing, as well as chemical, food, and pharmaceutical scientists working on continuous processing * Covers chemical engineering principles, regulatory aspects, primary and secondary manufacturing, process analytical technology and quality-by-design * Contains contributions from researchers in leading pharmaceutical companies, the FDA, and academic institutions * Offers an extremely well-informed look at the most promising future approaches to continuous manufacturing of innovative pharmaceutical products Timely, comprehensive, and authoritative, Continuous Manufacturing of Pharmaceuticals is an important professional resource for researchers in industry and academe working in the fields of pharmaceuticals development and manufacturing.

From its origins as a niche technique more than 15 years ago, fragment-based approaches have become a major tool for drug and ligand discovery, often yielding results where other methods have failed. Written by the pioneers in the field, this book provides a comprehensive overview of current methods and applications of fragment-based discovery, as well as an outlook on where the field is headed. The first part discusses basic considerations of when to use fragment-based methods, how to select targets, and how to build libraries in the chemical fragment space. The second part describes established, novel and emerging methods for fragment screening, including empirical as well as computational approaches. Special cases of fragment-based screening, e. g. for complex target systems and for covalent inhibitors are also discussed. The third part presents several case studies from recent and on-going drug discovery projects for a variety of target classes, from kinases and phosphatases to targeting protein-protein interaction and epigenetic targets.

Demonstrating how and why to measure physicochemical and biomimetic properties in early stages of drug discovery for lead optimization, Physicochemical and Biomimetic Properties in Drug Discovery encourages readers to discover relationships between various measurements and develop a sense of interdisciplinary thinking that will add to new research in drug discovery. This practical guide includes detailed descriptions of state-of-the-art chromatographic techniques and uses real-life examples and models to help medicinal chemists and scientists and advanced graduate students apply measurement data for optimal drug discovery.

This text offers in-depth perspectives on every aspect of protein structure identification, assessment, characterization, and utilization, for a clear understanding of the diversity of protein shapes, variations in protein function, and structure-based drug design. The authors cover numerous high-throughput technologies as well as computational methods to study protein structures and residues. A valuable reference, this book reflects current trends in the effort to solve new structures arising from genome initiatives, details methods to detect and identify errors in the prediction of protein structural models, and outlines challenges in the conversion of routine processes into high-throughput platforms.

Providing a roadmap from early to late stages of drug development, this book overviews amorphous solid dispersion technology - a leading platform to deliver poorly water soluble drugs, a major hurdle in today's pharmaceutical industry. - Helps readers understand amorphous solid dispersions and apply techniques to particular pharmaceutical systems - Covers physical and chemical properties, screening, scale-up, formulation, drug product manufacture, intellectual property, and regulatory considerations - Has an appendix with structure and property information for polymers commonly used in drug development and with marketed drugs developed using the amorphous sold dispersion approach - Addresses global regulatory issues including USA regulations, ICH guidelines, and patent concerns around the world

Since the publication of the first edition of Pharmaceutical Biotechnology over a decade ago, a not-so-subtle shift in the meaning of the term "biotechnology" has occurred. It has come to mean something very specific, namely the development of drug substances with large protein and polypeptide molecules. These substances can be used as drugs in their own right but may also be used to manipulate cellular DNA in order to produce a required molecule that is believed to have desirable properties in the treatment of a disease. Accordingly, the second edition of this popular text reflects that change of definition by including new material that explores the development of these protein-based therapeutic substances. See what's new in the Second Edition: Expanded coverage of the formulation of proteins Additional information on proteins used as drug delivery systems Detailed discussion of interactions between proteins and phospholipids Increased information on proteomics and gene therapy Exploration of pulmonary administration and oral delivery of proteins A broad review of vaccines Discussion of genetic engineering and genomics Challenges and issues involved in the development and the production of a drug

Parenteral Medications is an authoritative, comprehensive reference work on the formulation and manufacturing of parenteral dosage forms, effectively balancing theoretical considerations with practical aspects of their development. Previously published as a three-volume set, all volumes have been combined into one comprehensive publication that addresses the plethora of changes in the science and considerable advances in the technology associated with these products and routes of administration. Key Features: Provides a comprehensive reference work on the formulation and manufacturing of parenteral dosage forms Addresses changes in the science and advances in the technology associated with parenteral medications and routes of administration Includes 13 new chapters and updated chapters throughout Contains the contributors of leading researchers in the field of parenteral medications Uses full color detailed illustrations, enhancing the learning process The fourth edition not only reflects enhanced content in all the chapters but also highlights the rapidly advancing formulation, processing, manufacturing parenteral technology including advanced delivery and cell therapies. The book is divided into seven sectionss: Section 1 - Parenteral Drug Administration and Delivery Devices; Section 2 - Formulation Design and Development; Section 3 - Specialized Drug Delivery Systems; Section 4 - Primary Packaging and Container Closure Integrity; Section 5 - Facility Design and Environmental Control; Section 6 - Sterilization and Pharmaceutical Processing; Section 7 - Quality Testing and Regulatory Requirements

Polymers are one of the most fascinating materials of the present era finding their applications in almost every aspects of life. Polymers are either directly available in nature or are chemically synthesized and used depending upon the targeted applications.Advances in polymer science and the introduction of new polymers have resulted in the significant development of polymers with unique properties. Different kinds of polymers have been and will be one of the key in several applications in many of the advanced pharmaceutical research being carried out over the globe. This 4-partset of books contains precisely referenced chapters, emphasizing different kinds of polymers with basic fundamentals and practicality for application in diverse pharmaceutical technologies. The volumes aim at explaining basics of polymers based materials from different resources and their chemistry along with practical applications which present a future direction in the pharmaceutical industry. Each volume offer deep insight into the subject being treated. Volume 1: Structure and Chemistry Volume 2: Processing and Applications Volume 3: Biodegradable Polymers Volume 4: Bioactive and Compatible Synthetic/Hybrid Polymers

The legislative requirement for cannabis to undergo laboratory testing has followed legalization of medical and recreational use in every U.S. state to date. Cannabis safety testing is a new investment opportunity within the emerging cannabis market that is separate from cultivation, processing, and distribution, allowing individuals and organizations who may have been reluctant to enter previously a new entry route to the cannabis space. However, many of the costs, timelines, operational requirements, and compliance issues are overlooked by people who have not been exposed to regulated laboratory testing. Cannabis Laboratory Fundamentals provides an in-depth review of the key issues that impact cannabis testing laboratories and provides recommendations and solutions to avoid common - but expensive - mistakes. The text goes beyond methodology to include sections on economics, regulation, and operational challenges, making it useful for both new and experienced cannabis laboratory operators, as well as all those who want to understand the opportunities and risks of this industry.

In the quest for innovative drug delivery systems attempting to meet the unmet needs in pharmaceutical space, research has taken a much more complicated path that poses a significant challenge for translation. Despite the progress made with novel materials, polyesters still remain at the helm of drug delivery technologies. This book provides a single source of reference of polyester drug delivery systems that covers a broad spectrum of materials design, manufacturing techniques, and applications.

This book comprehensively describes the development and practice of DNA-encoded library synthesis technology. Together, the chapters detail an approach to drug discovery that offers an attractive addition to the portfolio of existing hit generation technologies such as high-throughput screening, structure-based drug discovery and fragment-based screening. The book: Provides a valuable guide for understanding and applying DNA-encoded combinatorial chemistry Helps chemists generate and screen novel chemical libraries of large size and quality Bridges interdisciplinary areas of DNA-encoded combinatorial chemistry synthetic and analytical chemistry, molecular biology, informatics, and biochemistry Shows medicinal and pharmaceutical chemists how to efficiently broaden available chemical space for drug discovery Provides expert and up-to-date summary of reported literature for DNA-encoded and DNA-directed chemistry technology and methods

Numerous phenomenal advances have been made towards understanding the role of neurotransmitters in the pathophysiology of neurological disorders, and these have resulted in a large number of novel molecules with the potential to revolutionize the treatment and prevention of such disorders. This book provides a comprehensive and detailed explanation of brain neurotransmitters and their receptors and associated channels. It includes a basic introduction, and also discusses the functions and recent advances and their pharmacology, highlighting the role of various computer aided drug design (CADD) strategies for the development of therapeutic ligands to modulate these receptors/ion channels. Written in an easy-to-read style, it is intended for neuroscience and pharmaceutical students and researchers working in the area of brain neurotransmitters.

Enables researchers to fully realize the potential to discover new pharmaceuticals among heterocyclic compounds

Integrating heterocyclic chemistry and drug discovery, this innovative text enables readers to understand how and why these two fields go hand in hand in the effective practice of medicinal chemistry. Contributions from international leaders in the field review more than 100 years of findings, explaining their relevance to contemporary drug discovery practice. Moreover, these authors have provided plenty of practical guidance and tips based on their own academic and industrial laboratory experience, helping readers avoid common pitfalls.

"Heterocyclic Chemistry in Drug Discovery" is ideal for readers who want to fully realize the almost limitless potential to discover new and effective pharmaceuticals among heterocyclic compounds, the largest and most varied family of organic compounds. The book features: Several case studies illustrating the role and application of 3, 4, 5, and 6+ heterocyclic ring systems in drug discoveryStep-by-step descriptions of synthetic methods and practical techniquesExamination of the physical properties for each heterocycle, including NMR data and quantum calculationsDetailed explanations of the complexity and intricacies of reactivity and stability for each class of heterocycles

"Heterocyclic Chemistry in Drug Discovery" is recommended as a textbook for organic and medicinal chemistry courses, particularly those emphasizing heterocyclic chemistry. The text also serves as a guide for medicinal and process chemists in the pharmaceutical industry, offering them new insights and new paths to explore for effective drug discovery.

Chitosan in Drug Delivery provides thorough insights into chitosan chemistry, collection, chemical modifications, characterization and applications in the pharmaceutical industry and healthcare fields. The book explores molecular weight, degree of deacetylation and molecular geometry, emphasizing recent advances in the field as written by academic, industry and regulatory scientists. It will be a useful resource for pharmaceutical scientists, including industrial pharmacists, analytical scientists, postgraduate students, health care professionals and regulatory scientists actively involved in pharmaceutical product and process development in natural polymers containing drug delivery.

Biopharmaceuticals are emerging as frontline medicines to combat several life-threatening and chronic diseases. However, such medicines are expensive to develop and produce on a commercial scale, contributing to rising healthcare costs. Developability of Biotherapeutics: Computational Approaches describes applications of computational and molecular modeling techniques that improve the overall process of discovery and development by removing empiricism. The concept of developability involves making rational choices at the pre-clinical stages of biopharmaceutical drug development that could positively impact clinical outcomes. The book also addresses a general lack of awareness of the many different contributions that computation can make to biopharmaceutical drug development. This informative and practical reference is a valuable resource for professionals engaged in industrial research and development, scientists working with regulatory agencies, and pharmacy, medicine, and life science students and educators. It focuses primarily on the developability of monoclonal antibody candidates, but the principles described can also be extended to other modalities such as recombinant proteins, fusion proteins, antibody drug conjugates and vaccines. The book is organized into two sections. The first discusses principles and applications of computational approaches toward discovering and developing biopharmaceutical drugs. The second presents best practices in developability assessments of early-stage biopharmaceutical drug candidates. In addition to raising awareness of the promise of computational research, this book also discusses solutions required to improve the success rate of translating biologic drug candidates into products available in the clinic. As such, it is a rich source of information on current principles and practices as well as a starting point for finding innovative applications of computation towards biopharmaceutical drug development.

Practical Aspects of Vaccine Development provides an academic and industry perspective on vaccine development and manufacturing. With the increasing complexity of vaccine products in development, there is a need for a comprehensive review of the current state of the industry and challenges being encountered. While formulation scientists working in biotherapeutic development may be familiar with proteins, vaccines present unique challenges. Vaccines include a wide range of components including proteins, polysaccharides, protein-polysaccharide conjugates, adjuvants, and more. The container closure system may also be unique, and the product may require freezing storage or lyophilization based on the stability of the vaccine components. Based on the route of delivery, novel technologies and devices may be required. Covering formulation development, manufacture, and delivery considerations of vaccine production, this book is essential to formulation scientists, researchers in vaccine development throughout medical and life sciences, and advanced students.

Focusing on nanoparticulate nanocarriers and recent advances in the field of drug delivery, the volume begins with chapters that provide an informative introduction to polymeric nanoparticles-their general physicochemical features and characteristics, their applications in drug delivery systems, and the challenges involved. Specific applications are discussed, with attention paid to treatment of particular diseases and disorders and the targeting of specific organs. Part 2 looks at more specific applications and techniques of nanoparticulate nanocarriers for drug delivery, such as the use of magnetic nanoparticles, gold nanoparticles in therapeutics, and superparamagnetic iron oxide nanoparticles (SPIONs) for the treatment of cancer. Part 3 discusses lipid-based nanoparticulates for various applications, including skin care. The last section of the book explores some of the newer nanoarchitectures, including dendrimers in gene delivery and carbon nanotubes for drug delivery. Together, the insightful research presented here provides valuable information for those involved in this area, including scientists and researchers and faculty and upper-level students, as well as for industry professionals.

Written for practitioners in both the drug and biotechnology industries, the Handbook of Analytical Validation carefully compiles current regulatory requirements on the validation of new or modified analytical methods. Shedding light on method validation from a practical standpoint, the handbook: Contains practical, up-to-date guidelines for analytical method validation Summarizes the latest regulatory requirements for all aspects of method validation, even those coming from the USP, but undergoing modifications Covers development, optimization, validation, and transfer of many different types of methods used in the regulatory environment Simplifying the overall process of method development, optimization and validation, the guidelines in the Handbook apply to both small molecules in the conventional pharmaceutical industry, as well as well as the biotech industry.

The objective of this book is to provide the fundamental comprehension of a broad range of topics in an integrated volume such that readership hailing from diverse disciplines can rapidly acquire the necessary background for applying it in pertinent research and development field.

While silk derived from silkworm has been of economic importance for centuries, more recently silkworm has been found to have utility in biomedicine. This has attracted attention for expressing eukaryotic recombinant proteins, which require post-translational modifications. In 1985 Dr. Susumu Maeda demonstrated that silkworm larvae could produce a functional human-interferon. Since then various techniques have been developed to express recombinant proteins in silkworm. With the development of the Bombyx mori nucleopolyhedrovirus (BmNPV) bacmid system, which is capable of replicating in both Escherichia coli and Bombyx mori derived cell lines or silkworm, silkworm larvae or pupae have been used for the expression system for recombinant protein production. This method has the advantage of a bacmid, in that it can be easily prepared for sufficient bacmid DNA for subsequent expression in silkworm. It is potentially a big breakthrough in production of recombinant eukaryotic proteins and viruses, which will be a powerful tool in a new proteome era. This volume contributes to the advancement of our knowledge in the subject, for example gene expression systems and silkworm research, and focuses on silkworm biofactories for the recombinant protein production and commercial applications of proteins.

Design and Analysis of Clinical Trials for Predictive Medicine provides statistical guidance on conducting clinical trials for predictive medicine. It covers statistical topics relevant to the main clinical research phases for developing molecular diagnostics and therapeutics-from identifying molecular biomarkers using DNA microarrays to confirming their clinical utility in randomized clinical trials. The foundation of modern clinical trials was laid many years before modern developments in biotechnology and genomics. Drug development in many diseases is now shifting to molecularly targeted treatment. Confronted with such a major break in the evolution toward personalized or predictive medicine, the methodologies for design and analysis of clinical trials is now evolving. This book is one of the first attempts to contribute to this evolution by laying a foundation for the use of appropriate statistical designs and methods in future clinical trials for predictive medicine. It is a useful resource for clinical biostatisticians, researchers focusing on predictive medicine, clinical investigators, translational scientists, and graduate biostatistics students.

Sets forth the history, state of the science, and future directions of drug discovery

Edited by Jie Jack Li and Nobel laureate E. J. Corey, two leading pioneers in drug discovery and medicinal chemistry, this book synthesizes great moments in history, the current state of the science, and future directions of drug discovery into one expertly written and organized work. Exploring all major therapeutic areas, the book introduces readers to all facets and phases of drug discovery, including target selection, biological testing, drug metabolism, and computer-assisted drug design.

"Drug Discovery" features chapters written by an international team of pharmaceutical and medicinal chemists. Contributions are based on a thorough review of the current literature as well as the authors' firsthand laboratory experience in drug discovery. The book begins with the history of drug discovery, describing groundbreaking moments in the field. Next, it covers such topics as: Target identification and validationDrug metabolism and pharmacokineticsCentral nervous system drugsIn vitro and in vivo assaysCardiovascular drugsCancer drugs

Each chapter features a case study, helping readers understand how science is put into practice throughout all phases of drug discovery. References at the end of each chapter serve as a gateway to groundbreaking original research studies and reviews in the field.

"Drug Discovery" is ideal for newcomers to medicinal chemistry and drug discovery, providing a comprehensive overview of the field. Veterans in the field will also benefit from the perspectives of leading international experts in all aspects of drug discovery.

Facilitates the discovery and development of new, effective therapeutics

With coverage of the latest mass spectrometry technology, this book explains how mass spectrometry can be used to enhance almost all phases of drug discovery and drug development, including new and emerging applications. The book's fifteen chapters have been written by leading pharmaceutical and analytical scientists. Their contributions are based on a thorough review of the current literature as well as their own experience developing new mass spectrometry techniques to improve the ability to discover and develop new and effective therapeutics.

"Mass Spectrometry for Drug Discovery and Drug Development" begins with an overview of the types of mass spectrometers that facilitate drug discovery and development. Next it covers: HPLC-high-resolution mass spectrometry for quantitative assaysMass spectrometry for siRNAQuantitative analysis of peptidesMass spectrometry analysis of biological drugsApplications that support medicinal chemistry investigationsMass spectrometry imaging and profiling

Throughout the book, detailed examples underscore the growing role of mass spectrometry throughout the drug discovery and development process. In addition, images of mass spectra are provided to explain how results are interpreted. Extensive references at the end of each chapter guide readers to the primary literature in the field.

"Mass Spectrometry for Drug Discovery and Drug Development" is recommended for readers in pharmaceutics, including medicinal chemists, analytical chemists, and drug metabolism scientists. All readers will discover how mass spectrometry can streamline and advance new drug discovery and development efforts.