The inspiration for this text was the 1988 volume by Alder and Zbinden, written before the ICH harmonization process for drug safety evaluation (or its ISO analog for device biocompatibility evaluation) had been initiated or come to force. Since then, much has changed in both the world and practice of medicine and the regulation of drugs. The intent of this volume is to provide similar guidance as to what nonclinical safety assessment tests need to be performed to move a drug into man, through development and to market approved (this intent was subsequently extended to cover the closely related medical device biotechnology, and combination product fields) in a concise, abbreviated manner for all the major world market countries.

In the literature, several terms are used synonymously to name the topic of this book: chem-, chemi-, or chemo-informatics. A widely recognized de- nition of this discipline is the one by Frank Brown from 1998 (1) who defined chemoinformatics as the combination of "all the information resources that a scientist needs to optimize the properties of a ligand to become a drug. " In Brown's definition, two aspects play a fundamentally important role: de- sion support by computational means and drug discovery, which distinguishes it from the term "chemical informatics" that was introduced at least ten years earlier and described as the application of information technology to ch- istry (not with a specific focus on drug discovery). In addition, there is of course "chemometrics," which is generally understood as the application of statistical methods to chemical data and the derivation of relevant statistical models and descriptors (2). The pharmaceutical focus of many developments and efforts in this area-and the current popularity of gene-to-drug or si- lar paradigms-is further reflected by the recent introduction of such terms as "discovery informatics" (3), which takes into account that gaining kno- edge from chemical data alone is not sufficient to be ultimately successful in drug discovery. Such insights are well in accord with other views that the boundaries between bio- and chemoinformatics are fluid and that these d- ciplines should be closely combined or merged to significantly impact b- technology or pharmaceutical research (4).

Attention has recently turned to using plants as hosts for the production of commercially important proteins. The twelve case studies in this volume present successful strategies for using plants to produce industrial and pharmaceutical proteins and vaccine antigens. They examine in detail projects that have commercial potential or products that have already been commercialized, illustrating the advantages that plants offer over bacterial, fungal or animal cell-culture hosts. There are many indications that plant protein production marks the beginning of a new paradigm for the commercial production of proteins that, over the next decade, will expand dramatically.

Founded in 1959 by its current Editor, the series has moved from its initial focus on medicinal chemistry to a much wider scope. Today it encompasses all fields concerned with the development of new therapeutic drugs and the elucidation of their mechanisms of action, reflecting the increasingly complex nature of modern drug research. Invited authors present their biological, chemical, biochemical, physiological, immunological, pharmaceutical, toxicological, pharmacological and clinical expertise in carefully written reviews and provide the newcomer and the specialist alike with an up-to-date comprehensive list of prime references. Each volume of Progress in Drug Research contains fully cross-referencing indices which link the books together, forming a virtually encyclopaedic work. The series thus serves as an important, time-saving source of information for researchers concerned with drug research and all those who need to keep abreast of the many recent developments in the quest for new and better medicines.

Long acting veterinary formulations play a significant role in animal health, production and reproduction within the animal health industry. Such technologies offer beneficial advantages to the veterinarian, farmer and pet owner. These advantages have resulted in them growing in popularity in recent years.

The pharmaceutical scientist is faced with many challenges when innovating new products in this demanding field of controlled release. This book provides the reader with a comprehensive guide on the theories, applications, and challenges associated with the design and development of long acting veterinary formulations. The authoritative chapters of the book are written by some of the leading experts in the field. The book covers a wide scope of areas including the market influences, preformulation, biopharmaceutics, in vitro drug release testing and specification setting to name but a few. It also provides a detailed overview of the major technological advances made in this area. As a result this book covers everything a formulation scientist in industry or academia, or a student needs to know about this unique drug delivery field to advance health, production and reproduction treatment options and benefits for animals worldwide."

This book describes 200 bio-polymers, including the most recent and advanced nanotechnology applications. The applications of various bio-medical and other future potential uses are covered and examined in depth. Systematic discussion of current leading natural polymers is also included.

The concept of focal controlled drug delivery has been applied for treating illnesses that are localized to a certain tissue or organ. These delivery systems are applied directly to the diseased site and deliver a desired dose for an extended time period while minimizing systemic distribution of toxic drug. Controlled drug delivery systems have been focused on oral extended release formulations and on systemic delivery of small drugs and peptides. Despite the upsurge of interest in focal targeted drug delivery, there is currently no single reference text on the subject. By comparison, there are numerous authored and edited books on oral, systemic and transdermal drug delivery or books on biodegradable polymers as drug carriers. Thus, the aim of Focal Drug Delivery is to bring together leading experts and researchers in the field to provide an authoritative account of the essential pharmaceutical, technological, physiological and biological sciences underpinning the topic. In addition, the book will review advances in treatment options for diseases localized at a certain tissue or organ.

Introduction to Fragment-Based Drug Discovery, by Daniel A. Erlanson

Fragment Screening Using X-Ray Crystallography, by Thomas G. Davies and Ian J. Tickle

Hsp90 Inhibitors and Drugs from Fragment and Virtual Screening, by Stephen Roughley, Lisa Wright, Paul Brough, Andrew Massey and Roderick E. Hubbard

Combining NMR and X-ray Crystallography in Fragment-Based Drug Discovery: Discovery of Highly Potent and Selective BACE-1 Inhibitors, by Daniel F. Wyss, Yu-Sen Wang, Hugh L. Eaton, Corey Strickland, Johannes H. Voigt, Zhaoning Zhu and Andrew W. Stamford

Combining Biophysical Screening and X-Ray Crystallography for Fragment-Based Drug Discovery, by Michael Hennig, Armin Ruf and Walter Huber

Targeting Protein Protein Interactions and Fragment-Based Drug Discovery, by Eugene Valkov, Tim Sharpe, May Marsh, Sandra Greive and Marko Hyvonen

Fragment Screening and HIV Therapeutics, by Joseph D. Bauman, Disha Patel and Eddy Arnold

Fragment-Based Approaches and Computer-Aided Drug Discovery, by Didier Rognan"

This monograph is devoted to different aspects associated with citric acid, inorganic citrates and their aqueous and organic solutions. It includes information about properties, occurrence and technological applications of citric acid and inorganic citrates. Phase equilibria - melting, freezing, boiling, vapour pressures, solubilities of citric acid in water, organic solvents and ternary systems are presented, correlated, and analyzed. Dynamic properties - viscosities, diffusion coefficients, electrical conductivities and surface tensions are examined. Mathematical representations of citric acid dissociation, in electrolyte solutions and in buffers are discussed. Citric acid chemistry - syntheses of citric acid, neutralization, degradation, oxidation, esterification, formation of anhydrides, amides and citrate-based siderophores is reviewed.

Over the past twelve years, the Centre for Medicines Research has held a series of Workshops on a number of topics related to the drug discovery and development process. The major objective of these Workshops has been to provide an international forum for regula tory, academic and industry representatives to debate together, and suggest solutions to, specific problems. The meeting reported in this volume represents a departure from this approach, in that the par ticipants were drawn largely from the pharmaceutical industry. Senior clinicians, pharmacologists and toxicologists from companies in Europe, the USA and Japan met in May 1994 to discuss a scientific rationale for the conduct of toxicity studies to support the clinical development of new medicines, and to begin to work towards an industry consensus. Achievement of such a consensus is seen as an important step in the process leading towards international harmon isation of the recommendations on the timing of toxicity studies in relation to clinical trials."

The aim of this volume is to review the state-of-the-art in analytical voltammetry with regard to theory and instrumentation, and show how these relate to the analysis of inorganic, organometallic, organic and biological molecules. Modern voltammetric techniques have practical applications in biological, pharmaceutical and environmental chemistry. The growing importance of voltammetry in the development of modified electrodes and biological electrodes and chemical and biological sensors is also highlighted.

Penicillins and cephalosporins have a long history in combating bacterial infections. Despite new infectious diseases and occurring resistance, beta-lactam antibiotics will for many years to come continue to play a prominent role in our therapeutic arsenal. This book covers the industrial development of the chemical and biochemical processes used to manufacture these products, as well as looking ahead to possible future processes. The interplay between synthetic organic chemistry with the understanding and application of enzymes, modeling of fermentation processes and integration through (bio-) chemical process engineering is illustrated. In-depth scientific approaches to biocatalysis and biocatalyst development including enzyme kinetics, enzyme crystal studies and semi-rational enzyme mutations are also presented. Metabolic pathway analysis and modeling of fermentation process are treated as well as molecular precision in synthetic approaches to beta-lactams, their precursors and derivatives. Process technology studies including new reactor concepts, possible short-cut routes and improved down-stream-processing methods complete a broad view on the scope and limitations of the presently developed industrial processes including an intriguing insight into future process possibilities. This book represents an excellent case study on the transformation of traditional, stoAchiometric, organic synthesis and classical fermentations into modern (bio-) catalysis and biosynthesis based on insights in metabolic pathways and enzyme actions.

This book details current developments in all natural polymers, with a focus on animal and microbial polysaccharides. The book examines, compares, and contrasts the efficiency of plant and algae based natural polymers in inducing immune reactions. Additionally, the book details the safety and toxicity profiles with respective regulations.

Over the past years, the chem(o)informatics field has further evolved and new application areas have opened up, for example, in the broadly defined area of chemical biology. In Chemoinformatics and Computational Chemical Biology, leading investigators bring together a detailed series of reviews and methods including, among others, system-directed approaches using small molecules, the design of target-focused compound libraries, the study of molecular selectivity, and the systematic analysis of target-ligand interactions. Furthermore, the book delves into similarity methods, machine learning, probabilistic approaches, fragment-based methods, as well as topics that go beyond the current chemoinformatics spectrum, such as knowledge-based modeling of G protein-coupled receptor structures and computational design of siRNA libraries. As a volume in the highly successful Methods in Molecular Biology (TM) series, this collection provides detailed descriptions and implementation advice that are exceedingly relevant for basic researchers and practitioners in this highly interdisciplinary research and development area. Cutting-edge and unambiguous, Chemoinformatics and Computational Chemical Biology serves as an ideal guide for experts and newcomers alike to this vital and dynamic field of study.

This thesis mainly describes the development of a screening process for a mirror-image library of chiral natural products. It demonstrates how, by using mirror-image proteins for the screening of available natural products, unavailable mirror-image isomers of natural products can be screened in a mirror process. Moreover, as mirror-image isomers including target proteins and natural products are mainly prepared by means of chemical synthesis, the screening strategy presented here suggests the importance of organic chemistry. Natural products are commonly used as valuable resources for drug discovery. However, as they are mostly produced as single enantiomeric forms, researchers have tested o nly natural products bearing one stereochemistry available in nature. As natural products and their enantiomers have identical physicochemical properties and different biological activities, mirror-image isomers of natural products are promising candidates for novel medicinal resources. In an effort to identify anticancer agents from the mirror-image library, chemical protein syntheses of some target oncoproteins, MDM2, MDMX and Grb2, and their applications to the chemical array screening process were achieved. In the course of this process the NP843 enantiomer, which is the enantiomer of an -tocopherol derivative, was successfully identified as a novel MDM2-p53 interaction inhibitor. These results clearly show that a mirror-image library of chiral natural products represents an invaluable medicinal resource. Accordingly, the chemistry-based screening strategy described in this thesis will be of great interest to a broad range of chemists involved in natural product, medicinal, and synthetic chemistry.

Bioinformatics and Drug Discovery describes the bioinformatic approaches and techniques employed along the pipeline of drug development from genes to proteins to drugs. The book focuses on gene microarray analysis and techniques for target identification and validation. In addition, clinical applications showing how the analysis can be used for prognostication and diagnosis are described. The second section focuses on protein analysis, including target validation and identification using modern proteomic analysis as well as protein modeling techniques. The third section discusses chemoinformatics, including virtual screening and how to computationally approach chemical space.

Fullerene Collision Reactions provides a comprehensive overview of the state-of-the-art of fullerene collision studies. The book begins with introductory chapters that provide the necessary background in experimental and theoretical techniques. This is followed by experimental results and theoretical calculations covering the wide range of available gas-phase fullerene collision experiments.
Emphasis is placed on gas-phase molecular beam experiments where reaction, fragmentation and charge transfer cross sections have been determined covering collision energy ranges from thermal to MeV. Atomic, ionic, electronic, cluster and surface collisions involving fullerenes are covered in depth accompanied by a clear presentation of the most commonly applied experimental and theoretical techniques.
This book will be an invaluable resource for senior undergraduate students, graduate students and researchers working in the field.

This volume provides readers with the basic principles and fundamentals of extrusion technology and a detailed description of the practical applications of a variety of extrusion processes, including various pharma grade extruders. In addition, the downstream production of films, pellets and tablets, for example, for oral and other delivery routes, are presented and discussed utilizing melt extrusion. This book is the first of its kind that discusses extensively the well-developed science of extrusion technology as applied to pharmaceutical drug product development and manufacturing. By covering a wide range of relevant topics, the text brings together all technical information necessary to develop and market pharmaceutical dosage forms that meet current quality and regulatory requirements. As extrusion technology continues to be refined further, usage of extruder systems and the array of applications will continue to expand, but the core technologies will remain the same.

"Nanotechnology in Dermatology" is the first book of its kind to address all of the important and rapidly growing aspects of nanotechnology as it relates to dermatology. In the last few years there has been an explosion in research and development for products and devices related to nanotechnology, including numerous applications for consumers, physicians, patients, and industry. Applications are underway in medicine and dermatology for the early detection, diagnosis, and targeted therapy of disease, and nanodesigned materials and devices are expected to be faster, smaller, more powerful, more efficient, and more versatile than their traditional counterparts.

Written by experts working in this exciting field, "Nanotechnology in Dermatology" specifically addresses nanotechnology in consumer skin care products, in the diagnosis of skin disease, in the treatment of skin disease, and the overall safety of nanotechnology. The book also discusses future trends of this ever-growing and changing field, providing dermatologists, pharmaceutical companies, and consumer cosmetics companies with a clear understanding of the advantages and challenges of nanotechnology today."

A particular issue for biopharmaceuticals that has not been addressed comprehensively in any book, is the potential of an immune response to the biopharmaceutical product. That is, the human body marks the drug as a foreign body, and develops antibodies against the drug. These antibodies may be relatively harmless, but may also cross-react with the endogenous compound, causing autoimmunogenicity. Recent adverse experiences in Europe with Janssen-Ortho's blockbuster product Eprex has increased the attention towards potential immunogenicity of biopharmaceuticals, above all from the regulatory agencies. This book is intended to give a broad overview of the current state-of-the-art regarding the immune response to biopharmaceuticals. The chapters range from an overview of the immune system and factors that may trigger the immune system, via detection of antibodies and clinical implications, to various case examples and the regulatory view on immunogenicity.

After 13 years there are new areas to discuss and more recent trials to be included. Good clinical practice; evaluation of quality of life; measurement of the benefit: risk comparison; determination of cost- effectiveness and cost utility; stopping rules for trials; meta-analysis and subgroup analysis are all new sections. The references are expanded from 305 to 512 and include the recent advances in trial design, such as the n-of-1 trials and megatrials, and up-to-date examples to illustrate the points made in the 20 chapters.

Drug research and discovery are of critical importance in human health care. Computational approaches for drug lead discovery and optimization have proven successful in many recent research programs. These methods have grown in their effectiveness not only because of improved understanding of the basic science - the biological events and molecular interactions that define a target for therapeutic intervention - but also because of advances in algorithms, representations, and mathematical procedures for studying such processes. This volume surveys some of those advances. A broad landscape of high-profile topics in computer-assisted molecular design (CAMD) directed to drug design are included. Subject areas represented in the volume include receptor-based applications such as binding energy approximations, molecular docking, and de novo design; non-receptor-based applications such as molecular similarity; molecular dynamics simulations; solvation and partitioning of a solute between aqueous and nonpolar media; graph theory; non-linear multidimensional optimization, processing of information obtained from simulation studies, global optimization and search strategies, and performance enhancement through parallel computing.

Transporters in Drug Development examines how membrane transporters can be dealt with in academic-industrial drug discovery and pharmaceutical development as well as from a regulatory perspective. The book describes methods and examples of in vitro characterization of single transporters in the intestines, liver and kidneys as well as characterization of substrate overlap between various transporters. Furthermore, probes and biomarkers are suggested for studies of the transporters' impact on the pharmacokinetics of drug substrates/candidates interacting on transporters. The challenges of translating in vitro observed interaction of transporters into in vivo relevance are explored, and the book highlights perspectives of applying targeted proteomics and mechanistic modeling in this process.

This book is devoted to the graphics of patient data: good graphs enabling straight-forward and intuitive interpretation, efficient creation, and straightforward interpretation. We focus on easy access to graphics of patient data: the intention is to show a large variety of graphs for different phases of drug development, together with a description of what the graph shows, what type of data it uses, and what options there are. The main aim is to provide inspiration in form of a graphics cookbook. Many graphs provide creative ideas about what can be done. The book is not intended to be technical. It introduces general principles of good visualization to make readers understand the concepts, but the main focus is on the creativity and usefulness: readers are enabled to browse through the book to get ideas of how their own data can be analyzed graphically.

For additional information visit Editor s companion website: http: //www.elmo.ch/doc/life-science-graphics/