Leading scientists offer detailed profiles of ten protein drugs currently in development. The case histories of these important new compounds are described from the perspective of their formulation, characterization, and stability. This ready reference also features recent data and an abundance of previously unpublished information. The in-depth coverage includes a highly useful compendium of degradation sites occurring in over 70 proteins. An invaluable aid in the rapid identification of potential hot spots' in proteins, this accessible compilation allows for inspection of the protein's primary structure and preparation of a hydroflex plot.

Although the potential for immunomodulation has been recognized for many years there has been an explosion of data in this field with relevance especially to the treatment of chronic airway diseases. Most of the work in this field has been conducted by Japanese investigators but in the last decade there has been a body of work outside of Japan that supports and enhances these findings. The book covers basic research like effects on bacteria, anti-inflammatory and mucoregulatory effects, but also clinical results with up-to-date information for the use of such medications to potentially treat diseases as diverse as chronic airway diseases, arthritis, inflammatory bowel disease, and cancer.
The volume is intended for pulmonary physicians, researchers in inflammation research, and pharmaceutical companies interested in the development of such agents. It provides background information for the clinician as well as in depth exploration of cutting edge science.

Gastric acid plays a primary role in digestion as well as in the sterilization of food and water. Gastric juice contains the most concentrated physiological acid solution (pH~1) as a result + - of H and Cl ion secretion [hydrochloric acid (HCl) production] by parietal cells in the oxyntic mucosa of the stomach. The combined output of the parietal cells leads to the sec- tion of 1-2 l of HCl at a concentration of 150-160 mmol/l into the interior of the stomach. In order to facilitate the production of acid, the parietal cell relies on the generation of a high + concentration of H ions that are transported into the lumen of the gland. This process is fa- + + cilitated by activation of the gastric H ,K -ATPase, which translocates to the apical pole of + - the parietal cell. K as well as ATP hydrolysis and Cl all play critical roles in the activation + + of gastric H ,K -ATPase and are essential for the functioning of the enzyme (Reenstra and Forte 1990). This review will examine the classical proteins that have been linked to acid secretion as well as some recently identi?ed proteins that may modulate gastric acid secretion, in - dition we discuss the known secretagogues, and their receptors including a new receptor, which upon stimulation can lead to acid secretion.

Biosimulation is an approach to biomedical research and the treatment of patients in which computer modeling goes hand in hand with experimental and clinical work. The models are used to interprete the experimental results and to accumulate information from experiment to experiment. The book explains the concepts used in the modeling of biological phenomena and goes on to present a series of well-documented models of the regulation of various genetic, cellular and physiological processes. We discuss how the use of computer models makes it possible to optimize the treatment of cancer for individual patients and explains how models of interacting nerve cells can be used to design new treatments for patients with Parkinson's disease. We discuss how use of models in industry will allow existing knowledge to be effectively applied, and the book ends with a presentation of the views of the regulatory agencies.

Furthering efforts to simulate the potency and specificity exhibited by peptides and proteins in healthy cells, this remarkable reference supplies pharmaceutical scientists with a wealth of techniques for tapping the enormous therapeutic potential of these molecules-providing a solid basis of knowledge for new drug design.
Provides a broad, comprehensive overview of peptides and proteins as mediators of cell movement, proliferation, differentiation, and communication.
Written by more than 50 leading international authorities, Peptides and Protein Drug Analysis
discusses strategies for dealing with the complexity of peptides and proteins in conformational flexibility and amino acid sequence variability
analyzes drug formulations facilitated by solid-phase peptide synthesis and recombinant DNA technology
examines chemical purity analysis by high-pressure chromatographic, capillary electrophoretic, gel electrophoretic, and isoelectric focusing methods
highlights drug design elements derived from protein folding, bioinformatics, and computational chemistry
demonstrates uses of unnatural mutagenesis and combinatorial chemistry
explores mass spectrometry, protein sequence, and carbohydrate analysis
illustrates bioassays and other new functional analysis methods
surveys spectroscopic techniques such as ultraviolet, fluorescence, Fourier transform infrared, and nuclear magnetic resonance (NMR)
addresses ways of distinguishing between levels of therapeutic and endogenous agents in cells
reviews structural analysis tools such as ultracentrifugation and light, X-ray, and neutron scattering
and more
Featuring over 3400 bibliographic citations and more than 500 tables, equations, and illustrations, Peptide and Protein Drug Analysis is a must-read resource for pharmacists; pharmacologists; analytical, organic, and pharmaceutical chemists; cell and molecular biologists; biochemists; and upper-level undergraduate and graduate students in these disciplines.

Our recent understanding of the cellular and molecular defects and the regulation of the apoptotic signalling pathways has resulted in rationally designed anticancer strategies and the development of novel agents that regulates apoptosis. A comprehensive review of all apoptotic-related anticancer therapies is not the purpose of this book. However, in the volume of this book with 11 chapters, we have described a number of novel apoptotic regulators that have shown promising value and also great feasibility for cancer treatment. These novel agents either occur naturally or are chemically synthesized. While we are excited about the discovery and development of these novel apoptotic regulators as potential anticancer agents, a degree of caution should be always borne in mind when interpreting the success of preclinical pro-apoptotic candidates since potential problems inevitably lie ahead. These problems usually include target specificity, unanticipated toxicity, compound stability, formulation issues, pharmacokinetic and pharmacodynamic profiles. Nevertheless, we believe that this collection of 11 chapters by established leaders in the area of apoptosis will be of great interest to not only academics working in the field of cancer research and apoptosis but also pharmaceutical and pharmacological industries that . We are looking forward to the further development to push these potential agents toward clinical stage.

Medicinal chemistry is both science and art. The science of medicinal chemistry offers mankind one of its best hopes for improving the quality of life. The art of medicinal chemistry continues to challenge its practitioners with the need for both intuition and experience to discover new drugs. Hence sharing the experience of drug research is uniquely beneficial to the field of medicinal chemistry. Drug research requires interdisciplinary team-work at the interface between chemistry, biology and medicine. Therefore, the topic-related series Topics in Medicinal Chemistry covers all relevant aspects of drug research, e.g. pathobiochemistry of diseases, identification and validation of (emerging) drug targets, structural biology, drugability of targets, drug design approaches, chemogenomics, synthetic chemistry including combinatorial methods, bioorganic chemistry, natural compounds, high-throughput screening, pharmacological in vitro and in vivo investigations, drug-receptor interactions on the molecular level, structure-activity relationships, drug absorption, distribution, metabolism, elimination, toxicology and pharmacogenomics. In general, special volumes are edited by well known guest editors.

Marking the 200th National Meeting of the American Chemical Society, The Division of Nuclear Chemistry and Technology hosted a group of about 90 scientists from 15 different countries to discuss the new trends in radiopharmaceutical synthesis, quality assurance and regulatory control. This event took place in Washington, D.C. on August 27-30, 1990. When I first suggested the idea for this symposium, a group of scientists who pioneered the proposed topics offered their help to organize and run such a big task with me. Their names are listed here in appreciation. Thomas E. Boothe Cyclotron Facility, Mt. Sinai Medical Center, Miami Beach, Florida, USA Robert F. Dannals Division of Nuclear Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA Anthony L. Feliu Julich Nuclear Research Center, Julich, Germany Joanna S. Fowler Chemistry Department, Brookhaven National Laboratory, Upton, New York, USA George W. Kabalka Department of Chemistry, University of Tennessee, Knoxville, Tennessee, USA Hank F. Kung Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA James F. Lamb Imagents, Inc., Houston, Texas, USA Harold A. O'Brien, Jr. Los Alamos National Laboratory, Los Alamos, New Mexico, USA Joseph R. Peterson Dept. of Chemistry, University of Tennessee, Knoxville, Tennessee, USA Hernan Vera Ruiz International Atomic Energy Agency, Vienna, Austria Roy S. Tilbury University of Texas, M. D. Anderson Cancer Center, Houston, Texas, USA In addition, a number of distinguished colleagues have participated in the process of reviewing the manuscripts presented in this volume. Their effort is sincerely acknowledged.

A compendium of proven experimental approaches and strategies for studying the bioactivation, detoxification, tissue distribution, and elimination of xenobiotics in the metabolism and/or transport of various chemicals. The authors address several of the major drug metabolizing systems, including the cytochrome P450 family, flavin-containing monooxygenases, glutathione, S-transferase, glucuronidation, N-acetylation, and sulfotransferases. Additional chapters present novel approaches to the study of: signaling pathways in the regulation of drug metabolism enzymes, how the modulation of thiols and other low molecular-weight cofactors can alter drug metabolism, and how modulation of drug metabolism pathways can influence antiviral therapy.

The need for effective therapy to treat Alzheimer 's disease is greater than ever, but there is still no drug therapy that can stop or reverse the progression of the disease. There is, however, a great deal of anticipation over the imminent development of effective therapies as a result of the identification of promising targets for drug development. This book investigates these targets and examines ongoing strategies to develop effective therapies for this devastating neurodegenerative condition.

This book presents the development and experimental validation of the structural test strategy called Oscillation-Based Test OBT in short. The results presented here assert, not only from a theoretical point of view, but also based on a wide experimental support, that OBT is an efficient defect-oriented test solution, complementing the existing functional test techniques for mixed-signal circuits.

Filled with strategies to minimize the adverse effects of injectable drugs, this book provides the scientific background and techniques required to evaluate parenteral formulations with respect to their potential to cause pain, irritation, and muscle damage. Using a unique, interdisciplinary approach, the book's editors and contributors represent the areas of pharmaceutics, physiology, anatomy, toxicology, and product formulation. The chapters cover topics such as muscle damage with injectables, in vitro and in vivo cystolic enzyme release, histological and morphological methods, assessing pain, cosolvents in injectables, biodegradable microparticles, and more.

Following reviews on sleep physiology, regulation, pharmacology, and the neuronal networks regulating sleep and awakening, as well as a classification of sleep disorders, this book presents a number of major breakthroughs in the treatment of those disorders. These include recently approved drugs for treating insomnia, such as Doxepin; variations on previously approved molecules, e.g. Zolpidem sublingual preparation; or new chemical entities in advanced stages of clinical development, e.g. Orexin antagonists. Further topics discussed include drugs acting on the GABA receptor, such as Lorediplon and Eszopiclone; the treatment of excessive daytime drowsiness with cell therapy and drugs such as Modafinil, Armodafinil and Sodium oxybate; and the use of Tasimelteon in the treatment of circadian sleep disorders.

Granulocyte colony-stimulating factor (G-CSF or GCSF) is a secreted glycoprotein that stimulates the proliferation and differentiation of granulocyte precursor cells, and induces mobilization of peripheral blood progenitor cells from the bone marrow. Development of recombinant human G-CSF has had a profound impact on the treatment of many diseases, including severe chronic neutropenia and cancer, and has enabled peripheral stem cell transplantation to supplant bone marrow transplantation in the autologous setting. This Milestones in Drug Therapy volume describes the experience of the last 20 years of treatment with recombinant human G-CSF, including the basic science, the use of recombinant human G-CSF in both the oncology and nononcology settings, and the safety and economics of its use. Many of the authors were the original investigators of recombinant human G-CSF and other authors are key researchers who provide their outlook for the next 20 years for use of and research with recombinant human G-CSF.

Medicinal chemistry is both science and art. The science of medicinal chemistry offers mankind one of its best hopes for improving the quality of life. The art of medicinal chemistry continues to challenge its practitioners with the need for both intuition and experience to discover new drugs. Hence sharing the experience of drug research is uniquely beneficial to the field of medicinal chemistry. Drug research requires interdisciplinary team-work at the interface between chemistry, biology and medicine. Therefore, the topic-related series Topics in Medicinal Chemistry covers all relevant aspects of drug research, e.g. pathobiochemistry of diseases, identification and validation of (emerging) drug targets, structural biology, drugability of targets, drug design approaches, chemogenomics, synthetic chemistry including combinatorial methods, bioorganic chemistry, natural compounds, high-throughput screening, pharmacological in vitro and in vivo investigations, drug-receptor interactions on the molecular level, structure-activity relationships, drug absorption, distribution, metabolism, elimination, toxicology and pharmacogenomics. In general, special volumes are edited by well known guest editors.

This book covers wide areas of animal and human psychopharmacology with clinical utility in the treatment of psychiatric and neurological (e.g Alzheimer's disease) disorders. The main theme is to develop a new paradigm for drug discovery that questions the claim that animal models or assays fail adequately to predict Phase 3 clinical trials. A new paradigm is advocated that stresses the importance of intermediate staging points between these extremes that depend on suitable translation of findings from animal studies to Phase 1 or Phase 2 studies utilising experimental medicine.

Records cataloging the healing powers of natural substances - plants, minerals, and animal byproducts - date back more than 4,000 years. There is no denying the effectiveness of traditional Chinese medicine, yet - until recently - the roots of this knowledge were largely lost in superstition and folklore. However, the use of herbs as an alternative medical treatment for many illnesses has increased steadily over the last decade, particularly since such herbs are categorized as "Natural Food Products" and are not yet subject to strict control by the FDA. Reports published in 1996 indicate that more than 10% of the US population has used herbal remedies.

This book does not debate the value of Eastern or Western medicine but brings together Chinese herbal lore and Western scientific methods in a current, comprehensive treatise on the pharmacology of Chinese herbs. This second edition of The Pharmacology of Chinese Herbs presents the chemical composition, pharmacological action, toxicity, and therapeutic value of 473 herbs.

The book:
o Classifies herbs according to their therapeutic value
o Informs how active ingredients in herbs may adversely interact with other herbs or drugs
o Evaluates which herbs have the potential for more investigation and possible use as drugs
o Describes the pharmacological action of each herb based on recent scientific study and describes each herb according to Chinese pharmacopoeia and folk medicine
o Provides a review of Chinese medical history
o Presents information on how to use modern chemical techniques for enhancing or modifying herbal ingredients into better agents with more strength and activity


What's New in the Second Edition
Discussions on:
o Herbs and their specific effects on the immune system
o Herbs and fertility/infertility
o Anti-cancer herbs
o Anti-HIV herbs
o Anti-malarial herbs
o Ginseng and ginsenosides
o Anti-Alzheimer herbs
o Herbs affecting the nervous system

Nikolaus Seiler, Benoit Duranton and Francis Raul: The polyamine oxidase inactivator MDL 72527.- Zhi Hong and Craig E. Cameron: Pleiotropic mechanisms of ribavirin antiviral activities.- Jie Hong Hu and Charles Krieger: Protein phosphorylation networks in motor neuron death.- James O. Schenk: The functioning neuronal transporter for dopamine: kinetic mechanisms and effects of amphetamines, cocaine and methylphenidate.- Laszlo Prokai: Central nervous system effects of thyrotropin-releasing hormone and ist analogues: opportunities and perspectives for drug discovery and development.- David F. Horrobin: A new category of psychotropic drugs: neuroactive lipids as exemplified by ethyl eicosapentaenoate (E-E).- Suprabhat Ray, Reema Rastogi and Atul Kumar: Current status of estrogen receptors

In this fast moving field the main goal of this volume is to provide up-to-date information on the molecular and functional properties and pharmacology of mammalian TRP channels. Leading experts in the field will describe properties of a single TRP protein/channel or portray more general principles of TRP function and important pathological situations linked to mutations of TRP genes or their altered expression. Thereby this volume on Transient Receptor Potential (TRP) Channels provides valuable information for readers with different expectations and backgrounds, for those who are approaching this field of research as well as for those wanting to make a trip to TRPs.

This book can be used to provide insight into this important application of biophysics for those who are planning a career in protein therapeutic development, and for those outside this area who are interested in understanding it better. The initial chapters describe the underlying theory, and strengths and weaknesses of the different techniques commonly used during therapeutic development. The majority of the chapters discuss the applications of these techniques, including case studies, across the product lifecycle from early discovery, where the focus is on identifying targets, and screening for potential drug product candidates, through expression and purification, large scale production, formulation development, lot-to-lot comparability studies, and commercial support including investigations.

Metered Dose Inhaler Technology explores the technologies of pressurized metered dose inhalation (MDI) delivery systems and provides practical, easy-to-use guidance to effective product formulation. With contributions from an international panel of authors, the book addresses the global phase-out of chloroflurocarbon chemicals (CFCs), the generation of propellant systems to replace them, and their associated new medications and therapies. Topics include the manufacture of metered dose inhalers, particle size analysis in inhalation therapy, development and testing, pharmcokinetics and metabolism of propellants, toxicology, and more.