Cutting-edge investigators review the current status of the entire field, from the biology of MMPs through the current clinical studies. The authors include many leading scientists from pharmaceutical companies who present all the latest concepts and results on the preferred design strategies for MMP inhibitors, their molecular mechanisms, and their substrates. In addition, they fully describe their personal research on specific MMP inhibitors, detailing vanguard design strategies, their in vitro activity, the outcome of animal model studies and, where available, their toxicology, safety, efficacy in human clinical trials. Comprehensive and state-of-the-art, Matrix Metalloproteinase Inhibitors in Cancer Therapy offers basic and clinical investigators alike a richly informative summary of all the latest research on these powerful new drugs, and their high promise as emerging cancer therapeutics.

The association of matrix metalloproteinases (MMPs)-enzymes that disrupt the body's normal repair functions-with several diseases, including growing and invasive tumors, holds the tantalizing promise that their inhibiton might have therapeutic value. In Matrix Metalloproteinase Inhibitors in Cancer Therapy, cutting-edge investigators review the current status of the entire field, from the biology of MMPs through the current clinical studies. The authors include many leading scientists from pharmaceutical companies who present all the latest concepts and results on the preferred design strategies for MMP inhibitors, their molecular mechanisms, and their substrates. In addition, they fully describe their company's research effort on specific MMP inhibitors, detailing vanguard design strategies, their in vitro activity, the outcome of animal model studies and, where available, their toxicology, safety, and efficacy in human clinical trials. Comprehensive and state-of-the-art, Matrix Metalloproteinase Inhibitors offers basic and clinical investigators alike a richly informative summary of all the latest research on these powerful new drugs, and their high promise as emerging cancer therapeutics.

Cell Surface Proteases provides a comprehensive overview of these important enzymes that catalyze the hydrolysis of a protein as it degrades to a simpler substance. In the 1990s, an explosion of new discoveries shed light on the role of cell surface proteases and extended it beyond degradation of extracellular matrix components to include its influence on growth factors, cell signaling, and other cellular events. This volume unites the scientific literature from across disciplines and teases out unified themes of interactions between cell surface proteases and interconnecting cell surface-related systems -- including integrins and other adhesion molecules. Scientists and students involved in developmental biology, cell biology and disease processes will find this an indispensable resource.* Provides an overview of the entire field of cell surface proteases in a single volume* Presents major issues and astonishing discoveries at the forefront of modern developmental biology and developmental medicine * A thematic volume in the longest-running forum for contemporary issues in developmental biology with over 30 years of coverage

Here in a single source is a complete spectrum of ideas on the development of new anticancer drugs. Containing concise reviews of multidisciplinary fields of research, this book offers a wealth of ideas on current and future molecular targets for drug design, including signal transduction, the cell division cycle, and programmed cell death. Detailed descriptions of sources for new drugs and methods for testing and clinical trial design are also provided. - One work that can be consulted for all aspects of anticancer drug development - Concise reviews of research fields, combined with practical scientific detail, written by internationally respected experts - A wealth of ideas on current and future molecular targets for drug design, including signal transduction, the cell division cycle, and programmed cell death - Detailed descriptions of the sources of new anticancer drugs, including combinatorial chemistry, phage display, and natural products - Discussion of how new drugs can be tested in preclinical systems, including the latest technology of robotic assay systems, cell culture, and experimental animal techniques - Hundreds of references that allow the reader to access relevant scientific and medical literature - Clear illustrations, some in color, that provide both understanding of the field and material for teaching

Medicinal Chemistry of Anticancer Drugs, Second Edition, provides an updated treatment from the point of view of medicinal chemistry and drug design, focusing on the mechanism of action of antitumor drugs from the molecular level, and on the relationship between chemical structure and chemical and biochemical reactivity of antitumor agents. Antitumor chemotherapy is a very active field of research, and a huge amount of information on the topic is generated every year. Cytotoxic chemotherapy is gradually being supplemented by a new generation of drugs that recognize specific targets on the surface or inside cancer cells, and resistance to antitumor drugs continues to be investigated. While these therapies are in their infancy, they hold promise of more effective therapies with fewer side effects. Although many books are available that deal with clinical aspects of cancer chemotherapy, this book provides a sorely needed update from the point of view of medicinal chemistry and drug design. - Presents information in a clear and concise way using a large number of figures - Historical background provides insights on how the process of drug discovery in the anticancer field has evolved - Extensive references to primary literature

The tetracyclines have an illustrious history as therapeutic agents which dates back over half a century. Initially discovered as an antibiotic in 1947, the four ringed molecule has captured the fancy of chemists and biologists over the ensuing decades. Of further interest, as described in the chapter by George Armelagos, tetracyclines were already part of earlier cultures, 1500-1700 years ago, as revealed in traces of drug found in Sudanese Nubian mummies. The diversity of chapters which this book presents to the reader should illus trate the many disciplines which have examined and seen benefits from these fascinating natural molecules. From antibacterial to anti-inflammatory to anti autoimmunity to gene regulation, tetracyclines have been modified and redesigned for various novel properties. Some have called this molecule a biol ogist's dream because of its versatility, but others have seen it as a chemist's nightmare because of the synthetic chemistry challenges and "chameleon-like" properties (see the chapter by S. Schneider).

Of the thousands of novel compounds that a drug discovery project team invents and that bind to the therapeutic target, typically only a fraction of these have sufficient ADME/Tox properties to become a drug product. Understanding ADME/Tox is critical for all drug researchers, owing to its increasing importance in advancing high quality candidates to clinical studies and the processes of drug discovery. If the properties are weak, the candidate will have a high risk of failure or be less desirable as a drug product. This book is a tool and resource for scientists engaged in, or preparing for, the selection and optimization process. The authors describe how properties affect in vivo pharmacological activity and impact in vitro assays. Individual drug-like properties are discussed from a practical point of view, such as solubility, permeability and metabolic stability, with regard to fundamental understanding, applications of property data in drug discovery and examples of structural modifications that have achieved improved property performance. The authors also review various methods for the screening (high throughput), diagnosis (medium throughput) and in-depth (low throughput) analysis of drug properties. - Serves as an essential working handbook aimed at scientists and students in medicinal chemistry - Provides practical, step-by-step guidance on property fundamentals, effects, structure-property relationships, and structure modification strategies - Discusses improvements in pharmacokinetics from a practical chemist's standpoint

Matrix Metalloproteinases and Tissue Remodeling in Health and Disease: Target Tissues and Therapy, Volume, Volume 148, the latest volume in the Progress in Molecular Biology and Translational Science series covers a variety of timely topics, with chapters focusing on The Role of Matrix Metalloproteinases in Development, Repair, and Destruction of the Lungs, Matrix Metalloproteinases in Kidney Disease: Role in Pathogenesis and Potential as a Therapeutic Target, Regulation of Matrix Metalloproteinase in the Pathogenesis of Diabetic Retinopathy, Matrix Metalloproteinases in Normal Pregnancy and Preeclampsia, and Matrix Metalloproteinases, Neural Extracellular Matrix, and Central Nervous System Pathology. This volume is the second part of a thematic on matrix metalloproteinases and tissue remodeling in health and disease. It focuses on the role of MMPs in other systems, target tissues, and pathological disorders and the potential benefits of MMP inhibitors in various disorders. Serves as the second part of a thematic on matrix metalloproteinases and tissue remodeling in health and disease Focuses on cardiovascular remodeling Contains contributions from leading authorities on the topics Publishes cutting-edge reviews in molecular biology

Prostate cancer is the most common noncutaneous prostate cancer. Research has revealed several distinct malignancy and the second leading cause of cancer mechanisms of castration-resistant disease that may deaths among men in the United States. It is a critical converge in patients with disease progression on public health problem and remains incurable in the ADT. Many approaches are currently being evaluated metastatic setting with mortality that usually occurs as to improve the treatment of this condition and these a result of castration-resistant disease. fndings have identifed several potential targets for Since Huggins and Hodges’ report of the dra- therapeutic intervention. These include drugs that are matic clinical effects of suppressing serum testos- more active or less toxic chemotherapy agents; drugs terone levels in men with advanced prostate cancer that induce androgen deprivation; drugs that target in 1941, hormone therapy (also called androgen the androgen receptor and/or androgen synthesis; deprivation therapy [ADT]) has become widely drugs that target specifc pathways, including ang- accepted as the mainstay of therapy for the treat- genesis and tyrosine kinase inhibitors, endothelin ment of advanced prostate cancer. ADT combined antagonists and matrix metalloproteinase inhibitors; with radiation therapy is a standard of care in the and immunologic approaches. Many of these agents treatment of men with locally advanced prostate seem promising and the rationale and effcacy of cancer on the basis of evidence that shows improved these emerging therapies remain to be validated in survival. The role of ADT in the management of future clinical trials.

Treatment of patients with a brain tumor remains one of the most challenging and difficult areas of modern oncology. Recent advances in the molecular biology of these neoplasms have improved our understanding of the malignant phenotype and have lead to the development of novel forms of chemotherapy, including "targeted agents. The Handbook of Brain Tumor Chemotherapy reviews the state-of-the-art of chemotherapy development and clinical treatment of patients with this devastating disease. Handbook of Brain Tumor Chemotherapy offers a unique cutting-edge compendium of basic science and clinical information on the subject of brain tumor chemotherapy, reviewing what has been accomplished thus far and how the field will continue to evolve with the development of more specific and efficacious chemotherapeutic agents. This book represents the most complete single-volume resource available for information on the subject of brain tumor chemotherapy. - Provides the most up to date information regarding conventional forms of cytotoxic chemotherapy, as well as the basic science and clinical application of molecular therapeutics, for the treatment of brain tumors - Broadly appeals to anyone interested in the field of Neuro-Oncology and in the treatment of patients with brain tumors - Useful to clinicians interested in a thorough overview of the use of chemotherapy in patients with a broad range of brain tumors as well as serving as a source of background information to basic scientists and pharmaceutical researchers with an interest in the molecular therapeutics of brain tumors