Chemokine Receptors As Drug Targets

Chemokines are hormone-like signaling molecules secreted by cells to signal infection and guide the immune response. Following a decade of basic chemokine research, the pharmaceutical industry has now begun to exploit this crucial signaling pathway for the development of innovative drugs against AIDS, cancer, neural and autoimmune diseases. Here is the first reference focusing on these novel drug development opportunities. Opening with a general introduction on chemokine function and chemokine receptor biology, the second part covers the known implications of these signaling molecules in human diseases, such as cancer, neural disorders, and viral infection, including AIDS. The third part systematically surveys current drug development efforts at targeting individual chemokine receptors, as well as other chemokine interaction partners, including up-to-date reports from the pharmaceutical industry.

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.

Chemokines are a superfamily of low molecular weight cytokines that were initially described based on their ability to induce the directed migration of leukocytes to sites of inflammation or injury. In humans, there are approximately 45 chemokines that bind to 19 G-protein-coupled receptors. In addition to mediating cellular migration, chemokines have now been shown to affect many cellular functions including survival, adhesion, invasion, proliferation, and to regulate circulating chemokine levels. Although chemokine receptors were first described on leukocytes, it is now appreciated that chemokine receptors are also expressed by many other cells including endothelial and epithelial cells. Since the first description of chemokine receptors on malignant cells in 2001, an extensive literature has developed describing the expression and function of chemokine receptors in many malignancies. These studies support the initial hypothesis that malignant cells use chemokine receptors to migrate to distant sites of ligand expression and that expression of certain receptors is associated with a poor prognosis. It has also become apparent that malignancies of different tissues may use a diverse profile of chemokine receptors and that the same receptor may mediate metastasis to different sites in tumors of different histological origins. Receptor function may also maintain survival and expansion of the primary tumor.

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.

With its particular emphasis on the constitutive activity of G-protein-coupled receptors (GPCRs)s, this book comprehensively discusses an important biological process that has not yet been covered in such depth in any other existing books on GPCRs. The international team of highly distinguished authors addresses in detail current models and concepts, to introduce medicinal chemists, physiologists, pharmacologists, and medical researchers into the advances in the understanding of GPCR activation and constitutive activity. In addition, the book provides an overview on methods of investigating constitutive GPCR activity. The text is well illustrated by selected experimental data and schemes._The chaptes are all cross-referenced with each other and cover general mechnisms, methodological approaches and cover selected important GPCR sysstems, the consequences for drug action, including, side effects, and rational drug design for GPCR targets. A highly recommended reference for researchers in academia and industry. authors addresses in detail current models and concepts, so as to introduce pharmaceutical chemists, physiologists and medical researchers to the advances in the understanding of GPCR activation and constitutive activity, and provides an overview of the methods of investigating GPCR activity. The text is backed by abundant case studies and methodological advice for analyzing GPCRs, covering selected pharmacologically relevant GPCR systems, the consequences for drug action, including unwanted side effects, and rational drug design for GPCR targets. A highly practical reference for researchers in academia and industry.

Chemokine Receptors and NeuroAIDS: Beyond the Co-receptor Function and Links to Other Neuropathologies focuses on unresolved or emerging issues concerning the role of chemokine receptors in neuronal injury and HIV neuropathology, including their ability to regulate fundamental neuronal and glial functions and their role in neurovirulence and neurotoxicity. Although the importance of these molecules in the CNS physiology and pathology is now apparent, these issues are still matter of debate, and further research is required to design effective pharmacological agents that specifically target the brain chemokine system without major side effects. To this end, specific topics have been selected and are reviewed by international experts within the basic science/medical community. This book encourages investigation in the most controversial areas and fosters interaction between clinicians and basic scientists. The book also increases awareness about differences in disease progression among different parts of the world as well as selected patient populations, which may also help identifying novel therapeutic strategies.

The G protein-coupled receptors (GPCRs) and associated peripheral G proteins underpin a multitude of physiological processes. The GPCRs represent one of the largest superfamilies in the human genome and are a significant target for bioactive and drug discovery programs. It is estimated that greater than 50% of all drugs, including those in development, currently target GPCRs. Many of the characterized GPCRs have known ligands; however, approximately 20% of GPCRs are described as orphan GPCRs, apparent GPCRs that share the generic high-level structure charact- istic of GPCRs but whose endogenous ligand is not known. Therefore, it is expected that the field of GPCR drug discovery and development will greatly expand in the coming years with emphasis on new generations of drugs against GPCRs with unique therapeuticuseswhichmayincludedrugssuchasallostericregulators,inverseagonists, and identification of orphan GPCR ligands. AswelearnmoreaboutthemolecularsignalingcascadesfollowingGPCRactivation, we acquire a better appreciation of the complexity of cell signaling and as a result, also acquire a vast array ofnew molecularmethods toinvestigate these andother processes. Thegeneralaimofthisbookistoprovideresearcherswitharangeofprotocolsthatmay be useful in their GPCR drug discovery programs. It is also the basis for the devel- ment of future assays in this field. Therefore, the range of topics covered and the appropriate methodological approaches in GPCR drug discovery are reflected in this book. Itisinterestingtonotethatfuturedirectionsindrugdiscoverywillrequireinput and collaboration from a plethora of fields of research. As such, this book will likely be of interest to scientists involved in such fields as molecular biology, pharmacology, biochemistry, cellular signaling, and bio-nanotechnology.

Learn all the microbiology and basic immunology concepts you need to know for your courses and exams. Now fully revised and updated, Mims’ clinically relevant, systems-based approach and abundant colour illustrations make this complex subject easy to understand and remember. Learn about infections in the context of major body systems and understand why these are environments in which microbes can establish themselves, flourish, and give rise to pathologic changes. This systems-based approach to microbiology employs integrated and case-based teaching that places the ‘bug parade’ into a clinical context. Effectively review for problem-based courses with the help of chapter introductions and ‘Lessons in Microbiology’ text boxes that highlight the clinical relevance of the material, offer easy access to key concepts, and provide valuable review tools. Approach microbiology by body system or by pathogen through the accompanying electronic ‘Pathogen Parade’ – a quickly searchable, cross-referenced glossary of viruses, bacteria and fungi A new electronic ‘Vaccine Parade’ offers quick-reference coverage of the most commonly used vaccines in current clinical practice Deepen your understanding of epidemiology and the important role it plays in providing evidence-based identification of key risk factors for disease and targets for preventative medicine. Grasp and retain vital concepts easily, with a user-friendly colour coded format, succinct text, key concept boxes, and dynamic illustrations. New and enhanced information reflects the growing importance of the human microbiota and latest molecular approaches Access the complete contents on the go via the accompanying interactive eBook, with a range of bonus materials to enhance learning and retention – includes self-assessment materials and clinical cases to check your understanding and aid exam preparation.