This book aims to provide a brief update on the functions of purinergic receptors in various systems, in addition to the signaling pathway activated to mediate these functions. We address the influence of hypoxia by modulating the activity of these receptors under physiological and pathophysiological conditions. Additionally, we describe the mechanisms of induction of pain and inflammation in different systems. Finally, the book discusses some of the main bioinformatics tools currently used to improve or discover new prototypes capable of selectively acting on these receptors with estimated parameters of satisfactory solubility and toxicity for possible commercial implementation.

Vols. for 1963- include as pt. 2 of the Jan. issue: Medical subject headings.

The endothelium, a monolayer of endothelial cells, constitutes the inner cellular lining of the blood vessels (arteries, veins and capillaries) and the lymphatic system, and therefore is in direct contact with the blood/lymph and the circulating cells. The endothelium is a major player in the control of blood fluidity, platelet aggregation and vascular tone, a major actor in the regulation of immunology, inflammation and angiogenesis, and an important metabolizing and an endocrine organ. Endothelial cells controls vascular tone, and thereby blood flow, by synthesizing and releasing relaxing and contracting factors such as nitric oxide, metabolites of arachidonic acid via the cyclooxygenases, lipoxygenases and cytochrome P450 pathways, various peptides (endothelin, urotensin, CNP, adrenomedullin, etc.), adenosine, purines, reactive oxygen species and so on. Additionally, endothelial ectoenzymes are required steps in the generation of vasoactive hormones such as angiotensin II. An endothelial dysfunction linked to an imbalance in the synthesis and/or the release of these various endothelial factors may explain the initiation of cardiovascular pathologies (from hypertension to atherosclerosis) or their development and perpetuation. Table of Contents: Introduction / Multiple Functions of the Endothelial Cells / Calcium Signaling in Vascular Cells and Cell-to-Cell Communications / Endothelium-Dependent Regulation of Vascular Tone / Conclusion / References

This is an overview of the fast-moving field of purinergic signalling through adenosine and ATP receptors. - Authors are the leading authorities in their fields - Subject matter is important for understanding tissue protection - Subject matter is of intense interest for new drug development

With the most comprehensive and up-to-date overview of structure-based drug discovery covering both experimental and computational approaches, Structural Biology in Drug Discovery: Methods, Techniques, and Practices describes principles, methods, applications, and emerging paradigms of structural biology as a tool for more efficient drug development. Coverage includes successful examples, academic and industry insights, novel concepts, and advances in a rapidly evolving field. The combined chapters, by authors writing from the frontlines of structural biology and drug discovery, give readers a valuable reference and resource that: Presents the benefits, limitations, and potentiality of major techniques in the field such as X-ray crystallography, NMR, neutron crystallography, cryo-EM, mass spectrometry and other biophysical techniques, and computational structural biology Includes detailed chapters on druggability, allostery, complementary use of thermodynamic and kinetic information, and powerful approaches such as structural chemogenomics and fragment-based drug design Emphasizes the need for the in-depth biophysical characterization of protein targets as well as of therapeutic proteins, and for a thorough quality assessment of experimental structures Illustrates advances in the field of established therapeutic targets like kinases, serine proteinases, GPCRs, and epigenetic proteins, and of more challenging ones like protein-protein interactions and intrinsically disordered proteins

Frontiers in Cardiovascular Drug Discovery is a book series devoted to publishing the latest advances in cardiovascular drug design and discovery. Each volume brings reviews on the biochemistry, in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, recent important patents, and structure-activity relationships of molecules used in cardiovascular therapy. The book series should prove to be of great interest to all medicinal chemists and pharmaceutical scientists involved in preclinical and clinical research in cardiology. Volume 6 covers the following topics: - Cardiovascular effects of ranolazine and the scope for translational research: a current review of literature - Rho/Rho kinase signaling pathway and disease: - Hibernation or transformation? Challenges in cardiovascular drug development - New approaches in P2Y12 receptor blocker drugs use - Pathophysiological links between diabetes and cardiovascular diseases: at the biochemical and molecular levels

Since their discovery approximately 25 years ago, adenosine receptors have now emerged as important novel molecular targets in disease and drug discovery. These proteins play important roles in the entire spectrum of disease from inflammation to immune suppression. Because of their expression on a number of different cell types and in a number of different organ systems they play important roles in specific diseases, including asthma, rheumatoid arthritis, Parkinson’s disease, multiple sclerosis, Alzheimer’s disease, heart disease, stroke, cancer, sepsis, and obesity. As a result of intense investigations into understanding the molecular structures and pharmacology of these proteins, new molecules have been synthesized that have high specificity for these proteins and are now entering clinical trials. These molecules will define the next new classes of drugs for a number of diseases with unmet medical needs.