Allosterism in Drug Discovery

Author: Dario Doller
Publisher: Royal Society of Chemistry
ISBN: 1782629270
Format: PDF, Docs
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Although the concept of allosterism has been known for over half a century, its application in drug discovery has exploded in recent years. The emergence of novel technologies that enable molecular-level ligand-receptor interactions to be studied in studied in unprecedented detail has driven this trend. This book, written by the leaders in this young research area, describes the latest developments in allosterism for drug discovery. Bringing together research in a diverse range of scientific disciplines, Allosterism in Drug Discovery is a key reference for academics and industrialists interested in understanding allosteric interactions. The book provides an in-depth review of research using small molecules as chemical probes and drug candidates that interact allosterically with proteins of relevance to life sciences and human disease. Knowledge of these interactions can then be applied in the discovery of the novel therapeutics of the future. This book will be useful for people working in all disciplines associated with drug discovery in academia or industry, as well as postgraduate students who may be working in the design of allosteric modulators.

Discovery of Hidden Allosteric Sites as Novel Targets for Allosteric Drug Design

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ISBN:
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Highlights: Hidden allosteric sites provide valuable avenues for allosteric drug discovery. Hidden allosteric sites are invisible in the ligand-unbound crystal structures. Identification of hidden allosteric sites is a profound challenge. Methods for the identification of hidden allosteric sites are reviewed. Potential statics to future discovery of hidden allosteric sites are discussed. Abstract : Hidden allosteric sites, as a novel type of allosteric site, are invisible in ligand-unbound (apo) crystal structures, but can emerge in ligand-bound (holo) crystal structures when a specific ligand binds to, and stabilizes, a unique conformation favored by the ligand. However, the identification of these sites is a significant challenge. Several computational and experimental approaches have been developed to identify such sites in proteins. Here, we outline these approaches, with a focus on examples of the successful use of such techniques. The discovery of hidden allosteric sites offers a new avenue for facilitating drug design by greatly expanding the repertoire of available drug targets, contributing to the search for allosteric drugs for the treatment of human diseases.

Fragment Based Drug Discovery

Author: Steven Howard
Publisher: Royal Society of Chemistry
ISBN: 1849739080
Format: PDF, ePub, Mobi
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Fragment-based drug discovery is a rapidly evolving area of research, which has recently seen new applications in areas such as epigenetics, GPCRs and the identification of novel allosteric binding pockets. The first fragment-derived drug was recently approved for the treatment of melanoma. It is hoped that this approval is just the beginning of the many drugs yet to be discovered using this fascinating technique. This book is written from a Chemist's perspective and comprehensively assesses the impact of fragment-based drug discovery on a wide variety of areas of medicinal chemistry. It will prove to be an invaluable resource for medicinal chemists working in academia and industry, as well as anyone interested in novel drug discovery techniques.

Pharmacology in Drug Discovery

Author: Terrence P. Kenakin
Publisher: Academic Press
ISBN: 0123848563
Format: PDF, Docs
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Pharmacology in Drug Discovery: Understanding Drug Response is designed for all students, recent graduates, and new researchers in the pharmaceutical and biotechnology industries who need to interpret change in physiology induced by a chemical substance. Physiological systems customize chemical signal input to their own needs; therefore the same drug can have different effects in different physiological systems. The field of pharmacology is unique in that it furnishes the tools to analyze these different behaviors and traces them to their root cause. This enables predictions of drug behavior to be made in all systems, an invaluable tool for drug discovery because almost all drugs are developed in test systems far removed from the therapeutic one. This valuable resource provides simple explanations of the ways in which biological systems use basic biochemical mechanisms to produce fine chemical control of physiology, allowing for more informed predictions of drug effects in all systems and forming the basis of the drug-discovery process. Chapters follow a logical progression on how to characterize the pharmacology of any given molecule, and include important terminology, chapter summaries, references, and review questions to aid the reader in understanding and retention of the material. Enables the reader to interpret drug dose-response data and make mechanistic inferences at the molecular level Bridges the gap between biochemistry and therapeutic medicine Chapters include key topics such as drug affinity and efficacy, enzymes as drug targets, in vivo pharmacology, safety pharmacology, and more

Allosteric Receptor Modulation in Drug Targeting

Author: Norman G. Bowery
Publisher: CRC Press
ISBN: 9781420016185
Format: PDF, ePub
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Offering a wide array of illustrations and tables in every chapter, this book extensively covers the principles of allosterism in reference to drug action and progresses to a detailed examination of individual ionotropic and G-protein coupled receptor systems-helping those new to the subject understand the importance of allosterism and providing those already working in the field with specific reference information. This title provides in-depth chapters on basic principles of allosterism and its significance at GABAA, 5HT3, nicotinic, and GABAB receptors, ionotropic and metabotropic receptors for glutamate, muscarinic receptors and alpha 2 adrenoceptors to provide a firm foundation to the subject.

Oligomerization and Allosteric Modulation in G Protein Coupled Receptors

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Publisher: Academic Press
ISBN: 012394791X
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In this thematic volume of Progress in Molecular Biology and Translational Science, researchers reflect on recent developments and research surrounding G protein-coupled receptors. The chapters cover a large breadth of research, including GPCR role in stem cell function and pharmacology. Authors explore in-depth research techniques and applications of GPCR usage, covering theory, laboratory approaches, and unique qualities that make GPCRs a crucial tool in microbiological and cancer research. Contributions from leading authorities Informs and updates on all the latest developments in the field

Quantitative Molecular Pharmacology and Informatics in Drug Discovery

Author: Michael Lutz
Publisher: John Wiley & Sons
ISBN: 9780471988618
Format: PDF, Mobi
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Quantitative Molecular Pharmacology and Informatics in Drug Discovery Michael Lutz, Section Head, Cheminformatics Group and Terry Kenakin, Principal Research Scientist, Glaxo Wellcome Research and Development, Research Triangle Park, NC, USA Quantitative Molecular Pharmacology and Informatics in Drug Discovery combines pharmacology, genetics and statistics to provide a complete guide to the modern drug discovery process. The book discusses the pharmacology of drug testing and provides a detailed description of the statistical methods used to analyze the resulting data. Application of genetic and genomic tools for identification of biological targets is reviewed in the context of drug discovery projects. Covering both the theoretical principles upon which the techniques are based and the practicalities of drug discovery, this informative guide. ∗ outlines in step–by–step detail the advantages and disadvantages of each technology and approach and links these to the type of chemical target being sought after in the drug discovery process; and, ∗ provides excellent demonstrations of how to use powerful pharmacological and statistical tools to optimize high–throughput screening assays. Written by two internationally known and well–regarded experts, this book is an essential reference for research and development scientists working in the pharmaceutical and biotechnology industries. It will also be useful for postgraduates studying pharmacology and applied statistics.

Biomolecular Simulations in Drug Discovery

Author: Francesco L. Gervasio
Publisher: Wiley-VCH
ISBN: 3527342656
Format: PDF, Kindle
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A timely and topical survey of modern simulation tools and their applications in real-life drug discovery, allowing for better and quicker results in structure-based drug design. The first part of this practical guide for industry professionals describes common tools used in the biomolecular simulation of drugs and their targets. A critical analysis of the accuracy of the predictions, the integration of modeling with other experimental data combined with numerous case studies from different therapeutic fields enable users to quickly adopt these new methods for their current projects. The second part then shows how these tools can be applied to drug discovery and development projects. Modeling experts from the pharmaceutical industry and from leading academic institutions present real-life examples for important target classes such as GPCRs, kinases and amyloids as well as for common challenges in structure-based drug discovery. With its inclusion of novel methods and strategies for the modeling of drug-target interactions in the framework of real-life drug discovery and development, this application-oriented reference is tailor-made for medicinal chemists and those working in the pharmaceutical industry.

Drug Discovery Strategies and Methods

Author: Alexandros Makriyannis
Publisher: CRC Press
ISBN: 082475767X
Format: PDF, Mobi
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Navigate the complex and multidisciplinary path of drug discovery procedures with Drug Discovery Strategies and Methods-a well-organized and timely reference that analyzes methods in target identification and validation, lead detection, compound optimization, and biological testing. This volume addresses challenges encountered during the discovery of new pharmaceutical candidates including the use of cutting-edge techniques utilized in drug design and development. It considers key elements in the drug design cycle ranging from appropriateness of targets and disease models to compound characterization, safety, and efficacy and the role of protein crystallography in structure-based drug design.

Multifaceted Roles of Crystallography in Modern Drug Discovery

Author: Giovanna Scapin
Publisher: Springer
ISBN: 9401797196
Format: PDF, Kindle
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The present work offers a snapshot of the state-of-the-art of crystallographic, analytical, and computational methods used in modern drug design and development. Topics discussed include: drug design against complex systems (membrane proteins, cell surface receptors, epigenetic targets, and ribosomes); modulation of protein-protein interactions; the impact of small molecule structures in drug discovery and the application of concepts such as molecular geometry, conformation, and flexibility to drug design; methodologies for understanding and characterizing protein states and protein-ligand interactions during the drug design process; and monoclonal antibody therapies. These methods are illustrated through their application to problems of medical and biological significance, such as viral and bacterial infections, diabetes, autoimmune disease, and CNS diseases. As approaches to drug discovery have changed over time, so have the methodologies used to solve the varied, new, and difficult problems encountered in drug discovery. In recent years we have seen great progress in the fields of genetics, biology, chemistry, and medicine, but there are still many unmet medical needs, from bacterial infections to cancer to chronic maladies, that require novel, different, or better therapies. This work will be of interest to researchers and policy makers interested in the latest developments in drug design.