From Structure to Clinical Development: Allosteric Modulation of G Protein-Coupled Receptors
From Structure to Clinical Development: Allosteric Modulation of G Protein-Coupled Receptors

Author:

Publisher: Academic Press

Published: 2020-05-13

Total Pages: 330

ISBN-13: 0128201886

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From Structure to Clinical Development: Allosteric Modulation of G Protein-Coupled Receptors, Volume 88, the latest release in the Advances in Pharmacology series, presents a variety of chapters from the best authors in the field. Chapters in this updated edition include Targeting muscarinic M1 receptor in neurodegeneration, Photo-switchable allosteric ligands, Computational approaches for the design of mGlu receptor allosteric modulators, Allosteric modulation of GLP-1 receptor in metabolic disorders, Group II mGluR roles in the nervous system and their roles in addiction, RAMPs as allosteric modulators of Class B GPCRs, Structure-based discovery and development of mGlu5 NAMs, and much more. - Includes the authority and expertise of leading contributors in pharmacology - Presents the latest release in the Advances in Pharmacology series

Allosteric Modulation of G Protein-Coupled Receptors
Allosteric Modulation of G Protein-Coupled Receptors

Author: Robert Laprairie

Publisher: Academic Press

Published: 2022-02-05

Total Pages: 214

ISBN-13: 0128197722

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Allosteric Modulation of G Protein-Coupled Receptors reviews fundamental information on G protein-coupled receptors (GPCRs) and allosteric modulation, presenting original research in the area and collectively providing a comprehensive description of key issues in GPCR allosteric modulation. The book provides background on core concepts of molecular pharmacology while also introducing the most important advances and studies in the area. It also discusses key methodologies. This is an essential book for researchers and advanced students engaged in pharmacology, toxicology and pharmaceutical sciences training and research. Many of the GPCR-targeted drugs released in the past decade have specifically worked via allosteric mechanisms. Unlike direct orthosteric-acting compounds that occupy a similar receptor site to that of endogenous ligands, allosteric modulators alter GPCR-dependent signaling at a site apart from the endogenous ligand. Recent methodological and analytical advances have greatly improved our ability to understand the signaling mechanisms of GPCRs. We now know that allostery is a common regulatory mechanism for all GPCRs and not – as we once believed – unique to a few receptor subfamilies. - Introduces background on core concepts of molecular pharmacology, including statistical analyses, non-linear regression, complex models and GPCR-dependent signal transduction as they relate to allosteric modulation - Discusses critical advances and landmark studies, including discoveries in the area of GPCR allosteric modulation, which are reviewed for their importance in positive and negative regulation, protein-protein interactions, and small molecule drug discovery - Includes key methodologies used to study allosteric modulation at the in silico, in vitro, and in vivo levels of drug discovery and characterization

Protein Allostery in Drug Discovery
Protein Allostery in Drug Discovery

Author: Jian Zhang

Publisher: Springer Nature

Published: 2019-11-09

Total Pages: 386

ISBN-13: 9811387192

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The book focuses on protein allostery in drug discovery. Allosteric regulation, ʹthe second secret of lifeʹ, fine-tunes virtually most biological processes and controls physiological activities. Allostery can both cause human diseases and contribute to development of new therapeutics. Allosteric drugs exhibit unparalleled advantages compared to conventional orthosteric drugs, rendering the development of allosteric modulators as an appealing strategy to improve selectivity and pharmacodynamic properties in drug leads. The Series delineates the immense significance of protein allostery—as demonstrated by recent advances in the repertoires of the concept, its mechanistic mechanisms, and networks, characteristics of allosteric proteins, modulators, and sites, development of computational and experimental methods to predict allosteric sites, small-molecule allosteric modulators of protein kinases and G-protein coupled receptors, engineering allostery, and the underlying role of allostery in precise medicine. Comprehensive understanding of protein allostery is expected to guide the rational design of allosteric drugs for the treatment of human diseases. The book would be useful for scientists and students in the field of protein science and Pharmacology etc.

Allosterism in Drug Discovery
Allosterism in Drug Discovery

Author: Dario Doller

Publisher: Royal Society of Chemistry

Published: 2016-11-24

Total Pages: 458

ISBN-13: 1782624597

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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.

GPCR Molecular Pharmacology and Drug Targeting
GPCR Molecular Pharmacology and Drug Targeting

Author: Annette Gilchrist

Publisher: John Wiley & Sons

Published: 2010-12-10

Total Pages: 675

ISBN-13: 1118035178

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G protein-coupled receptors (GPCRs) are a large protein family of transmembrane receptors vital in dictating cellular responses. GPCRs are involved in many diseases, but are also the target of around half of all modern medicinal drugs. Shifting Paradigms in G Protein Coupled Receptors takes a look at the way GPCRs are examined today, how they react, how their mutations lead to disease, and the many ways in which they can be screened for compounds that modulate them. Chemists, pharmacologists, and biologists will find essential information in this comprehensive reference.

Computational Methods for GPCR Drug Discovery
Computational Methods for GPCR Drug Discovery

Author: Alexander Heifetz

Publisher: Humana Press

Published: 2017-11-30

Total Pages: 436

ISBN-13: 9781493974641

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This volume looks at modern computational strategies and techniques used in GPCR drug discovery including structure and ligand-based approaches and cheminformatics. The chapters in this book describe how these approaches can be applied to address key drug discovery issues, such as receptor structure modelling, function and dynamics, prediction of protein-water-ligand interactions and binding kinetics, free energy of binding, interconversion between agonists and antagonists, deorphanization of GPCRs, and the discovery of biased and allosteric modulators. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary software and tools, step-by-step, readily reproducible modelling protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and unique,Computational Methods for GPCR Drug Discovery is a valuable resource for structural and molecular biologists, computational and medicinal chemists, pharmacologists, and drug designers.

Myeloid Cells in Health and Disease
Myeloid Cells in Health and Disease

Author: Siamon Gordon

Publisher: John Wiley & Sons

Published: 2020-07-10

Total Pages: 892

ISBN-13: 1555819192

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The structure, functions, and interactions of myeloid cells have long been the focus of research and therapeutics development. Yet, much more remains to be discovered about the complex web of relationships that makes up the immune systems of animals. Scientists today are applying genome-wide analyses, single-cell methods, gene editing, and modern imaging techniques to reveal new subclasses of differentiated myeloid cells, new receptors and cytokines, and important interactions among immune cells. In Myeloid Cells in Health and Disease: A Synthesis, Editor Siamon Gordon has assembled an international team of esteemed scientists to provide their perspectives of myeloid cells during innate and adaptive immunity. The book begins by presenting the foundational research of Paul Ehrlich, Elie Metchnikoff, and Donald Metcalf. The following chapters discuss evolution and the life cycles of myeloid cells; specific types of differentiated myeloid cells, including macrophage differentiation; and antigen processing and presentation. The rest of the book is organized by broad topics in immunology, including the recruitment of myeloid and other immune cells following microbial infection the role of myeloid cells in the inflammation process and the repair of damaged tissue the vast arsenal of myeloid cell secretory molecules, including metalloproteinases, tumor necrosis factor, histamine, and perforin receptors and downstream signaling pathways that are activated following ligand-receptor binding roles of myeloid cells during microbial and parasite infections contributions of myeloid cells in atherosclerosis myeloid-derived suppressor cells in tumor development and cancer Myeloid Cells in Health and Disease: A Synthesis will benefit graduate students and researchers in immunology, hematology, microbial pathogenesis, infectious disease, pathology, and pharmacology. Established scientists and physicians in these and related fields will enjoy the book's rich history of myeloid cell research and suggestions for future research directions and potential therapies.

Structural Biology in Drug Discovery
Structural Biology in Drug Discovery

Author: Jean-Paul Renaud

Publisher: John Wiley & Sons

Published: 2020-01-09

Total Pages: 1437

ISBN-13: 1118900502

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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

Biomolecular Simulations in Structure-Based Drug Discovery
Biomolecular Simulations in Structure-Based Drug Discovery

Author: Francesco L. Gervasio

Publisher: John Wiley & Sons

Published: 2019-04-29

Total Pages: 368

ISBN-13: 3527342656

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A guide to applying the power of modern simulation tools to better drug design Biomolecular Simulations in Structure-based Drug Discovery offers an up-to-date and comprehensive review of modern simulation tools and their applications in real-life drug discovery, for better and quicker results in structure-based drug design. The authors describe common tools used in the biomolecular simulation of drugs and their targets and offer an analysis of the accuracy of the predictions. They also show how to integrate modeling with other experimental data. Filled with numerous case studies from different therapeutic fields, the book helps professionals to quickly adopt these new methods for their current projects. Experts from the pharmaceutical industry and academic institutions present real-life examples for important target classes such as GPCRs, ion channels and amyloids as well as for common challenges in structure-based drug discovery. Biomolecular Simulations in Structure-based Drug Discovery is an important resource that: -Contains a review of the current generation of biomolecular simulation tools that have the robustness and speed that allows them to be used as routine tools by non-specialists -Includes information on the novel methods and strategies for the modeling of drug-target interactions within the framework of real-life drug discovery and development -Offers numerous illustrative case studies from a wide-range of therapeutic fields -Presents an application-oriented reference that is ideal for those working in the various fields Written for medicinal chemists, professionals in the pharmaceutical industry, and pharmaceutical chemists, Biomolecular Simulations in Structure-based Drug Discovery is a comprehensive resource to modern simulation tools that complement and have the potential to complement or replace laboratory assays for better results in drug design.