Backed by leading authorities, this is a professional guide to successful compound screening in pharmaceutical research and chemical biology, including the chemoinformatic tools needed for correct data evaluation. Chapter authors from leading pharmaceutical companies as well as from Harvard University discuss such factors as chemical genetics, binding, cell-based and biochemical assays, the efficient use of compound libraries and data mining using cell-based assay results. For both academics and professionals in the pharma and biotech industries working on small molecule screening.
The development of suitable assays, the integration of appropriate technology, and the effective management of the essential infrastructure are all critical to the success of any high-throughput screening (HTS) endeavor. However, few scientists have the multidisciplinary experience needed to control all aspects of an HTS drug discovery project. A Practical Guide to Assay Development and High-Throughput Screening in Drug Discovery integrates the experience of diverse experts who offer fundamental and practical guidance across numerous situations. The book first discusses assay developments for important target classes such as protein kinases and phosphatases, proteases, nuclear receptors, G protein-coupled receptors, ion channels, and heat shock proteins. It next examines assay developments for cell viability, apoptosis, and infectious diseases. The contributors explore the application of emerging technologies and systems, including image-based high content screening, RNA interference, and primary cells. Finally, they discuss the essential components of the integrated HTS process, such as screening automation, compound library management, the screening of natural products from botanical sources, and screening informatics. Designed to motivate researchers to bring further advances to the field, this volume provides practical guidance on how to initiate, validate, optimize, and manage a bioassay intended to screen large collections of compounds. Drawing on the knowledge from experts actively involved in assay development and HTS, this is a resource that is both comprehensive and focused.
Furnishing the latest interdisciplinary information on the most important and frequently the only investigational system available for discovery programs that address the effects of small molecules on newly discovered enzyme and receptor targets emanating from molecular biology, this timely resource facilitates the transition from classical to high throughput screening (HTS) systems and provides a solid foundation for the implementation and development of HTS in bio-based industries and associated academic environments.
High Throughput Analysis for Early Drug Discovery offers concise and unbiased presentations by synthetic and analytical chemists who have been involved in creating and moving the field of combinatorial chemistry into the academic and industrial mainstream. Since the synthetic method often dictates the appropriate types of analysis, each chapter or section begins with a description of the synthesis approach and its advantages. The description of various combinatorial and high-throughput parallel synthesis techniques provide a relevant point of entry for synthetic chemists who need to set up appropriate characterisation methods for his/her organisation. This is an invaluable resource for all organic and analytical chemists in the pharmaceutical, agrochemical, and biotechnology fields who are either involved in, or beginning to investigate combinatorial techniques to increase overall efficiency and productivity. First reference to focus on the analytical side of synthesis
The continued successes of large- and small-scale genome sequencing projects are increasing the number of genomic targets available for drug d- covery at an exponential rate. In addition, a better understanding of molecular mechanisms—such as apoptosis, signal transduction, telomere control of ch- mosomes, cytoskeletal development, modulation of stress-related proteins, and cell surface display of antigens by the major histocompatibility complex m- ecules—has improved the probability of identifying the most promising genomic targets to counteract disease. As a result, developing and optimizing lead candidates for these targets and rapidly moving them into clinical trials is now a critical juncture in pharmaceutical research. Recent advances in com- natorial library synthesis, purification, and analysis techniques are not only increasing the numbers of compounds that can be tested against each specific genomic target, but are also speeding and improving the overall processes of lead discovery and optimization. There are two main approaches to combinatorial library production: p- allel chemical synthesis and split-and-mix chemical synthesis. These approaches can utilize solid- or solution-based synthetic methods, alone or in combination, although the majority of combinatorial library synthesis is still done on solid support. In a parallel synthesis, all the products are assembled separately in their own reaction vessels or microtiter plates. The array of rows and columns enables researchers to organize the building blocks to be c- bined, and provides an easy way to identify compounds in a particular well.
This first comprehensive book on heterogeneous catalysis provides an up-to-date overview of the current status and advances being made in this rapidly growing field. The authors from both academia and industry apply HTS to the discovery and optimization of complex multi-component heterogeneous catalysts and electrocatalysts, while also analyzing its capabilities and limitations. They also include CombiCatalysis, screening and optimization strategies, as well as aspects of electrocatalysis, and make use of various industrial methodologies, such as those of Avantium, H.T.E., Symyx, Sintef and IMM, to demonstrate the various approaches to overcoming the challenges of miniaturization. The text is supported throughout by numerous tables, illustrations, graphs, and photographs of synthesis and reactor equipment, most of them in color. For advanced students, catalytic or solid-state chemists in R&D and engineers specializing in reactor technology, detection schemes and automation.
Catalysts are central in modern industrial chemistry and there is an urgent need to develop new catalysts. Such a rapid pace of development brings with it a new set of challenges at all levels of research, from synthesis and characterization to testing and modelling. This book reviews the current status of combinatorial catalysis, scientific catalyst design techniques, methods for preparing inorganic combinatorial libraries, experimental design methods, data processing, system modelling an simulation, and catalyst testing. The individual contributions reveal the development of high throughput catalyst design and test methods and identify the main challenges in the field, including new catalyst preparation techniques, rapid performance evaluation, and new microreactor configurations. Readership: All those working in catalytic process analysis and development. The extensive review of catalysis principles is especially relevant for postgraduate students seeking to pursue studies in catalysis.
Based on the international workshop on 'Small Molecule - Protein Interactions' held in Berlin, April 24-26, 2002, researchers from industry and academic laboratories describe novel and efficient ways selecting promising new drug targets and developing small molecule inhibitors against them. The structure of the book corresponds to the different aspects of the drug discovery process. All chapters are written by leading experts in the field, who present and discuss the most recent state-of-the-art tools and techniques for the development of novel drugs. The value of the book lies in surveying and summarizing the approaches taken by different companies and institutions giving the reader a balanced view on the use of the latest techniques on the one hand and experience-based assistance in selecting appropriate tools for their own work on the other hand.
Chemoinformatics is equipped to impact our life in a big way mainly in the fields of chemical, medical and material sciences. This book is a product of several years of experience and passion for the subject written in a simple lucid style to attract the interest of the student community who wish to master chemoinformatics as a career. The topics chosen cover the entire spectrum of chemoinformatics activities (methods, data and tools). The algorithms, open source databases, tutorials supporting theory using standard datasets, guidelines, questions and do it yourself exercises will make it valuable to the academic research community. At the same time every chapter devotes a section on development of new software tools relevant for the growing pharmaceutical, fine chemicals and life sciences industry. The book is intended to assist beginners to hone their skills and also constitute an interesting reading for the experts.
As the use of high-throughput screening expands and creates more interest in the academic community, the need for detailed reference materials becomes ever more pressing. Cell-Based Assays for High-Throughput Screening: Methods and Protocols aims to fill an important part of this need by providing an easily accessible reference volume for cell-based phenotypic screening. Leading researchers in the field contribute state-of-the-art methods with actionable protocols covering four major areas of study: model biological systems, screening modalities and assay systems, detection technologies, and approaches to data analysis. Written in the highly successful Methods in Molecular BiologyTM series format, each chapter includes a brief introduction to the subject, lists of necessary materials and reagents, step-by-step laboratory protocols, and a Notes section detailing tips on troubleshooting and avoiding known pitfalls. Cutting-edge and easy-to-use, Cell-Based Assays for High-Throughput Screening: Methods and Protocols presents an overview of relevant approaches, enabling the direct application of existing methods to new discoveries while also inspiring researchers to approach their screening projects in a conceptually modular fashion, enhancing the power to discover through new combinations of existing approaches.
