Optimization In Drug Discovery

Author : Gary W. Caldwell,Zhengyin Yan
Publisher : Humana
Page : 0 pages
File Size : 50,5 Mb
Release : 2016-08-23
Category : Medical
ISBN : 1493960709

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Optimization in Drug Discovery by Gary W. Caldwell,Zhengyin Yan Pdf

Thoroughly revised and updated, Optimization in Drug Discovery: In Vitro Methods, Second Edition presents a wide spectrum of in vitro assays including formulation, plasma binding, absorption and permeability, cytochrome P450 (CYP) and UDP-glucuronosyltransferases (UGT) metabolism, CYP inhibition and induction, drug transporters, drug-drug interactions via assessment of reactive metabolites, genotoxicity, and chemical and photo-mutagenicity assays. Written for the Methods in Pharmacology and Toxicology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and tips on troubleshooting and avoiding known pitfalls. Expert authors have developed and utilized these in vitro assays to achieve “drug-like” characteristics in addition to efficacy properties and good safety profiles of drug candidates. Comprehensive and up-to-date, Optimization in Drug Discovery: In Vitro Methods, Second Edition aims to guide researchers down the difficult path to successful drug discovery and development.

Author : Tushar Kshirsagar
Publisher : CRC Press
Page : 256 pages
File Size : 49,8 Mb
Release : 2008-03-04
Category : Medical
ISBN : 9781420006964

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High-Throughput Lead Optimization in Drug Discovery by Tushar Kshirsagar Pdf

A Single Source on Parallel Synthesis for Lead Optimization The end of the previous millennium saw an explosion in the application of parallel synthesis techniques for making compounds for high-throughput screening. Over time, it became clear that more thought in the design phase of library development is necessary to generate high qualit

Author : Ph.D., Jeffrey S. Handen
Publisher : CRC Press
Page : 310 pages
File Size : 53,6 Mb
Release : 2005-05-26
Category : Medical
ISBN : 9781420028072

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Industrialization of Drug Discovery by Ph.D., Jeffrey S. Handen Pdf

The drug discovery and development process is getting longer, more expensive, and no better. The industry suffers from the same clinical attrition and safety-related market withdrawal rates today as it did 20 years ago. Industrialization of Drug Discovery: From Target Selection Through Lead Optimization scrutinizes these problems in detail, contras

Author : Bernard Testa
Publisher : John Wiley & Sons
Page : 678 pages
File Size : 51,7 Mb
Release : 2001-03-26
Category : Medical
ISBN : 3906390225

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Pharmacokinetic Optimization in Drug Research by Bernard Testa Pdf

The optimization of pharmacokinetic properties has become the bottleneck and a major challenge in drug research. There was, hence, an urgent need for a book covering this field in an authoritative, comprehensive, factual, and conceptual manner. In this work of unique breadth and depth, international authorities and practicing experts from academia and industry present the most modern biological, physicochemical, and computational strategies to achieve optimal pharmacokinetic properties in research series. These properties include gastrointestinal absorption, protein binding, brain permeation, and metabolic profile. Toxicological issues are, of course, also of utmost importance. In addition to its 33 chapters, the book includes a CD-ROM containing the invited lectures, oral communications and posters (in full version) presented at the Second LogP Symposium, 'Lipophilicity in Drug Disposition -- Practical and Computational Approaches to Molecular Properties Related to Drug Permeation, Disposition and Metabolism', held at the University of Lausanne in March 2000.n̓.

Author : Yan
Publisher : Unknown
Page : 436 pages
File Size : 53,7 Mb
Release : 2009-12-01
Category : Electronic
ISBN : 8184894848

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Optimization In Drug Discovery by Yan Pdf

Author : Li Di,Edward H Kerns
Publisher : Elsevier
Page : 549 pages
File Size : 49,9 Mb
Release : 2010-07-26
Category : Science
ISBN : 9780080557618

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Drug-like Properties: Concepts, Structure Design and Methods by Li Di,Edward H Kerns Pdf

Of the thousands of novel compounds that a drug discovery project team invents and that bind to the therapeutic target, typically only a fraction of these have sufficient ADME/Tox properties to become a drug product. Understanding ADME/Tox is critical for all drug researchers, owing to its increasing importance in advancing high quality candidates to clinical studies and the processes of drug discovery. If the properties are weak, the candidate will have a high risk of failure or be less desirable as a drug product. This book is a tool and resource for scientists engaged in, or preparing for, the selection and optimization process. The authors describe how properties affect in vivo pharmacological activity and impact in vitro assays. Individual drug-like properties are discussed from a practical point of view, such as solubility, permeability and metabolic stability, with regard to fundamental understanding, applications of property data in drug discovery and examples of structural modifications that have achieved improved property performance. The authors also review various methods for the screening (high throughput), diagnosis (medium throughput) and in-depth (low throughput) analysis of drug properties. Serves as an essential working handbook aimed at scientists and students in medicinal chemistry Provides practical, step-by-step guidance on property fundamentals, effects, structure-property relationships, and structure modification strategies Discusses improvements in pharmacokinetics from a practical chemist's standpoint

Author : Zhengyin Yan,Gary W. Caldwell
Publisher : Springer Science & Business Media
Page : 425 pages
File Size : 54,8 Mb
Release : 2008-02-06
Category : Medical
ISBN : 9781592598007

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Optimization in Drug Discovery by Zhengyin Yan,Gary W. Caldwell Pdf

Recent analyses of drug attrition rates reveal that a significant number of drug candidates fail in the later stage of clinical development owing to absorption, distribution, metabolism, elimination (ADME), and toxicity issues. Lead optimization in drug discovery, a process attempting to uncover and correct these defects of drug candidates, is highly beneficial in lowering the cost and time to develop therapeutic drugs by reducing drug candidate failures in development. At present, parallel synthesis combining with high-throughput screening has made it easier to generate highly potent compounds (i. e. , hits). However, to be a potential drug, a hit must have drug-like characteristics in addition to potency, which include optimal physicochemical properties, reasonable ph- macokinetic parameters, and good safety profiles. Therefore, research tools must be available in drug discovery to rapidly screen for compounds with favorable drug-like properties, and thus adequate resources can be directed to projects with high potential. Optimization in Drug Discovery: In Vitro Methods is a compilation of detailed experimental protocols necessary for setting up a variety of assays important in compound evaluation. A total of 25 chapters, contributed by many experts in their research areas, cover a wide spectrum of subjects including physicochemical properties, abso- tion, plasma binding, metabolism, drug interactions, and toxicity. A good pharmacokinetic profile has long been recognized as an imp- tant drug-like characteristic. Pharmacokinetic parameters are affected by many properties of drug molecules such as physicochemical nature, abso- tion, metabolic stability, and so on.

Author : Ronald Borchardt,Edward Kerns,Michael Hageman,Dhrien Thakker,James Stevens
Publisher : Springer Science & Business Media
Page : 522 pages
File Size : 41,5 Mb
Release : 2007-12-31
Category : Medical
ISBN : 9780387449616

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Optimizing the "Drug-Like" Properties of Leads in Drug Discovery by Ronald Borchardt,Edward Kerns,Michael Hageman,Dhrien Thakker,James Stevens Pdf

This book arises from a workshop organized by the American Association of Pharmaceutical Scientists entitled "Optimizing the Drug-Like Properties of Leads in Drug Discovery," which took place in Parsippany, NJ in September 2004. The workshop focused on the optimization of the drug-like properties of leads in drug discovery. The volume outlines strategies and methodologies designed to guide pharmaceutical and biotechnology companies through the drug discovery and development process.

Author : Rajesh Krishna
Publisher : CRC Press
Page : 328 pages
File Size : 54,9 Mb
Release : 2006-05
Category : Medical
ISBN : UOM:39015064121463

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Dose Optimization in Drug Development by Rajesh Krishna Pdf

This reference provides a concise overview of the key principles in dose selection and optimization and demonstrates applicability to recent successful new drug applications. Compiling key issues and current research on safety, efficacy, and clinical pharmacology, and PK-PD, this volume critically highlights the multidisciplinary nature of drug development and spans the fields of pharmacokinetics, clinical pharmacology, biostatistics, and experimental medicine.

Author : Matthew M. Hayward
Publisher : Springer Science & Business Media
Page : 224 pages
File Size : 40,5 Mb
Release : 2010-03-12
Category : Science
ISBN : 9783642010750

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Lead-Seeking Approaches by Matthew M. Hayward Pdf

High quality leads provide the foundation for the discovery of successful clinical development candidates, and therefore the identi?cation of leads is an essential part of drug discovery. The process for the identi?cation of leads generally starts with the screening of a compound collection, either an HTS of a relatively large compound collection (hundreds of thousands to one million plus compounds) or a more focused screen of a smaller set of compounds that have been preselected for the target of interest. Virtual screening methods such as structure-based or pharmacophore-based searches can complement or replace one of the above approaches. Once hits are identi?ed from one or more of these screening methods, they need to be thoroughly characterized in order to con?rm activity and identify areas in need of optimization. Finally, once fully characterized hits are identi?ed, preliminary optimization through synthetic modi?cation is carried out to generate leads. Parallel optimization of all properties, including biological, physicochemical, and ADME is the most ef?cient approach to the identi?cation of leads. Hit characterization is described in the previous chapter. The focus of this chapter is on hit optimization and the identi?- tion of leads. After a general overview of these processes, examples taken from the literature since 2001 will be used to illustrate speci?c points. There are also a number of excellent reviews covering the lead identi?cation process [1–6].

Author : Klara Valko
Publisher : John Wiley & Sons
Page : 354 pages
File Size : 46,7 Mb
Release : 2013-11-25
Category : Medical
ISBN : 9781118770320

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Physicochemical and Biomimetic Properties in Drug Discovery by Klara Valko Pdf

Demonstrating how and why to measure physicochemical and biomimetic properties in early stages of drug discovery for lead optimization, Physicochemical and Biomimetic Properties in Drug Discovery encourages readers to discover relationships between various measurements and develop a sense of interdisciplinary thinking that will add to new research in drug discovery. This practical guide includes detailed descriptions of state-of-the-art chromatographic techniques and uses real-life examples and models to help medicinal chemists and scientists and advanced graduate students apply measurement data for optimal drug discovery.

Author : Puratchikody, A.,Prabu, S. Lakshmana,Umamaheswari, A.
Publisher : IGI Global
Page : 332 pages
File Size : 46,5 Mb
Release : 2018-11-23
Category : Medical
ISBN : 9781522573272

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Computer Applications in Drug Discovery and Development by Puratchikody, A.,Prabu, S. Lakshmana,Umamaheswari, A. Pdf

With more restrictions upon animal experimentations, pharmaceutical industries are currently focusing on a new generation of experiments and technologies that are considerably more efficient and less controversial. The integration of computational and experimental strategies has led to the identification and development of promising compounds. Computer Applications in Drug Discovery and Development is a pivotal reference source that provides innovative research on the application of computers for discovering and designing new drugs in modern molecular biology and medicinal chemistry. While highlighting topics such as chemical structure databases and dataset utilization, this publication delves into the current panorama of drug discovery, where high drug failure rates are a major concern and properly designed virtual screening strategies can be a time-saving, cost-effective, and productive alternative. This book is ideally designed for chemical engineers, pharmacists, molecular biologists, students, researchers, and academicians seeking current research on the unexplored avenues and future perspectives of drug design.

Author : Zoran Antonijevic
Publisher : Springer
Page : 202 pages
File Size : 46,7 Mb
Release : 2014-10-10
Category : Business & Economics
ISBN : 9783319090757

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Optimization of Pharmaceutical R&D Programs and Portfolios by Zoran Antonijevic Pdf

Very little has been published on optimization of pharmaceutical portfolios. Moreover, most of published literature is coming from the commercial side, where probability of technical success (PoS) is treated as fixed, and not as a consequence of development strategy or design. In this book there is a strong focus on impact of study design on PoS and ultimately on the value of portfolio. Design options that are discussed in different chapters are dose-selection strategies, adaptive design and enrichment. Some development strategies that are discussed are indication sequencing, optimal number of programs and optimal decision criteria. This book includes chapters written by authors with very broad backgrounds including financial, clinical, statistical, decision sciences, commercial and regulatory. Many authors have long held executive positions and have been involved with decision making at a product or at a portfolio level. As such, it is expected that this book will attract a very broad audience, including decision makers in pharmaceutical R&D, commercial and financial departments. The intended audience also includes portfolio planners and managers, statisticians, decision scientists and clinicians. Early chapters describe approaches to portfolio optimization from big Pharma and Venture Capital standpoints. They have stronger focus on finances and processes. Later chapters present selected statistical and decision analysis methods for optimizing drug development programs and portfolios. Some methodological chapters are technical; however, with a few exceptions they require a relatively basic knowledge of statistics by a reader.

Author : Florencio Zaragoza Dörwald
Publisher : John Wiley & Sons
Page : 627 pages
File Size : 43,5 Mb
Release : 2013-02-04
Category : Science
ISBN : 9783527645657

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Lead Optimization for Medicinal Chemists by Florencio Zaragoza Dörwald Pdf

Small structural modifications can significantly affect the pharmacokinetic properties of drug candidates. This book, written by a medicinal chemist for medicinal chemists, is a comprehensive guide to the pharmacokinetic impact of functional groups, the pharmacokinetic optimization of drug leads, and an exhaustive collection of pharmacokinetic data, arranged according to the structure of the drug, not its target or indication. The historical origins of most drug classes and general aspects of modern drug discovery and development are also discussed. The index contains all the drug names and synonyms to facilitate the location of any drug or functional group in the book. This compact working guide provides a wealth of information on the ways small structural modifications affect the pharmacokinetic properties of organic compounds, and offers plentiful, fact-based inspiration for the development of new drugs. This book is mainly aimed at medicinal chemists, but may also be of interest to graduate students in chemical or pharmaceutical sciences, preparing themselves for a job in the pharmaceutical industry, and to healthcare professionals in need of pharmacokinetic data.

Author : Institute of Medicine,Board on Health Sciences Policy,Forum on Neuroscience and Nervous System Disorders
Publisher : National Academies Press
Page : 107 pages
File Size : 50,5 Mb
Release : 2014-02-06
Category : Medical
ISBN : 9780309292498

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Improving and Accelerating Therapeutic Development for Nervous System Disorders by Institute of Medicine,Board on Health Sciences Policy,Forum on Neuroscience and Nervous System Disorders Pdf

Improving and Accelerating Therapeutic Development for Nervous System Disorders is the summary of a workshop convened by the IOM Forum on Neuroscience and Nervous System Disorders to examine opportunities to accelerate early phases of drug development for nervous system drug discovery. Workshop participants discussed challenges in neuroscience research for enabling faster entry of potential treatments into first-in-human trials, explored how new and emerging tools and technologies may improve the efficiency of research, and considered mechanisms to facilitate a more effective and efficient development pipeline. There are several challenges to the current drug development pipeline for nervous system disorders. The fundamental etiology and pathophysiology of many nervous system disorders are unknown and the brain is inaccessible to study, making it difficult to develop accurate models. Patient heterogeneity is high, disease pathology can occur years to decades before becoming clinically apparent, and diagnostic and treatment biomarkers are lacking. In addition, the lack of validated targets, limitations related to the predictive validity of animal models - the extent to which the model predicts clinical efficacy - and regulatory barriers can also impede translation and drug development for nervous system disorders. Improving and Accelerating Therapeutic Development for Nervous System Disorders identifies avenues for moving directly from cellular models to human trials, minimizing the need for animal models to test efficacy, and discusses the potential benefits and risks of such an approach. This report is a timely discussion of opportunities to improve early drug development with a focus toward preclinical trials.