Book
1 online resource.
  • Aims and Objectives
  • Materials and Methods
  • Development and Validation of High-Throughput Crystallisation and Analysis (HTCAA) Methodology for Physical Form Screening
  • Predicting Crystallisability of Organic Molecules Using Statistical Modelling Techniques
  • Exploring the Crystal Structure Landscape of Olanzapine
  • Exploring the Physical Form Landscape of Clozapine, Amoxapine and Loxapine
  • Conclusions and Further Work.
This thesis investigates a range of experimental and computational approaches to the discovery of solid forms. It illustrates an inexpensive, practical and accurate way to predict the crystallizability of organic compounds based on molecular structure alone, while also highlighting the molecular factors that inhibit or promote crystallization. Furthermore, readers will gain a better understanding of the key factors underpinning solid-state structure and diversity. A major part of the thesis highlights experimental work carried out on two structurally very similar compounds, while another main section examines the influence of small changes in structure and substituents on solid-state structure and diversity using computational tools including crystal structure prediction, PIXEL calculations, Xpac, Mercury and statistical modelling tools. In closing, the author presents a fast validated method for solid-state form screening using Raman microscopy on multi-well plates to explore the experimental crystallization space.
Book
1 online resource (580 pages).
  • Front Cover; Drug-Like Properties: Concepts, Structure, Design, and Methods from ADME to Toxicity Optimization; Copyright; Dedication; Contents; Preface; Preface to Second Edition; Preface to First Edition; Chapter 1: Introduction; 1.1. Drug-like Properties in Drug Discovery; 1.2. Purpose of This Book; Problems; References; Chapter 2: Benefits of Property Assessment and Good Drug-Like Properties; 2.1. Introduction; 2.2. Discovery Scientists Optimize Many Properties; 2.3. Introduction to the Drug Discovery and Development Process; 2.4. Benefits of Good Drug-like Properties
  • 2.4.1. Reduced Development Attrition2.4.2. More Efficient Drug Discovery; 2.4.3. More Efficient Drug Development; 2.4.4. Higher Patient Compliance; 2.4.5. Improved Biological Research in Drug Discovery; 2.4.6. Enabled Partnerships for Drug Development; 2.4.7. Human Modeling and Clinical Planning; 2.4.8. Balance of Properties and Activity; 2.5. Property Profiling in Drug Discovery; 2.6. Drug-like Property Optimization in Drug Discovery; Problems; References; Chapter 3: In Vivo Environments Affect Drug Exposure; 3.1. Introduction; 3.2. Drug Dosing; 3.3. Stomach
  • 3.3.1. Gastric Acidic Degradation3.4. Intestinal Environment; 3.4.1. Dissolution Rate; 3.4.2. Solubility; 3.4.3. Permeability; 3.4.4. Intestinal Metabolism; 3.4.5. Intestinal Enzymatic Hydrolysis; 3.4.6. Absorption Enhancement in the Intestine; 3.5. Bloodstream; 3.5.1. Plasma Enzyme Hydrolysis; 3.5.2. Plasma Protein Binding; 3.5.3. Red Blood Cell Binding; 3.6. Liver; 3.6.1. Permeation into and out of Hepatocytes; 3.6.2. Hepatic Metabolism; 3.6.3. Biliary Extraction; 3.7. Kidney; 3.8. Blood-Tissue Barriers; 3.9. Tissue Distribution; 3.9.1. Nonspecific Binding in Tissue
  • 3.10. Consequences of Chirality3.11. Overview of in vivo Challenges to Drug Exposure; Problems; References; Chapter 4: Prediction Rules for Rapid Property Profiling from Structure; 4.1. Introduction; 4.2. General Concepts for Prediction Rules; 4.3. Rule of 5; 4.4. Veber Rules; 4.5. Waring Rules; 4.6. Golden Triangle; 4.7. Other Predictive Rules; 4.8. Application of Rules for Compound Assessment; 4.9. Applications of Predictive Rules; Problems; References; Chapter 5: Lipophilicity; 5.1. Lipophilicity Fundamentals; 5.2. Lipophilicity Effects
  • 5.3. Lipophilicity Case Studies and Structure Modification5.3.1. Lipophilicity Modification for Biological Activity; 5.3.2. Lipophilicity Modification for Pharmacokinetics; 5.3.3. Lipophilicity Modification for Toxicity; Problems; References; Chapter 6: pKa; 6.1. pKa Fundamentals; 6.2. pKa Effects; 6.2.1. pKa Affects Efficacy; 6.2.2. pKa Affects Pharmacokinetics; 6.2.3. pKa Affects Toxicity; 6.3. pKa Case Studies; 6.3.1. pKa and Activity Examples; 6.3.2. pKa and Pharmacokinetics Examples; 6.4. Structure Modification Strategies for pKa; Problems; References; Chapter 7: Solubility
Of the thousands of novel compounds that a drug discovery project team invents and that bind to the therapeutic target, only a fraction have sufficient ADME (absorption, distribution, metabolism, elimination) properties, and acceptable toxicology properties, to become a drug product that will successfully complete human Phase I clinical trials. Drug-Like Properties: Concepts, Structure Design and Methods from ADME to Toxicity Optimization, Second Edition, provides scientists and students the background and tools to understand, discover, and develop optimal clinical candidates. This valuable resource explores physiochemical properties, including solubility and permeability, before exploring how compounds are absorbed, distributed, and metabolized safely and stably. Review chapters provide context and underscore the importance of key concepts such as pharmacokinetics, toxicity, the blood-brain barrier, diagnosing drug limitations, prodrugs, and formulation. Building on those foundations, this thoroughly updated revision covers a wide variety of current methods for the screening (high throughput), diagnosis (medium throughput) and in-depth (low throughput) analysis of drug properties for process and product improvement. From conducting key assays for interpretation and structural analysis, the reader learns to implement modification methods and improve each ADME property. Through valuable case studies, structure-property relationship descriptions, and structure modification strategies, Drug-Like Properties, Second Edition, offers tools and methods for ADME/Tox scientists through all aspects of drug research, discovery, design, development, and optimization.
Book
xi, 220 pages : illustrations ; 24 cm.
Chemistry & ChemEng Library (Swain)
Book
xv, 341 pages : illustrations ; 26 cm.
  • Preface xi Contributors xiii PART I. INFECTIOUS DISEASES 1 Chapter 1. Entecavir (Baraclude): A Carbocyclic Nucleoside for the Treatment of Chronic Hepatitis B 3 1 Background 3 2 Pharmacology 5 3 Structure Activity Relationship (SAR) 6 4 Pharmacokinetics and Drug Metabolism 7 5 Efficacy and Safety 8 6 Syntheses 8 7 References 14 Chapter 2. Telaprevir (Incivek) and Boceprevir (Victrelis): NS3/4A Inhibitors for Treatment for Hepatitis C Virus (HCV) 15 1 Background 16 2 Pharmacology 16 3 Structure Activity Relationship (SAR) 17 4 PK and Drug Metabolism 20 5 Efficacy and Safety 22 6 Synthesis 24 7 Conclusions 38 8 References 39 Chapter 3. Daclatasvir (Daklinza): The First-in-Class HCV NS5A Replication Complex Inhibitor 43 1 Background 43 2 Discovery Medicinal Chemistry 45 3 Mode of Action 48 4 Pharmacokinetics and Drug Metabolism 49 5 Efficacy and Safety 49 6 Syntheses 52 7 References 57 Chapter 4. Sofosbuvir (Sovaldi): The First-in-Class HCV NS5B Nucleotide Polymerase Inhibitor 61 1 Background 61 2 Pharmacology 63 3 Structure Activity Relationship (SAR) 64 4 Pharmacokinetics and Drug Metabolism 68 5 Efficacy and Safety 69 6 Syntheses 72 7 Summary 76 8 References 76 Chapter 5. Bedaquiline (Sirturo): A Diarylquinoline that Blocks Tuberculosis ATP Synthase for the Treatment of Multi-Drug Resistant Tuberculosis 81 1 Background 81 2 Pharmacology 84 3 Structure Activity Relationship (SAR) 85 4 Pharmacokinetics and Drug Metabolism 86 5 Efficacy and Safety 87 6 Syntheses 88 7 References 96 PART II. CANCER 99 Chapter 6. Enzalutamide (Xtandi): An Androgen Receptor Antagonist for Late-Stage Prostate Cancer 101 1 Background 101 2 Pharmacology 103 3 Structure Activity Relationship (SAR) 104 4 Pharmacokinetics and Drug Metabolism 108 5 Efficacy and Safety 109 6 Synthesis 111 7 Compounds in Development 114 8 References 115 Chapter 7. Crizotinib (Xalkori): The First-in-Class ALK/ROS Inhibitor for Non-small Cell Lung Cancer 119 1 Background: Non-small Cell Lung Cancer (NSCLC) Treatment 119 2 Discovery Medicinal Chemistry Effort: SAR and Lead Optimization of Compound 2 as a c-Met Inhibitor 120 3 ALK and ROS in Non-small Cell Lung Cancer (NSCLC) Treatment 127 4 Preclinical Model Tumor Growth Inhibition Efficacy and Pharmacology 127 5 Human Clinical Trials 128 6 Introduction to the Synthesis and Limitations of the Discovery Route to Crizotinib Analogs 129 7 Process Chemistry: Initial Improvements 131 8 Process Chemistry: Enabling Route to Crizotinib 135 9 Development of the Commercial Process 141 10 Commercial Synthesis of Crizotinib 147 11 References 152 Chapter 8. Ibrutinib (Imbruvica): The First-in-Class Btk Inhibitor for Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia, and Waldenstrom's Macroglobulinemia 157 1 Background 157 2 Pharmacology 159 3 Structure Activity Relationship (SAR) 159 4 Pharmacokinetics and Drug Metabolism 161 5 Efficacy and Safety 161 6 Syntheses 162 7 References 164 Chapter 9. Palbociclib (Ibrance): The First-in-Class CDK4/6 Inhibitor for Breast Cancer 167 1 Background 167 2 Pharmacology 168 3 Discovery Program 169 4 Preclinical Profile of Palbociclib 175 5 Clinical Profile of Palbociclib 176 6 Early Process Development for Palbociclib 177 7 Commercial Process for Preparation of Palbociclib 192 8 References 193 PART III. CARDIOVASCULAR DISEASES 197 Chapter 10. Ticagrelor (Brilinta) and Dabigatran Etexilate (Pradaxa): P2Y12 Platelet Inhibitors as Anti-coagulants 199 1 Introduction 200 2 Dabigatran Etexilate 200 3 Ticagrelor 207 4 The Future 219 5 References 220 PART IV. CNS DRUGS 223 Chapter 11. Suvorexant (BELSOMRA): The First-in-Class Orexin Antagonist for Insomnia 225 1 Background 225 2 Pharmacology 229 3 Pharmacokinetics and Drug Metabolism 230 4 Efficacy and Safety 231 5 Structure Activity Relationship (SAR) 231 6 Synthesis 233 7 References 239 Chapter 12. Lorcaserin (Belviq): Serotonin 2C Receptor Agonist for the Treatment of Obesity 243 1 Background 243 2 Pharmacology 245 3 Structure Activity Relationship (SAR) 246 4 Pharmacokinetics and Drug Metabolism 248 5 Efficacy and Safety 249 6 Synthesis 250 7 References 253 Chapter 13. Fingolimod (Gilenya): The First Oral Treatment for Multiple Sclerosis 255 1 Background 255 2 Structure Activity Relationship (SAR) 257 3 Pharmacology 259 4 Human Pharmacokinetics and Drug Metabolism 260 5 Efficacy and Safety 261 6 Syntheses 263 7 Summary 268 8 References 269 Chapter 14. Perampanel (Fycompa): AMPA Receptor Antagonist for the Treatment of Seizure 271 1 Background 271 2 Pharmacology 273 3 Structure Activity Relationship (SAR) 274 4 Pharmacokinetics and Drug Metabolism 276 5 Efficacy and Safety 277 6 Syntheses 278 7 References 280 PART V. ANTI-INFLAMMATORY DRUGS 283 Chapter 15. Tofacitinib (Xeljanz): The First-in-Class JAK Inhibitor for the Treatment of Rheumatoid Arthritis 285 1 Background 285 2 Structure Activity Relationships (SAR) 287 3 Safety, Pharmacology and Pharmacokinetics 289 4 Syntheses 290 5 Development of the Commercial Manufacturing Process 292 6 References 300 PART VI. MISCELLANEOUS DRUGS 303 Chapter 16. Ivacaftor (Kalydeco): A CFTR Potentiator for the Treatment of Cystic Fibrosis 305 1 Background 305 2 Pharmacology 306 3 Structure Activity Relationship (SAR) 307 4 Pharmacokinetics and Drug Metabolism 308 5 Efficacy and Safety 310 6 Syntheses 311 7 References 315 Chapter 17. Febuxostat (Uloric): A Xanthine Oxidase Inhibitor for the Treatment of Gout 317 1 Background 317 2 Pharmacology 319 3 Structure Activity Relationship (SAR) 320 4 Pharmacokinetics and Drug Metabolism 321 5 Efficacy and Safety 322 6 Syntheses 323 7 Drug in Development: Lesinurad Sodium 328 8 References 330 Index 331.
  • (source: Nielsen Book Data)
This book covers all aspects of the medicinal chemistry of the latest drugs, and the cutting-edge science associated with them. Following the editors 3 successful drug synthesis books, this provides expert analysis of the pros and cons of different synthetic routes and demystifies the process of modern drug discovery for practitioners and researchers. * Summarizes for each drug: respective disease area, important properties and SAR (structure-activity relationship), and chemical synthesis routes / options * Includes case studies in each chapter * Illustrates how chemistry, biology, pharmacokinetics, and a host of disciplines come together to produce successful medicines * Explains the advantages of process synthesis versus the synthetic route for drug discovery.
(source: Nielsen Book Data)
Chemistry & ChemEng Library (Swain)
Book
1 online resource.
Initial proposal summary: The evolution of antibiotic-resistant mutants among bacteria (superbugs) is a persistent and growing threat to public health. In many ways, we are engaged in a war with these microorganisms, where the corresponding arms race involves chemical weapons and biological targets. Just as advances in microelectronics, imaging technology and feature recognition software have turned conventional munitions into smart bombs, the long-term objectives of this proposal are to develop highly effective antibiotics using next-generation biomolecular modeling capabilities in tandem with novel subatomic feature detection software. Using model compounds and targets, our design methodology will be validated with correspondingly ultra-high resolution structure-determination methods at premier DOE facilities (single-crystal X-ray diffraction at Argonne National Laboratory, and neutron diffraction at Oak Ridge National Laboratory). The objectives and accomplishments are summarized.
Book
online resource (xi, 338 pages) : illustrations ; 26 cm
  • De novo peptide structure prediction : an overview / Pierre Thévenet [and three others]
  • Molecular modeling of peptides / Krzysztof Kuczera
  • Improved methods for classification, prediction, and design of antimicrobial peptides / Guangshun Wang
  • Building MHC class II epitope predictor using machine learning approaches / Loan Ping Eng, Tin Wee Tan, and Joo Chuan Tong
  • Brownian dynamics simulation of peptides with the University of Houston Brownian Dynamics (UHBD) program / Tongye Shen and Chung F. Wong
  • Computational prediction of short linear motifs from protein sequences / Richard J. Edwards and Nicolas Palopoli
  • Peptide toxicity prediction / Sudheer Gupta [and five others]
  • Synthetic and structural routes for the rational conversion of peptides into small molecules / Pasqualina Liana Scognamiglio, Giancarlo Morelli, and Daniela Marasco
  • In silico design of antimicrobial peptides / Giuseppe Maccari, Mariagrazia Di Luca, and Riccardo Nifosì
  • Information-driven modeling of protein-peptide complexes / Mikael Trellet, Adrien S.J. Melquiond, and Alexandre M.J.J. Bonvin
  • Computational approaches to developing short cyclic peptide modulators of protein-protein interactions / Fergal J. Duffy, Marc Devocelle, and Denis C. Shields
  • A use of homology modeling and molecular docking methods : to explore binding mechanisms of nonylphenol and bisphenol A with antioxidant enzymes / Mannu Jayakanthan [and three others]
  • Computational peptide vaccinology / Johannes Söllner
  • Computational modeling of peptide-aptamer binding / Kristen L. Rhinehardt, Ram V. Mohan, and Goundla Srinivas.
Medical Library (Lane)
Book
1 online resource.
  • Chapter 1. Introduction of computational pharmaceutics Defang Ouyang Chapter 2. Crystal energy landscapes for aiding crystal form selection Sarah Price Chapter 3. Solubilization of poor-soluble drugs in cyclodextron formulation Defang Ouyang Chapter 4. Molecular Modeling for Polymeric and Micellar Drug Delivery Sharon M. Loverde Chapter 5. Solid dispersion - a pragmatic method to improve the bioavailability of poorly soluble drugs Defang Ouyang Chapter 6. Computer simulations of lipid membranes and liposomes for drug delivery Becky Notman Chapter 7. Molecular modeling for protein aggregation and formulation Jim Warwicker Chapter 8. Computational simulation of drug delivery by nano-materials at molecular level Youyong Li Chapter 9. Molecular and analytical modeling of nanodiamond for drug delivery applications Amanda Barnard Chapter 10. Molecular modeling of LDH drug delivery systems Vinuthaa Murthy Chapter 11. Molecular dynamics simulation as a tool to study the efficacy of PEGylation Alex Bunker Chapter 12. Synchrotron Radiation Micro Computed Tomography: a new approach for quantitative 3D structural architecture of drug delivery systems Jiwen Zhang Chapter 13. Pharmacokinetic modelling and simulation in drug delivery Raj Index.
  • (source: Nielsen Book Data)
Molecular modeling techniques have been widely used in drug discovery fields for rational drug design and compound screening. Now these techniques are used to model or mimic the behavior of molecules, and help us study formulation at the molecular level. Computational pharmaceutics enables us to understand the mechanism of drug delivery, and to develop new drug delivery systems. The book discusses the modeling of different drug delivery systems, including cyclodextrins, solid dispersions, polymorphism prediction, dendrimer-based delivery systems, surfactant-based micelle, polymeric drug delivery systems, liposome, protein/peptide formulations, non-viral gene delivery systems, drug-protein binding, silica nanoparticles, carbon nanotube-based drug delivery systems, diamond nanoparticles and layered double hydroxides (LDHs) drug delivery systems. Although there are a number of existing books about rational drug design with molecular modeling techniques, these techniques still look mysterious and daunting for pharmaceutical scientists. This book fills the gap between pharmaceutics and molecular modeling, and presents a systematic and overall introduction to computational pharmaceutics. It covers all introductory, advanced and specialist levels. It provides a totally different perspective to pharmaceutical scientists, and will greatly facilitate the development of pharmaceutics. It also helps computational chemists to look for the important questions in the drug delivery field. This book is included in the Advances in Pharmaceutical Technology book series.
(source: Nielsen Book Data)
Book
1 online resource.
  • Different flavours of Fragments-- Advances in SPR Technology-- Applications of NMR in Fragment-Based Drug Discovery-- Issues around Fragments as an Approach, including a Computational/in silico Perspectives on Fragment-Based Drug Discovery-- Fragment-Based Drug Discovery of Kinase Inhibitors-- Fragment-Based Discovery of Antibacterials-- Strategies for Fragment-Based Lead Generation-- Fragment-Based Approaches to Epigenetic Targets-- Application of Fragment-Based Drug Discovery to GPCRs-- Fragment-Based Drug Discovery applied to Protein-Protein Interactions-- Probing Difficult Targets.
  • (source: Nielsen Book Data)
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.
(source: Nielsen Book Data)
Book
ix, 230 pages : illustrations (some color) ; 27 cm.
  • Solvation methods for protein-ligand docking / Rachelle J. Bienstock
  • Binding site druggability assessment in fragment-based drug design / Yu Zhou and Niu Huang
  • Generating "fragment-based virtual library" using pocket similarity search of ligand-receptor complexes / Raed S. Khashan
  • Virtual fragment preparation for computational fragment- based drug design / Jennifer L. Ludington
  • Fragment library design : using cheminformatics and expert chemists to fill gaps in existing fragment libraries / Peter S. Kutchukian ... [et al.]
  • Protocol for fragment hopping / Kevin B. Teuscher and Haitao Ji
  • Site identification by ligand competitive saturation (SILCS) simulations for fragment-based drug Design / Christina E. Faller ... [et al.]
  • Computational fragment-based de novo design protocol guided by ligand efficiency indices (LEI) / Álvaro Cortés-Cabrera, Federico Gago, and Antonio Morreale
  • Scoring functions for fragment-based drug discovery / Jui-Chih Wang and Jung-Hsin Lin
  • Computational methods for fragment-based ligand design : growing and linking / Rachelle J. Bienstock
  • Design strategies for computational fragment-based drug design / Zenon D. Konteatis
  • Protein binding site analysis for drug discovery using a computational fragment-based method / Jennifer L. Ludington
  • Fragment-based design of kinase inhibitors : a practical guide / Jon A. Erickson
  • Designing a small molecule erythropoietin mimetic / Frank Guarnieri
  • Designing an orally available nontoxic p38 inhibitor with a fragment-based strategy / Frank Guarnieri.
This volume covers the techniques necessary for a successful fragment-based drug design project, beginning from defining the problem in terms of preparing the protein model, identifying potential binding sites, and the consideration of various candidate fragments for simulation. The second part discusses the technical aspects that various methods have used to simulate fragment binding to a target protein by using Monte Carlo, molecular dynamics, and docking algorithms. After simulations, fragments are assembled into molecules using a variety of approaches, which are explored next. A discussion of design strategies and consideration of drug-like properties is included as part of the design process at this stage. Finally, several examples of successful fragment-based drug design projects are presented. Written for the Methods in Molecular Biology series, this work contains the kind of detailed description and implementation advice to encourage success in the lab. Practical and cutting-edge, Fragment-Based Methods in Drug Discovery takes into account the great accomplishments in the field to provide an ideal guide for researchers continuing to investigate this exciting area of pharmacological study.
(source: Nielsen Book Data)
Biology Library (Falconer)
Book
online resource (ix, 230 pages) : illustrations (some color) ; 27 cm
  • Solvation methods for protein-ligand docking / Rachelle J. Bienstock
  • Binding site druggability assessment in fragment-based drug design / Yu Zhou and Niu Huang
  • Generating "fragment-based virtual library" using pocket similarity search of ligand-receptor complexes / Raed S. Khashan
  • Virtual fragment preparation for computational fragment- based drug design / Jennifer L. Ludington
  • Fragment library design : using cheminformatics and expert chemists to fill gaps in existing fragment libraries / Peter S. Kutchukian ... [et al.]
  • Protocol for fragment hopping / Kevin B. Teuscher and Haitao Ji
  • Site identification by ligand competitive saturation (SILCS) simulations for fragment-based drug Design / Christina E. Faller ... [et al.]
  • Computational fragment-based de novo design protocol guided by ligand efficiency indices (LEI) / Álvaro Cortés-Cabrera, Federico Gago, and Antonio Morreale
  • Scoring functions for fragment-based drug discovery / Jui-Chih Wang and Jung-Hsin Lin
  • Computational methods for fragment-based ligand design : growing and linking / Rachelle J. Bienstock
  • Design strategies for computational fragment-based drug design / Zenon D. Konteatis
  • Protein binding site analysis for drug discovery using a computational fragment-based method / Jennifer L. Ludington
  • Fragment-based design of kinase inhibitors : a practical guide / Jon A. Erickson
  • Designing a small molecule erythropoietin mimetic / Frank Guarnieri
  • Designing an orally available nontoxic p38 inhibitor with a fragment-based strategy / Frank Guarnieri.
Medical Library (Lane)
Book
1 online resource.
  • PREFACE xvii CONTRIBUTORS xix 1 Introduction 1 Steven A. Haney 1.1 The Beginning of High Content Screening, 1 1.2 Six Skill Sets Essential for Running HCS Experiments, 4 1.3 Integrating Skill Sets into a Team, 7 1.4 A Few Words on Experimental Design, 8 1.5 Conclusions, 9 Key Points, 9 Further Reading, 10 References, 10 SECTION I FIRST PRINCIPLES 11 2 Fluorescence and Cell Labeling 13 Anthony Davies and Steven A. Haney 2.1 Introduction, 13 2.2 Anatomy of Fluorescent Probes, Labels, and Dyes, 14 2.3 Stokes Shift and Biological Fluorophores, 15 2.4 Fluorophore Properties, 16 2.5 Localization of Fluorophores Within Cells, 18 2.6 Multiplexing Fluorescent Reagents, 26 2.7 Specialized Imaging Applications Derived from Complex Properties of Fluorescence, 27 2.8 Conclusions, 30 Key Points, 31 Further Reading, 31 References, 31 3 Microscopy Fundamentals 33 Steven A. Haney, Anthony Davies, and Douglas Bowman 3.1 Introducing HCS Hardware, 33 3.2 Deconstructing Light Microscopy, 37 3.3 Using the Imager to Collect Data, 43 3.4 Conclusions, 45 Key Points, 45 Further Reading, 46 References, 46 4 Image Processing 47 John Bradley, Douglas Bowman, and Arijit Chakravarty 4.1 Overview of Image Processing and Image Analysis in HCS, 47 4.2 What is a Digital Image?, 48 4.3 Addressing Pixel Values in Image Analysis Algorithms, 48 4.4 Image Analysis Workflow, 49 4.5 Conclusions, 60 Key Points, 60 Further Reading, 60 References, 60 SECTION II GETTING STARTED 63 5 A General Guide to Selecting and Setting Up a High Content Imaging Platform 65 Craig Furman, Douglas Bowman, Anthony Davies, Caroline Shamu, and Steven A. Haney 5.1 Determining Expectations of the HCS System, 65 5.2 Establishing an HC Platform Acquisition Team, 66 5.3 Basic Hardware Decisions, 67 5.4 Data Generation, Analysis, and Retention, 72 5.5 Installation, 73 5.6 Managing the System, 75 5.7 Setting Up Workflows for Researchers, 77 5.8 Conclusions, 78 Key Points, 79 Further Reading, 79 6 Informatics Considerations 81 Jay Copeland and Caroline Shamu 6.1 Informatics Infrastructure for High Content Screening, 81 6.2 Using Databases to Store HCS Data, 86 6.3 Mechanics of an Informatics Solution, 89 6.4 Developing Image Analysis Pipelines: Data Management Considerations, 95 6.5 Compliance With Emerging Data Standards, 99 6.6 Conclusions, 101 Key Points, 102 Further Reading, 102 References, 102 7 Basic High Content Assay Development 103 Steven A. Haney and Douglas Bowman 7.1 Introduction, 103 7.2 Initial Technical Considerations for Developing a High Content Assay, 103 7.3 A Simple Protocol to Fix and Stain Cells, 107 7.4 Image Capture and Examining Images, 109 7.5 Conclusions, 111 Key Points, 112 Further Reading, 112 Reference, 112 SECTION III ANALYZING DATA 113 8 Designing Metrics for High Content Assays 115 Arijit Chakravarty, Steven A. Haney, and Douglas Bowman 8.1 Introduction: Features, Metrics, Results, 115 8.2 Looking at Features, 116 8.3 Metrics and Results: The Metric is the Message, 120 8.4 Types of High Content Assays and Their Metrics, 121 8.5 Metrics to Results: Putting it all Together, 126 8.6 Conclusions, 128 Key Points, 128 Further Reading, 129 References, 129 9 Analyzing Well-Level Data 131 Steven A. Haney 9.1 Introduction, 131 9.2 Reviewing Data, 132 9.3 Plate and Control Normalizations of Data, 134 9.4 Calculation of Assay Statistics, 135 9.5 Data Analysis: Hit Selection, 138 9.6 IC 50 Determinations, 139 9.7 Conclusions, 143 Key Points, 143 Further Reading, 143 References, 144 10 Analyzing Cell-Level Data 145 Steven A. Haney, Lin Guey, and Arijit Chakravarty 10.1 Introduction, 145 10.2 Understanding General Statistical Terms and Concepts, 146 10.3 Examining Data, 149 10.4 Developing a Data Analysis Plan, 155 10.5 Cell-Level Data Analysis: Comparing Distributions Through Inferential Statistics, 158 10.6 Analyzing Normal (or Transformed) Data, 159 10.7 Analyzing Non-Normal Data, 160 10.8 When to Call For Help, 162 10.9 Conclusions, 162 Key Points, 162 Further Reading, 163 References, 163 SECTION IV ADVANCED WORK 165 11 Designing Robust Assays 167 Arijit Chakravarty, Douglas Bowman, Anthony Davies, Steven A. Haney, and Caroline Shamu 11.1 Introduction, 167 11.2 Common Technical Issues in High Content Assays, 167 11.3 Designing Assays to Minimize Trouble, 172 11.4 Looking for Trouble: Building in Quality Control, 177 11.5 Conclusions, 179 Key Points, 180 Further Reading, 180 References, 180 12 Automation and Screening 181 John Donovan, Arijit Chakravarty, Anthony Davies, Steven A. Haney, Douglas Bowman, John Ringeling, and Ben Knight 12.1 Introduction, 181 12.2 Some Preliminary Considerations, 181 12.3 Laboratory Options, 183 12.4 The Automated HCS Laboratory, 186 12.5 Conclusions, 192 Key Points, 192 Further Reading, 193 13 High Content Analysis for Tissue Samples 195 Kristine Burke, Vaishali Shinde, Alice McDonald, Douglas Bowman, and Arijit Chakravarty 13.1 Introduction, 195 13.2 Design Choices in Setting Up a High Content Assay in Tissue, 196 13.3 System Configuration: Aspects Unique to Tissue-Based HCS, 199 13.4 Data Analysis, 203 13.5 Conclusions, 207 Key Points, 207 Further Reading, 207 References, 208 SECTION V HIGH CONTENT ANALYTICS 209 14 Factoring and Clustering High Content Data 211 Steven A. Haney 14.1 Introduction, 211 14.2 Common Unsupervised Learning Methods, 212 14.3 Preparing for an Unsupervised Learning Study, 218 14.4 Conclusions, 228 Key Points, 228 Further Reading, 228 References, 229 15 Supervised Machine Learning 231 Jeff Palmer and Arijit Chakravarty 15.1 Introduction, 231 15.2 Foundational Concepts, 232 15.3 Choosing a Machine Learning Algorithm, 234 15.4 When Do You Need Machine Learning, and How Do You Use IT?, 243 15.5 Conclusions, 244 Key Points, 244 Further Reading, 244 Appendix A Websites and Additional Information on Instruments, Reagents, and Instruction 247 Appendix B A Few Words About One Letter: Using R to Quickly Analyze HCS Data 249 Steven A. Haney B.1 Introduction, 249 B.2 Setting Up R, 250 B.3 Analyzing Data in R, 253 B.4 Where to Go Next, 261 Further Reading, 263 Appendix C Hypothesis Testing for High Content Data: A Refresher 265 Lin Guey and Arijit Chakravarty C.1 Introduction, 265 C.2 Defining Simple Hypothesis Testing, 266 C.3 Simple Statistical Tests to Compare Two Groups, 269 C.4 Statistical Tests on Groups of Samples, 276 C.5 Introduction to Regression Models, 280 C.6 Conclusions, 285 Key Concepts, 286 Further Reading, 286 GLOSSARY 287 TUTORIAL 295 INDEX 323.
  • (source: Nielsen Book Data)
Using a collaborative and interdisciplinary author base with experience in the pharmaceutical industry and academia, this book is a practical resource for high content (HC) techniques. Instructs readers on the fundamentals of high content screening (HCS) techniques Focuses on practical and widely-used techniques like image processing and multiparametric assays Breaks down HCS into individual modules for training and connects them at the end Includes a tutorial chapter that works through sample HCS assays, glossary, and detailed appendices.
(source: Nielsen Book Data)
Book
online resource (xx, 327 pages) : illustrations
  • Introduction / Steven Haney
  • Fluorescence and cell labeling / Anthony Davies, Steven Haney
  • Microscopy fundamentals / Steven Haney, Anthony Davies, Doug Bowman
  • Image processing / John Bradley, Doug Bowman, Arijit Chakravarty
  • Selecting and setting up a high content imaging platform / Craig Furman, Doug Bowman, Anthony Davies, Caroline Shamu, Steven Haney
  • Informatics considerations / Jay Copeland, Caroline Shamu
  • Basic high content assay development / Steven Haney, Doug Bowman
  • Designing metrics for high content assays / Arijit Chakravarty, Steven Haney, Doug Bowman
  • Analyzing well-level data / Steven Haney, Arijit Chakravarty
  • Analyzing cell level data / Steven Haney, Lin Guey, Arijit Chakravarty
  • Designing robust assays / Arijit Chakrivarty, Doug Bowman, Anthony Davies, Caroline Shamu
  • Automation and screening / John Donovan, Arijit Chakravarty, Anthony Davies, Steven Haney, Doug Bowman, John Ringling, Ben Knight
  • High content analysis for tissue samples / Kristine Burke, Vaishali Sinde, Alice McDonald, Doug Bowman, Arijit Chakrivarty
  • Factoring and clustering high content data / Steven Haney, Arijit Chakravarty
  • Supervised machine learning / Jeff Palmer, Arijit Chakravarty.
Medical Library (Lane)
Book
1 online resource (767 p.)
Medicinal Chemistry of Anticancer Drugs, Second Edition, provides an updated treatment from the point of view of medicinal chemistry and drug design, focusing on the mechanism of action of antitumor drugs from the molecular level, and on the relationship between chemical structure and chemical and biochemical reactivity of antitumor agents. Antitumor chemotherapy is a very active field of research, and a huge amount of information on the topic is generated every year. Cytotoxic chemotherapy is gradually being supplemented by a new generation of drugs that recognize specific targets on the surface or inside cancer cells, and resistance to antitumor drugs continues to be investigated. While these therapies are in their infancy, they hold promise of more effective therapies with fewer side effects. Although many books are available that deal with clinical aspects of cancer chemotherapy, this book provides a sorely needed update from the point of view of medicinal chemistry and drug design. * Presents information in a clear and concise way using a large number of figures* Historical background provides insights on how the process of drug discovery in the anticancer field has evolved* Extensive references to primary literature.
(source: Nielsen Book Data)
Book
1 online resource (xi, 240 pages) : illustrations (some color).
  • Preface.- List of Contributors.- Engineering G Protein-Coupled Receptors for Drug Design-- M. Congreve et al.- Structural Insights into Activation and Allosteric Modulation of G Protein-Coupled Receptors-- A.C. Kruse.- Epigenetic Drug Discovery-- Chun-wa Chung.- Crystallography and Biopharmaceuticals-- R. Pauptit.- Structural Chemistry and Molecular Modeling in the Design of DPP4 Inhibitors-- G. Scapin.- Considerations for Structure-Based Drug Design Targeting HIV-1 Reverse Transcriptase-- E. Arnold et al.-Protein-Ligand Interactions as the Basis for Drug Action-- G. Klebe.- The Protein Data Bank: Overview and Tools for Drug Discovery-- H. M. Berman et al.- Small Molecule Crystal Structures in Drug Discovery-- C. Groom.- Protein Aggregation and its Prediction-- R. Grana-Montes, S.Ventura.- Importance of Protonation States for the Binding of Ligands to Pharmaceutical Targets-- A. Podjarny, E. Howard.- Protein-Protein Interactions: Structures and Druggability-- D.B. Ascher et al.- Achieving High Quality Ligand Chemistry in Protein-Ligand Crystal Structures for Drug Design-- O.S. Smart, G. Bricogne.- Molecular Obesity, Potency and Other Addictions in Drug Discovery-- M.M. Hann.- Adventures in Small Molecule Fragment Screening by X-ray Crystallography for Drug Discovery-- J.D. Bauman et al.- Structure-Based Drug Design to Perturb Function of a tRNA-Modifying Enzyme by Active Site and Protein-Protein Interface Inhibition-- G. Klebe.- Molecular Interaction Analysis for Discovery of Drugs Targeting Enzymes and for Resolving Biological Function-- U.H. Danielson.
  • (source: Nielsen Book Data)
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.
(source: Nielsen Book Data)
Book
1 online resource : text file, PDF
  • Prologue Jose L. Arias Key Aspects in Nanotechnology and Drug Delivery Jose L. Arias Drug Delivery and Release from Polymeric Nanomaterials Cornelia Vasile, Ana Maria Oprea, Manuela Tatiana Nistor and Anca-Maria Cojocariu Nano-Sized Polymeric Drug Carrier Systems Cornelia Vasile, Manuela Tatiana Nistor and Anca-Maria Cojocariu Reversible Cross-Linked Polymeric Nanoplatform in Drug Delivery Yuanpei Li, Kai Xiao and Kit S. Lam Cyclodextrins in Drug Delivery Nazli Erdogar and Erem Bilensoy Drug Delivery Systems Based on Tyrosine-derived Nanospheres (TyroSpheresTM) Zheng Zhang, Tannaz Ramezanli, Pei-Chin Tsai and Bozena B. Michniak-Kohn Carbon Nanotubes for Drug Delivery Applications Yitzhak Rosen and Pablo Gurman Metallic Nanoparticulate Drug Delivery Systems Varsha B. Pokharkar, Vividha V. Dhapte and Shivajirao S. Kadam Porous Silica Nanoparticles for Drug Delivery and Controlled Release Xiaoxing Sun and Brian G. Trewyn Iron Oxides in Drug Delivery Fahima Dilnawaz and Sanjeeb Kumar Sahoo Nanoengineered Magnetic Field-Induced Targeted Drug Delivery System with Stimuli Responsive Release R. Devesh K. Misra.
  • (source: Nielsen Book Data)
Pharmacotherapy is often limited by the inefficient activity and severe toxicity of drug molecules. Nanotechnology offers a revolutionary and definitive approach for the efficient delivery of drug molecules to non-healthy tissues and cells. This first volume of a series of two volumes analyzes the basics in the development of drug-loaded nanoplatforms, the so-called nanomedicines. Special attention is given to physicochemical engineering, pharmacokinetics, biocompatibility and biodegradability, representative nanoplatforms (based on lipids, polymers, cyclodextrins, metals, carbon, silica, iron oxides, etc.), and advanced nano-engineering strategies for passive, ligand-mediated, and/or stimuli-sensitive drug delivery and release.
(source: Nielsen Book Data)
Book
1 online resource.
  • Preface xi List of Contributors xv 1 Peptide Therapeutics 1 Nader Fotouhi 1.1 History of Peptides as Drugs 1 1.2 Factors Limiting the Use of Peptides in the Clinic 2 1.3 Advances That Have Stimulated the Use of Peptides as Drugs 3 1.4 Development of Peptide Libraries 4 1.5 Modification of Peptides to Promote Stability and Cell Entry 6 1.6 Targeting Peptides to Specific Cells 7 1.7 Formulations to Improve Properties 7 References 8 2 Methods for the Peptide Synthesis and Analysis 11 Judit Tulla-Puche, Ayman El-Faham, Athanassios S. Galanis, Eliandre de Oliveira, Aikaterini A. Zompra, and Fernando Albericio 2.1 Introduction 11 2.2 Solid Supports 13 2.3 Linkers 15 2.4 Protecting Groups 17 2.4.1 The Special Case of Cysteine 18 2.5 Methods for Peptide Bond Formation 20 2.5.1 Peptide-Bond Formation from Carbodiimide-Mediated Reactions 20 2.5.2 Peptide-Bond Formation from Preformed Symmetric Anhydrides 22 2.5.3 Peptide-Bond Formation from Acid Halides 23 2.5.4 Peptide-Bond Formation from Phosphonium Salt-Mediated Reactions 23 2.5.5 Peptide-Bond Formation from Aminium/Uronium Salt-Mediated Reactions 24 2.6 Solid-Phase Stepwise Synthesis 26 2.6.1 Long Peptides 27 2.7 Synthesis in Solution 29 2.7.1 NProtection of the N-Terminal Amino Acid Derivative or Fragment 30 2.7.2 Carboxy-Group Protection of the C-terminal Amino-Acid Derivative or Fragment 31 2.7.3 Peptide Bond Formation 34 2.8 Hybrid Synthesis Combination of Solid and Solution Synthesis 34 2.8.1 Classical Segment Condensation 35 2.8.2 Native Chemical Ligation 36 2.9 Cyclic Peptides 37 2.10 Depsipeptides 38 2.11 Separation and Purification of Peptides 40 2.11.1 Gel-Filtration Chromatography 41 2.11.2 Ion-Exchange Chromatography 41 2.11.3 Reverse-Phase High Performance Liquid Chromatography 42 2.12 Characterization of Peptides Through Mass Spectrometry 43 2.12.1 Ionization Source 44 2.12.2 Mass Analysers 45 2.12.3 Peptide Fragmentation 49 2.12.4 Quantification by MS 51 2.13 Conclusions 52 Acknowledgments 53 Abbreviations 53 References 56 3 Peptide Design Strategies for G-Protein Coupled Receptors (GPCRs) 75 Anamika Singh and Carrie Haskell-Luevano 3.1 Introduction 75 3.2 Classification of GPCRs 76 3.3 Catalog of Peptide-Activated G-Protein Coupled Receptors 77 3.4 Structure of GPCRs: Common Features 77 3.4.1 Crystal Structures 77 3.5 GPCR Activation 93 3.5.1 Ligand (Peptide) Binding and Receptor Activation 94 3.5.2 Common Structural Changes among GPCRs 95 3.5.3 G-Protein Coupled Intracellular Signaling Pathways 95 3.6 Structure and Function of Peptide Hormones 98 3.7 Design Approaches for GPCR Selective Peptide Ligands 98 3.7.1 Structure Activity Relationship (SAR) Studies 99 3.7.2 Chimeric Peptide Analogs 103 3.7.3 Combinatorial Libraries 103 3.7.4 Three-Dimensional (3D) GPCR Homology Molecular Modeling 104 3.8 Conclusions 105 Acknowledgments 105 References 105 4 Peptide-Based Inhibitors of Enzymes 113 Anna Knapinska, Sabrina Amar, Trista K. Robichaud, and Gregg B. Fields 4.1 Introduction 113 4.2 Angiotensin-Converting Enzyme and Neprilysin/Neutral Endopeptidase 114 4.3 Peptide Inhibitors of the HIV-1 Viral Life Cycle 117 4.4 Matrix Metalloproteinases 118 4.5 Antrax Lethal Factor Inhibition by Defensins 125 4.6 Kinases 127 4.7 Glycosyltransferases (Oligosaccharyltransferases) 131 4.8 Telomerase Inhibitors 134 4.9 Tyrosinase 138 4.10 Peptidyl-Prolyl Isomerase 140 4.11 Histone Modifying Enzymes 143 4.11.1 Histone Deacetylase 144 4.11.2 Histone Methyl-Transferase 145 4.12 Putting it all Together: Peptide Inhibitor Applications in Skin Care 146 4.13 Strategies for the Discovery of Novel Peptide Inhibitors 147 Acknowledgments 148 References 148 5 Discovery of Peptide Drugs as Enzyme Inhibitors and Activators 157 Jeffrey-Tri Nguyen and Yoshiaki Kiso 5.1 Introduction 157 5.1.1 Peptide Residue Nomenclature 158 5.1.2 Common Methods of Drug Design 159 5.1.3 Phases of Drug Development 163 5.2 Enzyme Types That Process Peptides 164 5.2.1 Enzymes as Chemicals in Consumer and Medical Products 164 5.2.2 Nonspecific Enzyme Inhibitors 166 5.3 Amino Acid Drugs 166 5.3.1 Thyroid Hormones 166 5.3.2 An Ornithine Decarboxylase Inhibitor 167 5.3.3 Catecholamines 168 5.4 Serine Proteases and Blood Clotting 169 5.4.1 Blood Coagulating Agents 170 5.4.2 Enzymes as Blood Anticoagulants 171 5.4.3 Direct Thrombin Inhibitors as Blood Anticoagulants 171 5.5 Diabetes Mellitus 174 5.5.1 Peptide Hormones and Blood Glucose Regulation 174 5.5.2 Glucagon-Like Peptide-1 and Analogs 175 5.5.3 Dipeptidyl Peptidase-4 Inhibitors 176 5.6 Renin Angiotensin Aldosterone System 178 5.6.1 ACE Inhibitors 178 5.6.2 Renin Inhibitors 180 5.7 Penicillin and Cephalosporin Antibiotics 183 5.8 HIV Protease 184 5.8.1 HIV-Specific Protease Inhibitors 185 5.9 Peptide Drugs Under Development 188 5.9.1 Cathepsins 188 5.9.2 Cysteine Proteases 189 5.9.3 Secretases in Alzheimer s Disease 189 5.9.4 Trypsin-Like Serine Proteases 190 5.9.5 Zinc Metalloproteases 190 5.9.6 Non-mammalian Proteases 191 5.10 Discussion 192 Acknowledgments 193 References 193 6 Discovery of Peptide Drugs from Natural Sources 203 Sonia T. Henriques and David J. Craik 6.1 Introduction 203 6.2 Peptides are Involved in the Host Defense Mechanism of Living Organisms 206 6.2.1 Cationic AMPs from Eukaryotes Peptides that Target the Membrane 207 6.2.2 Peptides and the Host Defense in Bacteria Bacteriocins 211 6.2.3 Cyclotides Ultra-Stable Peptides that are Part of Plant Defense Mechanism 216 6.3 Animal Venoms a Rich Source of Peptides with Therapeutic Potential 219 6.3.1 Conotoxins a Naturally Occurring Combinatorial Peptide Library 219 6.4 Optimization of Peptides for Drug Development 224 6.4.1 Chemical Modifications to Improve Activity 224 6.5 Conclusions 227 Acknowledgments 227 References 227 7 Modification of Peptides to Limit Metabolism 247 Isuru R. Kumarasinghe and Victor J. Hruby 7.1 Introduction 247 7.2 Introduction of Unnatural Amino Acids 248 7.3 Cyclization of Linear Peptides to Improve Stability Toward Blood and Brain Protease Degradation 249 7.4 Introduction of D-Amino Acids into Peptides Improves Stability Toward Blood and Brain Protease Degradation 253 7.5 Introduction of -Amino Acids Increases the Stability Toward Blood and Brain Protease Degradation 254 7.6 Introduction of Peptide Bond Isosteres 255 7.7 Introduction of a N-Methylation of the Amide Bond of Peptides Can Improve the Stability Toward Blood and Brain Protease Degradation 258 7.8 Use of Unnatural Amino Acids Use of Topographically Constrained Amino Acid 260 7.9 Using Glycosylated Amino Acids to Increase the Resistance of the Proteolytic Degradation 261 7.10 Creation of Peptides as Multiple Antigen Peptide (MAP) Dendrimeric Forms Increases the Stability Toward Blood and Brain Protease Degradation 262 7.11 Halogenations of Aromatic Residues in Peptides Can Reduce the Enzymatic Recognition Required for Peptide Hydrolysis 263 7.12 Concluding Discussion 264 References 265 8 Delivery of Peptide Drugs 271 Jeffrey-Tri Nguyen and Yoshiaki Kiso 8.1 Introduction 271 8.2 Lipinski s Rule of Five 271 8.2.1 Molecular Size 272 8.2.2 Lipophilicity 274 8.2.3 Chemical Stability 278 8.2.4 Routes of Administration 282 8.3 Approaches to Delivering Peptide Drugs 282 8.3.1 Enzyme Inhibitors 283 8.3.2 Permeation Enhancers 284 8.3.3 Delivery of Peptide Drugs across the Blood Brain Barrier 286 8.4 Parenteral Peptide Drugs 290 8.5 Topical Peptide Drugs for Local Effects 294 8.5.1 Cosmeceutical Peptides 294 8.6 Intranasal Peptide Drug Delivery 295 8.7 Enteral Peptide Drugs 297 8.8 Different Routes of Administration for Insulin 299 8.9 Discussion 300 Acknowledgments 301 References 301 Index 311.
  • (source: Nielsen Book Data)
This book focuses on peptides as drugs, a growing area of pharmaceutical research and development. It helps readers solve problems of discovering, developing, producing, and delivering peptide-based drugs. Identifies promising new areas in peptide drug discovery Includes chapters on discovery from natural sources, metabolic modification, and drug delivery Overviews separation methods and techniques for analysis, bond formation, and purification Offers readers both a professional reference and a text or resource for graduate-level students.
(source: Nielsen Book Data)
Book
1 online resource : illustrations.
This book is not going to be an exhaustive survey covering all aspects of rational drug design. Instead, it is going to provide critical know-how through real-world examples. Relevant case studies will be presented and analyzed to illustrate the following: how to optimize a lead compound whether one has high or low levels of structural information; how to derive hits from competitors' active compounds or from natural ligands of the targets; how to springboard from competitors' SAR knowledge in lead optimization; how to design a ligand to interfere with protein-protein interactions by correctly examining the PPI interface; how to circumvent IP blockage using data mining; how to construct and fully utilize a knowledge-based molecular descriptor system; how to build a reliable QSAR model by focusing on data quality and proper selection of molecular descriptors and statistical approaches. A Practical Guide to Rational Drug Design focuses on computational drug design, with only basic coverage of biology and chemistry issues, such as assay design, target validation and synthetic routes. Discusses various�tactics applicable to daily drug design Readers can download the materials used in the book, including structures, scripts, raw data, protocols, and codes, making this book suitable resource for short courses or workshopsOffers a unique viewpoint on drug discovery research due to the author's cross-discipline education background�Explores the�author's rich experiences in both pharmaceutical and academic settings.
(source: Nielsen Book Data)
Book
1 online resource.
The Practice of Medicinal Chemistry, Fourth Edition provides a practical and comprehensive overview of the daily issues facing pharmaceutical researchers and chemists. In addition to its thorough treatment of basic medicinal chemistry principles, this updated edition has been revised to provide new and expanded coverage of the latest technologies and approaches in drug discovery. With topics like high content screening, scoring, docking, binding free energy calculations, polypharmacology, QSAR, chemical collections and databases, and much more, this book is the go-to reference for all academic and pharmaceutical researchers who need a complete understanding of medicinal chemistry and its application to drug discovery and development. * Includes updated and expanded material on systems biology, chemogenomics, computer-aided drug design, and other important recent advances in the field* Incorporates extensive color figures, case studies, and practical examples to help users gain a further understanding of key concepts * Provides high-quality content in a comprehensive manner, including contributions from international chapter authors to illustrate the global nature of medicinal chemistry and drug development research* An image bank is available for instructors at www.textbooks.elsevier.com.
(source: Nielsen Book Data)
Book
1 online resource.
  • Front Cover; The Practice of Medicinal Chemistry; Copyright Page; Contents; List of Contributors; Foreword; Preface to the Fourth Edition; Preface to the Third Edition; Preface to the Second Edition; Preface to the First Edition; I. General Aspects of Medicinal Chemistry; 1 Medicinal Chemistry: Definitions and Objectives, Drug Activity Phases, Drug Classification Systems; I. Definitions and Objectives; A Medicinal Chemistry and Related Disciplines and Terms; B Drugs and Drug Substances; C Stages of Drug Development; II. Drug Activity Phases; A The Pharmaceutical Phase
  • B The Pharmacokinetic PhaseC The Pharmacodynamic Phase; D The Road to Successful Drug Development?; III. Drug Classification Systems; A Classification by Target and Mechanism of Action; 1 Targets; 2 Mechanisms of Action; B Other Classification Systems; References; 2 Evaluation of the Biological Activity of Compounds: Techniques and Mechanism of Action Studies; I. Introduction; II. Drug Discovery Approaches and Screening Cascades; A Target Based Screening; B Phenotypic Screening; III. In Vitro Assays; A Primary Assays; Glossary; 1 Binding assays; 2 Binding Studies: Principles and Analysis
  • 3 Enzyme Assays4 Types of Enzyme Inhibition and Their Analysis; A Reversible Inhibitors; B Irreversible Inhibitors; C Competitive Inhibitors; D Noncompetitive Inhibitors; E Uncompetitive Inhibitors; 5 Functional Assays; 6 Functional Studies and Their Analysis; A Agonist Concentration-Effect (E/[A]) Curves; B Full Agonists, Partial Agonists, and Inverse Agonists; C Optimizing Agonists; D Analysis of Antagonists; Competitive Antagonists; Irreversible, Noncompetitive, and Allosteric Antagonists; B Compound Interference in Primary Assays: Artifacts and False Positives; C Assay Biostatistics
  • D Selectivity, Cytotoxicity, and Species Cross-over.1 Selectivity; 2 Cytotoxicity; 3 Species Crossover; E Cellular and Tissue Functional Responses; IV. Ex Vivo Assays; V. In Vivo Assays; A Pharmacokinetic Models; B Efficacy Models; C Safety Testing; Acknowledgements; References; 3 Drug Targets, Target Identification, Validation, and Screening; I. Introduction; II. What is a Drug Target?; III. The Purpose of Target Identification; A Target-Based Screening; B Phenotypic Screening; C Fast Follower Strategy; IV. Target Options and Treatment Options; V. Target Deconvolution and Target Discovery
  • VI. Methods for Target Identification and ValidationA Affinity Chromatography; B Genetic Methods; C Haploinsufficiency Profiling in Yeast; D Analysis of Resistant Mutants; E siRNA for Target Validation; F Yeast Three-Hybrid System; G DNA Microarrays; H Comparative Profiling; I Analysis of the Pathophysiology; J The Study of Existing Drugs; K Systems Biology; L In Silico Simulation of the Human Patient; VII. Target Validation; VIII. Conclusion; References; II. Lead Compound Discovery Strategies; 4 Strategies in the Search for New Lead Compounds or Original Working Hypotheses; I. Introduction
The Practice of Medicinal Chemistry, Fourth Edition provides a practical and comprehensive overview of the daily issues facing pharmaceutical researchers and chemists. In addition to its thorough treatment of basic medicinal chemistry principles, this updated edition has been revised to provide new and expanded coverage of the latest technologies and approaches in drug discovery. With topics like high content screening, scoring, docking, binding free energy calculations, polypharmacology, QSAR, chemical collections and databases, and much more, this book is the go-to reference for all academic and pharmaceutical researchers who need a complete understanding of medicinal chemistry and its application to drug discovery and development. * Includes updated and expanded material on systems biology, chemogenomics, computer-aided drug design, and other important recent advances in the field* Incorporates extensive color figures, case studies, and practical examples to help users gain a further understanding of key concepts * Provides high-quality content in a comprehensive manner, including contributions from international chapter authors to illustrate the global nature of medicinal chemistry and drug development research* An image bank is available for instructors at www.textbooks.elsevier.com.
(source: Nielsen Book Data)

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