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  • 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)
  • 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
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)
  • 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)
  • 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)
  • 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.
  • Preface to Second Edition Preface to First Edition Abbreviations 1 Basic ideas in clinical trial design 2 Sampling and inferential statistics 3 Confidence intervals and p-values 4 Tests for simple treatment comparisons 5 Adjusting the analysis 6 Regression and analysis of covariance 7 Intention-to-treat and analysis sets 8 Power and sample size 9 Statistical significance and clinical importance 10 Multiple testing 11 Non-parametric and related methods 12 Equivalence and non-inferiority 13 The analysis of survival data 14 Interim analysis and data monitoring committees 15 Bayesian statistics 16 Adaptive Designs 17 Observational studies 18 Meta-analysis 19 Methods for the Safety Analysis and Safety Monitoring 20 Diagnosis 21 The role of statistics and statisticians References Index.
  • (source: Nielsen Book Data)
Statistical Thinking for Non-Statisticians in Drug Regulation, Second Edition, is a need-to-know guide to understanding statistical methodology, data and results within drug development and clinical trials for anyone working in the pharmaceutical and medical device industries. This new edition includes four new chapters covering Bayesian statistics, adaptive designs, observational studies and methods for safety analysis and monitoring.
(source: Nielsen Book Data)
  • Preface to Second Edition Preface to First Edition Abbreviations 1 Basic ideas in clinical trial design 2 Sampling and inferential statistics 3 Confidence intervals and p-values 4 Tests for simple treatment comparisons 5 Adjusting the analysis 6 Regression and analysis of covariance 7 Intention-to-treat and analysis sets 8 Power and sample size 9 Statistical significance and clinical importance 10 Multiple testing 11 Non-parametric and related methods 12 Equivalence and non-inferiority 13 The analysis of survival data 14 Interim analysis and data monitoring committees 15 Bayesian statistics 16 Adaptive Designs 17 Observational studies 18 Meta-analysis 19 Methods for the Safety Analysis and Safety Monitoring 20 Diagnosis 21 The role of statistics and statisticians References Index.
  • (source: Nielsen Book Data)
Statistical Thinking for Non-Statisticians in Drug Regulation, Second Edition, is a need-to-know guide to understanding statistical methodology, data and results within drug development and clinical trials for anyone working in the pharmaceutical and medical device industries. This new edition includes four new chapters covering Bayesian statistics, adaptive designs, observational studies and methods for safety analysis and monitoring.
(source: Nielsen Book Data)
Book
1 online resource
  • Part I: General Aspects. Serendipitous Target-Based Drug Discoveries / János Fischer, David P Rotella
  • Drug Discoveries and Molecular Mechanism of Action / David C Swinney
  • Part II: Drug Class. Insulin Analogs - Improving the Therapy of Diabetes / John M Beals
  • Part III: Case Histories. The Discovery of Stendra (Avanafil) for the Treatment of Erectile Dysfunction / Koichiro Yamada, Toshiaki Sakamoto, Kenji Omori, Kohei Kikkawa
  • Dapagliflozin, A Selective SGLT2 Inhibitor for Treatment of Diabetes / William N Washburn
  • Elvitegravir, A New HIV-1 Integrase Inhibitor for Antiretroviral Therapy / Hisashi Shinkai
  • Discovery of Linagliptin for the Treatment of Type 2 Diabetes Mellitus / Matthias Eckhardt, Thomas Klein, Herbert Nar, Sandra Thiemann
  • The Discovery of Alimta (Pemetrexed) / Edward C Taylor
  • Perampanel: A Novel, Noncompetitive AMPA Receptor Antagonist for the Treatment of Epilepsy / Shigeki Hibi
  • Discovery and Development of Telaprevir (Incivek): A Protease Inhibitor to Treat Hepatitis C Infection / Bhisetti G Rao, Mark Murcko, Mark J Tebbe, Ann D Kwong
  • Antibody-Drug Conjugates: Design and Development of Trastuzumab Emtansine (T-DM1) / Sandhya Girish, Gail D Lewis Phillips, Fredric S Jacobson, Jagath R Junutula, Ellie Guardino.
  • Part I: General Aspects. Serendipitous Target-Based Drug Discoveries / János Fischer, David P Rotella
  • Drug Discoveries and Molecular Mechanism of Action / David C Swinney
  • Part II: Drug Class. Insulin Analogs - Improving the Therapy of Diabetes / John M Beals
  • Part III: Case Histories. The Discovery of Stendra (Avanafil) for the Treatment of Erectile Dysfunction / Koichiro Yamada, Toshiaki Sakamoto, Kenji Omori, Kohei Kikkawa
  • Dapagliflozin, A Selective SGLT2 Inhibitor for Treatment of Diabetes / William N Washburn
  • Elvitegravir, A New HIV-1 Integrase Inhibitor for Antiretroviral Therapy / Hisashi Shinkai
  • Discovery of Linagliptin for the Treatment of Type 2 Diabetes Mellitus / Matthias Eckhardt, Thomas Klein, Herbert Nar, Sandra Thiemann
  • The Discovery of Alimta (Pemetrexed) / Edward C Taylor
  • Perampanel: A Novel, Noncompetitive AMPA Receptor Antagonist for the Treatment of Epilepsy / Shigeki Hibi
  • Discovery and Development of Telaprevir (Incivek): A Protease Inhibitor to Treat Hepatitis C Infection / Bhisetti G Rao, Mark Murcko, Mark J Tebbe, Ann D Kwong
  • Antibody-Drug Conjugates: Design and Development of Trastuzumab Emtansine (T-DM1) / Sandhya Girish, Gail D Lewis Phillips, Fredric S Jacobson, Jagath R Junutula, Ellie Guardino.
Book
1 online resource (xiii, 550 pages) : illustrations (some color).
  • 1 Hybrid QM/MM Methods: Treating Electronic Phenomena in Very Large Molecular Systems.- 2 Structure, Thermodynamics and Energetics of Drug-DNA Interactions: Computer Modeling and Experiment.- 3 Formation of DNA Lesions, Its Prevention and Repair.- 4 DNA dependent DNA Polymerases as Targets for Low-Weight Molecular Inhibitors: State of Art and Prospects of Rational Design.- 5 Molecular structures, relative stability, and proton affinities of nucleotides: Broad view and novel findings.- 6 Quantum Chemical Approaches in Modeling the Structure of Quadruplex DNA and Its Interaction with Metal Ions and Small Molecules.- 7 Density Functional Theory Calculations of Enzyme-Inhibitor Interactions in Medicinal Chemistry and Drug Design.- 8 Molecular Dynamics Simulations of Lipid Bilayers with Incorporated Peptides.- 9 Polyphenol Glycosides as Potential Remedies in Kidney Stones Therapy. Experimental Research Supported by Computational Studies.- 10 Quantum-Chemical Investigation of Epoxidic Compounds Transformation. Application for In Vitro and In Vivo Processes Modeling.- 11 Computational Toxicology in Drug Discovery: opportunities and limitations.- 12 Consensus Drug Design Using it Microcosm.- 13 Continuous Molecular Fields Approach Applied to Structure-Activity Modeling.- 14 Quantitative Structure-Pharmacokinetic Relationships of Drugs within the Framework of Biopharmaceutics Classification System by Using Simplex Representation of Molecular Structure.- 15 (How to) Profit from Molecular Dynamics-based Ensemble Docking.- 16 Cheminformatics on Crossroad of Eras.
  • (source: Nielsen Book Data)
The proposed volume provides both fundamental and detailed information about the computational and computational-experimental studies which improve our knowledge of how leaving matter functions, the different properties of drugs (including the calculation and the design of new ones), and the creation of completely new ways of treating numerical diseases. Whenever it is possible, the interplay between theory and experiment is provided. The book features computational techniques such as quantum-chemical and molecular dynamic approaches and quantitative structure-activity relationships. The initial chapters describe the state-of-the art research on the computational investigations in molecular biology, molecular pharmacy, and molecular medicine performed with the use of pure quantum-chemical techniques. The central part of the book illustrates the status of computational techniques that utilize hybrid, so called QM/MM approximations as well as the results of the QSAR studies which now are the most popular in predicting drugs' efficiency. The last chapters describe combined computational and experimental investigations.
(source: Nielsen Book Data)
  • 1 Hybrid QM/MM Methods: Treating Electronic Phenomena in Very Large Molecular Systems.- 2 Structure, Thermodynamics and Energetics of Drug-DNA Interactions: Computer Modeling and Experiment.- 3 Formation of DNA Lesions, Its Prevention and Repair.- 4 DNA dependent DNA Polymerases as Targets for Low-Weight Molecular Inhibitors: State of Art and Prospects of Rational Design.- 5 Molecular structures, relative stability, and proton affinities of nucleotides: Broad view and novel findings.- 6 Quantum Chemical Approaches in Modeling the Structure of Quadruplex DNA and Its Interaction with Metal Ions and Small Molecules.- 7 Density Functional Theory Calculations of Enzyme-Inhibitor Interactions in Medicinal Chemistry and Drug Design.- 8 Molecular Dynamics Simulations of Lipid Bilayers with Incorporated Peptides.- 9 Polyphenol Glycosides as Potential Remedies in Kidney Stones Therapy. Experimental Research Supported by Computational Studies.- 10 Quantum-Chemical Investigation of Epoxidic Compounds Transformation. Application for In Vitro and In Vivo Processes Modeling.- 11 Computational Toxicology in Drug Discovery: opportunities and limitations.- 12 Consensus Drug Design Using it Microcosm.- 13 Continuous Molecular Fields Approach Applied to Structure-Activity Modeling.- 14 Quantitative Structure-Pharmacokinetic Relationships of Drugs within the Framework of Biopharmaceutics Classification System by Using Simplex Representation of Molecular Structure.- 15 (How to) Profit from Molecular Dynamics-based Ensemble Docking.- 16 Cheminformatics on Crossroad of Eras.
  • (source: Nielsen Book Data)
The proposed volume provides both fundamental and detailed information about the computational and computational-experimental studies which improve our knowledge of how leaving matter functions, the different properties of drugs (including the calculation and the design of new ones), and the creation of completely new ways of treating numerical diseases. Whenever it is possible, the interplay between theory and experiment is provided. The book features computational techniques such as quantum-chemical and molecular dynamic approaches and quantitative structure-activity relationships. The initial chapters describe the state-of-the art research on the computational investigations in molecular biology, molecular pharmacy, and molecular medicine performed with the use of pure quantum-chemical techniques. The central part of the book illustrates the status of computational techniques that utilize hybrid, so called QM/MM approximations as well as the results of the QSAR studies which now are the most popular in predicting drugs' efficiency. The last chapters describe combined computational and experimental investigations.
(source: Nielsen Book Data)

9. Chemistry of drugs [2014]

Book
x, 260 p. : ill. ; 24 cm.
Chemistry & ChemEng Library (Swain)
Status of items at Chemistry & ChemEng Library (Swain)
Chemistry & ChemEng Library (Swain) Status
Stacks
RS403 .B27 2014 Unknown
Book
online resource (xii, 252 pages) : illustrations (some color)
This book focuses on applications of compound library design and virtual screening to expand the bioactive chemical space, to target hopping of chemotypes to identify synergies within related drug discovery projects or to repurpose known drugs, to propose mechanism of action of compounds, or to identify off-target effects by cross-reactivity analysis. Both ligand-based and structure-based in silico approaches, as reviewed in this book, play important roles for all these applications. Computational chemogenomics is expected to increase the quality and productivity of drug discovery and lead.
This book focuses on applications of compound library design and virtual screening to expand the bioactive chemical space, to target hopping of chemotypes to identify synergies within related drug discovery projects or to repurpose known drugs, to propose mechanism of action of compounds, or to identify off-target effects by cross-reactivity analysis. Both ligand-based and structure-based in silico approaches, as reviewed in this book, play important roles for all these applications. Computational chemogenomics is expected to increase the quality and productivity of drug discovery and lead.
Medical Library (Lane)
Status of items at Medical Library (Lane)
Medical Library (Lane) Status
Check Medical Library (Lane) catalog for status
CRCNETBASE Unknown
Book
1 online resource (xxiv, 553 pages)
Systematically examining current methods and strategies, this ready reference covers a wide range of molecular structures, from organic-chemical drugs to peptides, proteins and nucleic acids, in line with emerging new drug classes derived from biomacromolecules. A leader in the field and one of the pioneers of this young discipline has assembled here the most prominent experts from across the world to provide first-hand knowledge. While most of their methods and examples come from the area of pharmaceutical discovery and development, the approaches are equally applicable for molecular probes and diagnostics, pesticides, and any other molecule designed to interact with a biological system. Hundreds of images and screenshots, many of them in full color, illustrate the examples and method descriptions. With its broad and balanced coverage, this will be the first-stop resource for medicinal chemists, biochemists and biotechnologists for many years to come.
(source: Nielsen Book Data)
Systematically examining current methods and strategies, this ready reference covers a wide range of molecular structures, from organic-chemical drugs to peptides, proteins and nucleic acids, in line with emerging new drug classes derived from biomacromolecules. A leader in the field and one of the pioneers of this young discipline has assembled here the most prominent experts from across the world to provide first-hand knowledge. While most of their methods and examples come from the area of pharmaceutical discovery and development, the approaches are equally applicable for molecular probes and diagnostics, pesticides, and any other molecule designed to interact with a biological system. Hundreds of images and screenshots, many of them in full color, illustrate the examples and method descriptions. With its broad and balanced coverage, this will be the first-stop resource for medicinal chemists, biochemists and biotechnologists for many years to come.
(source: Nielsen Book Data)
Book
1 online resource (xi, 511 pages) : illustrations (some color).
Book
online resource (xi, 511 pages) : illustrations (some color).
  • Part I. Strategy and tactics that enable discovery
  • Part II. Predictive approaches to establishing, understanding and communicating risk in early development
  • Part III. Use of physicochemical properties for preclinical formulation selection and early clinical formulations.
This authoritative volume provides a contemporary view on the latest research in molecules with optimal drug-like properties. It is a valuable source to access current best practices as well as new research techniques and strategies. Written by leading scientists in their fields, the text consists of fourteen chapters with an underlying theme of early collaborative opportunities between pharmaceutical and discovery sciences. The book explores the practical realities of performing physical pharmaceutical and biopharmaceutical research in the context of drug discovery with short timelines and low compound availability. Chapters cover strategies and tactics to enable discovery as well as predictive approaches to establish, understand and communicate risks in early development. It also examines the detection, characterization and assessment of risks on the solid state properties of advanced discovery and early development candidates, highlighting the link between solid state properties and critical development parameters such as solubility and stability. Final chapters center on techniques to improve molecular solubilization and prevent precipitation, with particularly emphasis on linking physiochemical properties of molecules to formulation selection in preclinical and clinical settings.
  • Part I. Strategy and tactics that enable discovery
  • Part II. Predictive approaches to establishing, understanding and communicating risk in early development
  • Part III. Use of physicochemical properties for preclinical formulation selection and early clinical formulations.
This authoritative volume provides a contemporary view on the latest research in molecules with optimal drug-like properties. It is a valuable source to access current best practices as well as new research techniques and strategies. Written by leading scientists in their fields, the text consists of fourteen chapters with an underlying theme of early collaborative opportunities between pharmaceutical and discovery sciences. The book explores the practical realities of performing physical pharmaceutical and biopharmaceutical research in the context of drug discovery with short timelines and low compound availability. Chapters cover strategies and tactics to enable discovery as well as predictive approaches to establish, understand and communicate risks in early development. It also examines the detection, characterization and assessment of risks on the solid state properties of advanced discovery and early development candidates, highlighting the link between solid state properties and critical development parameters such as solubility and stability. Final chapters center on techniques to improve molecular solubilization and prevent precipitation, with particularly emphasis on linking physiochemical properties of molecules to formulation selection in preclinical and clinical settings.
Medical Library (Lane)
Status of items at Medical Library (Lane)
Medical Library (Lane) Status
Check Medical Library (Lane) catalog for status
SPRINGER Unknown
Book
online resource (xx, 731 pages) : illustrations ; 24 cm
  • Part I. Physiology and basic principles for drug handling by the brain
  • Part II. Pharmacokinetic concepts in brain drug delivery
  • Part III. Industrial approaches for investigation of potential central nervous system drugs
  • Part IV. Strategies for improved central nervous system drug delivery
  • Part V. Brain drug delivery in disease conditions.
This book describes the different approaches for drug delivery to the brain with an emphasis on the physiology of the blood-brain barrier (BBB) and the governing principles and concepts for drug delivery across the BBB. It contains cutting-edge methods for studying drug delivery and administering drugs into the brain. The book also explores different approaches for predicting human brain concentrations as well as the influence of disease and drug industry perspectives. In addition to wide-ranging coverage of physiological concepts relevant to central nervous system (CNS) drug delivery, a detailed review of brain structure, function, blood supply and fluids is also provided. In each chapter, descriptions of future challenges and unresolved questions are combined with points for discussion. This unique combination of material makes this book a valuable resource for students and for established academic and industry scientists looking to learn about state-of-the-art drug delivery research. It is also a source for stimulating new ideas among experts already performing CNS drug delivery research or working in related areas. Margareta Hammarlund-Udenaes (Ph.D.) is a Professor in Pharmacokinetics and Pharmacodynamics (PK/PD) at Uppsala University and the Head of the Translational PK/PD Group. Her research is focused on studying pharmacokinetic aspects of BBB transport of drugs in relation to CNS effects, and it has led to the development of new concepts and methods within the BBB transport area, focusing on unbound drug relationships. Elizabeth C.M. de Lange (Ph.D.) is Head of the Target Site Equilibration Group at the Division of Pharmacology of the Leiden Academic Center for Drug Research (LACDR). Her research program focuses on the development of generally applicable predictive PK/PD models on CNS drugs using advanced in vivo animal models and mathematical modeling techniques, with a number of recent successes. Robert G. Thorne (Ph.D.) is an Assistant Professor in Pharmaceutical Sciences at the University of Wisconsin-Madison School of Pharmacy. He was previously a research scientist and faculty member in the Department of Physiology & Neuroscience at the New York University School of Medicine. His research focuses on diffusive and convective transport within the CNS and the development, refinement and optimization of strategies for delivering biologics into the brain.
  • Part I. Physiology and basic principles for drug handling by the brain
  • Part II. Pharmacokinetic concepts in brain drug delivery
  • Part III. Industrial approaches for investigation of potential central nervous system drugs
  • Part IV. Strategies for improved central nervous system drug delivery
  • Part V. Brain drug delivery in disease conditions.
This book describes the different approaches for drug delivery to the brain with an emphasis on the physiology of the blood-brain barrier (BBB) and the governing principles and concepts for drug delivery across the BBB. It contains cutting-edge methods for studying drug delivery and administering drugs into the brain. The book also explores different approaches for predicting human brain concentrations as well as the influence of disease and drug industry perspectives. In addition to wide-ranging coverage of physiological concepts relevant to central nervous system (CNS) drug delivery, a detailed review of brain structure, function, blood supply and fluids is also provided. In each chapter, descriptions of future challenges and unresolved questions are combined with points for discussion. This unique combination of material makes this book a valuable resource for students and for established academic and industry scientists looking to learn about state-of-the-art drug delivery research. It is also a source for stimulating new ideas among experts already performing CNS drug delivery research or working in related areas. Margareta Hammarlund-Udenaes (Ph.D.) is a Professor in Pharmacokinetics and Pharmacodynamics (PK/PD) at Uppsala University and the Head of the Translational PK/PD Group. Her research is focused on studying pharmacokinetic aspects of BBB transport of drugs in relation to CNS effects, and it has led to the development of new concepts and methods within the BBB transport area, focusing on unbound drug relationships. Elizabeth C.M. de Lange (Ph.D.) is Head of the Target Site Equilibration Group at the Division of Pharmacology of the Leiden Academic Center for Drug Research (LACDR). Her research program focuses on the development of generally applicable predictive PK/PD models on CNS drugs using advanced in vivo animal models and mathematical modeling techniques, with a number of recent successes. Robert G. Thorne (Ph.D.) is an Assistant Professor in Pharmaceutical Sciences at the University of Wisconsin-Madison School of Pharmacy. He was previously a research scientist and faculty member in the Department of Physiology & Neuroscience at the New York University School of Medicine. His research focuses on diffusive and convective transport within the CNS and the development, refinement and optimization of strategies for delivering biologics into the brain.
Medical Library (Lane)
Status of items at Medical Library (Lane)
Medical Library (Lane) Status
Check Medical Library (Lane) catalog for status
SPRINGER Unknown
Book
1 online resource (366 pages) : illustrations.
  • Contributors vii Preface ix Part A -Enzymes essential workhorses inpharmaceutical research 1 1 Assay Technologies for Proteases 3 Anuradha Roy, Gerald H. Lushington, James McGee, and RathnamChaguturu 2 Discovery and Development of Isozyme-Selective InhibitorsInvolved in Lipid Metabolism 55 Taichi Ohshiro and Hiroshi Tomoda 3 Covalent Enzyme Inhibition in Drug Discovery and Development81 Shujaath Mehdi 4 Preclinomics: Enzyme Assays and Rodent Models for Metabolicdiseases 131 Wu-Kuang Yeh and Richard G. Peterson Part B -Enzymes indispensable tools forimproving druggability 163 5 Enzymes and Targeted Activation of Prodrugs 165 Yanhui Yang, Yu Chen, Herve Aloysius, Daigo Inoyama, and LongqinHu 6 Evolution of an Orally Active Prodrug of Gemcitabine 237 James R. McCarthy 7 Enzymatically Activated Phosphate and Phosphonate Prodrugs253 Ivan S. Krylov and Charles E. McKenna Part C E nzymes powerful weapons for correctingNature s errors 301 8 Treatment Options for Mucopolysaccharidosis Type II(Hunter s Syndrome) 303 Michael Beck 9 Enzyme Replacement Therapy for Fabry Disease 321 Ley Nadine Lacbawan, Wei Zheng, and Ozlem Goker-Alpan 10 Methods and Principles of Pancreatic Function Tests 335 Henrike von Schassen, Jutta Keller, and Peter Layer Index 341.
  • (source: Nielsen Book Data)
Highlighting the critical importance of enzymes in pharmaceutical and biotechnology research, Enzyme Technologies presents thorough discussions on chemical biology of enzymes, redesigning binding and catalytic specificities of enzymes, and applications of enzymes to biotechnology research in the post-genomic era. This timely review presents researchers, students, and faculty with expert reviews of recent progress in comprehending molecular mechanisms of biosynthetic and biocatalytic processes as well as how to utilize that knowledge for practical applications.
(source: Nielsen Book Data)
  • Contributors vii Preface ix Part A -Enzymes essential workhorses inpharmaceutical research 1 1 Assay Technologies for Proteases 3 Anuradha Roy, Gerald H. Lushington, James McGee, and RathnamChaguturu 2 Discovery and Development of Isozyme-Selective InhibitorsInvolved in Lipid Metabolism 55 Taichi Ohshiro and Hiroshi Tomoda 3 Covalent Enzyme Inhibition in Drug Discovery and Development81 Shujaath Mehdi 4 Preclinomics: Enzyme Assays and Rodent Models for Metabolicdiseases 131 Wu-Kuang Yeh and Richard G. Peterson Part B -Enzymes indispensable tools forimproving druggability 163 5 Enzymes and Targeted Activation of Prodrugs 165 Yanhui Yang, Yu Chen, Herve Aloysius, Daigo Inoyama, and LongqinHu 6 Evolution of an Orally Active Prodrug of Gemcitabine 237 James R. McCarthy 7 Enzymatically Activated Phosphate and Phosphonate Prodrugs253 Ivan S. Krylov and Charles E. McKenna Part C E nzymes powerful weapons for correctingNature s errors 301 8 Treatment Options for Mucopolysaccharidosis Type II(Hunter s Syndrome) 303 Michael Beck 9 Enzyme Replacement Therapy for Fabry Disease 321 Ley Nadine Lacbawan, Wei Zheng, and Ozlem Goker-Alpan 10 Methods and Principles of Pancreatic Function Tests 335 Henrike von Schassen, Jutta Keller, and Peter Layer Index 341.
  • (source: Nielsen Book Data)
Highlighting the critical importance of enzymes in pharmaceutical and biotechnology research, Enzyme Technologies presents thorough discussions on chemical biology of enzymes, redesigning binding and catalytic specificities of enzymes, and applications of enzymes to biotechnology research in the post-genomic era. This timely review presents researchers, students, and faculty with expert reviews of recent progress in comprehending molecular mechanisms of biosynthetic and biocatalytic processes as well as how to utilize that knowledge for practical applications.
(source: Nielsen Book Data)
Book
1 online resource.
Increasing the potency of therapeutic compounds, while limiting side-effects, is a common goal in medicinal chemistry. Ligands that effectively bind metal ions and also include specific features to enhance targeting, reporting, and overall efficacy are driving innovation in areas of disease diagnosis and therapy. Ligand Design in Medicinal Inorganic Chemistry presents the state-of-the-art in ligand design for medicinal inorganic chemistry applications. Each individual chapter describes and explores the application of compounds that either target a disease site, or are activated by a disease-specific biological process. Ligand design is discussed in the following areas: * Platinum, Ruthenium, and Gold-containing anticancer agents * Emissive metal-based optical probes * Metal-based antimalarial agents * Metal overload disorders * Modulation of metal-protein interactions in neurodegenerative diseases * Photoactivatable metal complexes and their use in biology and medicine * Radiodiagnostic agents and Magnetic Resonance Imaging (MRI) agents * Carbohydrate-containing ligands and Schiff-base ligands in Medicinal Inorganic Chemistry * Metalloprotein inhibitors Ligand Design in Medicinal Inorganic Chemistry provides graduate students, industrial chemists and academic researchers with a launching pad for new research in medicinal chemistry.
(source: Nielsen Book Data)
Increasing the potency of therapeutic compounds, while limiting side-effects, is a common goal in medicinal chemistry. Ligands that effectively bind metal ions and also include specific features to enhance targeting, reporting, and overall efficacy are driving innovation in areas of disease diagnosis and therapy. Ligand Design in Medicinal Inorganic Chemistry presents the state-of-the-art in ligand design for medicinal inorganic chemistry applications. Each individual chapter describes and explores the application of compounds that either target a disease site, or are activated by a disease-specific biological process. Ligand design is discussed in the following areas: * Platinum, Ruthenium, and Gold-containing anticancer agents * Emissive metal-based optical probes * Metal-based antimalarial agents * Metal overload disorders * Modulation of metal-protein interactions in neurodegenerative diseases * Photoactivatable metal complexes and their use in biology and medicine * Radiodiagnostic agents and Magnetic Resonance Imaging (MRI) agents * Carbohydrate-containing ligands and Schiff-base ligands in Medicinal Inorganic Chemistry * Metalloprotein inhibitors Ligand Design in Medicinal Inorganic Chemistry provides graduate students, industrial chemists and academic researchers with a launching pad for new research in medicinal chemistry.
(source: Nielsen Book Data)
Book
1 online resource (viii, 202 pages) : illustrations (some color)
Book
1 online resource.
  • Introduction
  • Lead discovery and lead modification
  • Receptors
  • Enzymes
  • Enzyme inhibition and inactivation
  • Dna-interactive agents
  • Drug resistance and drug synergism
  • Drug metabolism
  • Prodrugs and drug delivery systems.
The Organic Chemistry of Drug Design and Drug Action, Third Edition, represents a unique approach to medicinal chemistry based on physical organic chemical principles and reaction mechanisms that rationalize drug action, which allows the reader to extrapolate those core principles and mechanisms to many related classes of drug molecules. This new edition reflects significant changes in the process of drug design over the last decade. It preserves the successful approach of the previous editions while including significant changes in format and coverage. New to this edition: * Updates to all chapters, including new examples and references* Chapter 1 (Introduction): Completely rewritten and expanded as an overview of topics discussed in detail throughout the book* Chapter 2 (Lead Discovery and Lead Modification): Sections on sources of compounds for screening including library collections, virtual screening, and computational methods, as well as hit-to-lead and scaffold hopping; expanded sections on sources of lead compounds, fragment-based lead discovery, and molecular graphics; and deemphasized solid-phase synthesis and combinatorial chemistry* Chapter 3 (Receptors): Drug-receptor interactions, cation-? and halogen bonding; atropisomers; case history of the insomnia drug suvorexant* Chapter 4 (Enzymes): Expanded sections on enzyme catalysis in drug discovery and enzyme synthesis* Chapter 5 (Enzyme Inhibition and Inactivation): New case histories: * for competitive inhibition, the epidermal growth factor receptor tyrosine kinase inhibitor, erlotinib and Abelson kinase inhibitor, imatinib* for transition state analogue inhibition, the purine nucleoside phosphorylase inhibitors, forodesine and DADMe-ImmH, as well as the mechanism of the multisubstrate analog inhibitor isoniazid* for slow, tight-binding inhibition, the dipeptidyl peptidase-4 inhibitor, saxagliptin* Chapter 7 (Drug Resistance and Drug Synergism): This new chapter includes topics taken from two chapters in the previous edition, with many new examples* Chapter 8 (Drug Metabolism): Discussions of toxicophores and reactive metabolites* Chapter 9 (Prodrugs and Drug Delivery Systems): Discussion of antibody-drug conjugates.
(source: Nielsen Book Data)
  • Introduction
  • Lead discovery and lead modification
  • Receptors
  • Enzymes
  • Enzyme inhibition and inactivation
  • Dna-interactive agents
  • Drug resistance and drug synergism
  • Drug metabolism
  • Prodrugs and drug delivery systems.
The Organic Chemistry of Drug Design and Drug Action, Third Edition, represents a unique approach to medicinal chemistry based on physical organic chemical principles and reaction mechanisms that rationalize drug action, which allows the reader to extrapolate those core principles and mechanisms to many related classes of drug molecules. This new edition reflects significant changes in the process of drug design over the last decade. It preserves the successful approach of the previous editions while including significant changes in format and coverage. New to this edition: * Updates to all chapters, including new examples and references* Chapter 1 (Introduction): Completely rewritten and expanded as an overview of topics discussed in detail throughout the book* Chapter 2 (Lead Discovery and Lead Modification): Sections on sources of compounds for screening including library collections, virtual screening, and computational methods, as well as hit-to-lead and scaffold hopping; expanded sections on sources of lead compounds, fragment-based lead discovery, and molecular graphics; and deemphasized solid-phase synthesis and combinatorial chemistry* Chapter 3 (Receptors): Drug-receptor interactions, cation-? and halogen bonding; atropisomers; case history of the insomnia drug suvorexant* Chapter 4 (Enzymes): Expanded sections on enzyme catalysis in drug discovery and enzyme synthesis* Chapter 5 (Enzyme Inhibition and Inactivation): New case histories: * for competitive inhibition, the epidermal growth factor receptor tyrosine kinase inhibitor, erlotinib and Abelson kinase inhibitor, imatinib* for transition state analogue inhibition, the purine nucleoside phosphorylase inhibitors, forodesine and DADMe-ImmH, as well as the mechanism of the multisubstrate analog inhibitor isoniazid* for slow, tight-binding inhibition, the dipeptidyl peptidase-4 inhibitor, saxagliptin* Chapter 7 (Drug Resistance and Drug Synergism): This new chapter includes topics taken from two chapters in the previous edition, with many new examples* Chapter 8 (Drug Metabolism): Discussions of toxicophores and reactive metabolites* Chapter 9 (Prodrugs and Drug Delivery Systems): Discussion of antibody-drug conjugates.
(source: Nielsen Book Data)
Book
online resource (xv, 439 pages) : illustrations (some color).
  • Pediatric Development: Anatomy
  • Age, Weight, Body Surface and Stature, Organ Development
  • Pediatric Development: Physiology. Enzymes, Drug Metabolism, Pharmacokinetics and Pharmacodynamics
  • Pediatric Development? Gastrointestinal
  • How to Estimate the Dose to be Given for the First Time to Pediatric Patients
  • The Clinical Relevance of Pediatric Formulations
  • General Considerations for Pediatric Oral Drug Formulation
  • Orosensory Perception
  • Flavor Is Not Just Taste: Taste Concealing
  • Liquid Formulations
  • Paediatric Solid Formulations
  • Semi-Solid Formulations
  • The Challenge of Automated Compounding
  • Pediatric Formulations in Clinical Testing and the Challenge of Final Market Formulation
  • Buccal/Sublingual Drug Delivery for the Paediatric Population
  • Topical and Transdermal
  • Parenteral Liquids for Intravenous and Transdermal Use
  • The Challenges of Paediatric Pulmonary Drug Delivery
  • Nasal, Ocular and Otic Drug Delivery
  • Rectal Drug Delivery
  • Intraosseous Infusions in Infants and Neonates
  • Compounding for Children? The Compounding Pharmacist
  • Food Ingredients
  • Excipients and Active Pharmaceutical Ingredients (APIs)
  • Clinical Testing in Children
  • Pediatric Formulations and Dosage Forms and Future Opportunities: Impact of Regulations in the United States and Implementation of Quality by Design
  • Pediatric Pharmaceutical Legislation and its impact on Adult and Pediatric Drug Development: The EU Regulatory View
  • Pediatric Pharmaceutical Legislation in USA and EU and their impact on Adult and Pediatric Drug Development
  • Checks and Balances in the EU: The Role of the European Ombudsman, with a Focus on the Paediatric Regulation
  • The Dangerous Business Of Predicting The Future.
As the first book that specifically addresses pediatric formulations in the context of drug development, Pediatric Formulations: A Roadmap covers anatomy and physiology of children as well as the technical state of the art, gives hints about where to find inspiration, and provides a suitable background on the regulatory framework. Existing books on pediatric formulations mainly discuss compounding at the pharmacy. This is not a "how to formulate" textbook for pharmaceutical scientists; the subtitle "A Roadmap" indicates that we are on a path in largely unexplored territory. It is an attempt to equip the reader with necessary information on how to get started with the appropriate mindset. Among medicinal specialties, pediatrics is a young discipline. The potential dangers of medicine were often underestimated in earlier times. Cough suppressants labeled as "suitable for children and adults" a hundred years ago could kill children as they contained opioids. Since then, a complex framework has evolved, with physicians, pharmacists, drug development companies, generic companies, academic scientists, regulatory authorities, reimbursement organizations, patients and children's parents as key players. The position of children in our society has changed dramatically during the last century. Children were protected against clinical trials, yet thanks to clinical trials, many more children with cancer survive today. The development of age-adjusted drug formulations is not only a technical challenge. For new drugs today, there are laws both in the United States and the European Union that compel the research-based pharmaceutical industry to also consider children during drug development. One of the major demands of authorities is the development of age-appropriate formulations.
  • Pediatric Development: Anatomy
  • Age, Weight, Body Surface and Stature, Organ Development
  • Pediatric Development: Physiology. Enzymes, Drug Metabolism, Pharmacokinetics and Pharmacodynamics
  • Pediatric Development? Gastrointestinal
  • How to Estimate the Dose to be Given for the First Time to Pediatric Patients
  • The Clinical Relevance of Pediatric Formulations
  • General Considerations for Pediatric Oral Drug Formulation
  • Orosensory Perception
  • Flavor Is Not Just Taste: Taste Concealing
  • Liquid Formulations
  • Paediatric Solid Formulations
  • Semi-Solid Formulations
  • The Challenge of Automated Compounding
  • Pediatric Formulations in Clinical Testing and the Challenge of Final Market Formulation
  • Buccal/Sublingual Drug Delivery for the Paediatric Population
  • Topical and Transdermal
  • Parenteral Liquids for Intravenous and Transdermal Use
  • The Challenges of Paediatric Pulmonary Drug Delivery
  • Nasal, Ocular and Otic Drug Delivery
  • Rectal Drug Delivery
  • Intraosseous Infusions in Infants and Neonates
  • Compounding for Children? The Compounding Pharmacist
  • Food Ingredients
  • Excipients and Active Pharmaceutical Ingredients (APIs)
  • Clinical Testing in Children
  • Pediatric Formulations and Dosage Forms and Future Opportunities: Impact of Regulations in the United States and Implementation of Quality by Design
  • Pediatric Pharmaceutical Legislation and its impact on Adult and Pediatric Drug Development: The EU Regulatory View
  • Pediatric Pharmaceutical Legislation in USA and EU and their impact on Adult and Pediatric Drug Development
  • Checks and Balances in the EU: The Role of the European Ombudsman, with a Focus on the Paediatric Regulation
  • The Dangerous Business Of Predicting The Future.
As the first book that specifically addresses pediatric formulations in the context of drug development, Pediatric Formulations: A Roadmap covers anatomy and physiology of children as well as the technical state of the art, gives hints about where to find inspiration, and provides a suitable background on the regulatory framework. Existing books on pediatric formulations mainly discuss compounding at the pharmacy. This is not a "how to formulate" textbook for pharmaceutical scientists; the subtitle "A Roadmap" indicates that we are on a path in largely unexplored territory. It is an attempt to equip the reader with necessary information on how to get started with the appropriate mindset. Among medicinal specialties, pediatrics is a young discipline. The potential dangers of medicine were often underestimated in earlier times. Cough suppressants labeled as "suitable for children and adults" a hundred years ago could kill children as they contained opioids. Since then, a complex framework has evolved, with physicians, pharmacists, drug development companies, generic companies, academic scientists, regulatory authorities, reimbursement organizations, patients and children's parents as key players. The position of children in our society has changed dramatically during the last century. Children were protected against clinical trials, yet thanks to clinical trials, many more children with cancer survive today. The development of age-adjusted drug formulations is not only a technical challenge. For new drugs today, there are laws both in the United States and the European Union that compel the research-based pharmaceutical industry to also consider children during drug development. One of the major demands of authorities is the development of age-appropriate formulations.
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Check Medical Library (Lane) catalog for status
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Book
1 online resource (320 pages) : illustrations
  • Preface xiii Abbreviations xvii PART I The Basics of Peptidomimetics 1 1. The Basics of Peptidomimetics 3 1.1 Introduction 3 1.2 Definition and Classification 5 1.3 Strategic Approaches to Peptidomimetic Design 7 1.3.1 Modification of Amino Acids 8 1.3.2 Compounds with Global Restrictions 9 1.3.3 Molecular Scaffolds Mimicking the Peptidic Backbone 10 1.4 Successful Examples of Peptidomimetic Drugs 12 1.4.1 ACE Inhibitors 13 1.4.2 Thrombin Inhibitors 13 1.5 Conclusion 16 References 16 2. Synthetic Approaches towards Peptidomimetic Design19 2.1 Introduction 19 2.2 Local Modifications 20 2.2.1 Single Amino Acid Modifications 23 2.2.2 Dipeptide Isosteres 26 2.2.3 Retro-inverso Peptides 29 2.2.4 N-Methylation of Peptides 30 2.2.5 Azapeptides 31 2.2.6 Peptoids 31 2.3 Global Restrictions through Cyclic Peptidomimetics 32 2.4 Peptidomimetic Scaffolds 34 2.5 Conclusions 35 References 35 PART II Synthetic Methods and Molecules 37 3. Peptidomimetic Bioisosteres 39 3.1 Introduction 39 3.2 Peptide Bond Isosteres 40 3.2.1 Thioamides 41 3.2.2 Esters 41 3.2.3 Alkenes and Fluoroalkenes 41 3.2.4 Transition-State Isosteres 42 3.3 Side-Chain Isosteres 45 3.3.1 Guanidine Isosteres in Arginine Peptidomimetics 45 3.3.2 Isosteres of Aspartic Acid and Glutamic Acid 49 3.3.3 Tethered -Amino Acids: Constraining the -Space53 3.4 Dipeptide Isosteres 59 3.4.1 -Amino Acids 63 3.5 Tripeptide Isosteres 67 3.6 Conclusion 68 References 69 4. Solid-Phase Synthesis and Combinatorial Approaches toPeptidomimetics 75 4.1 Introduction 75 4.2 Solid-Phase Synthesis of Peptidomimetics 76 4.2.1 Scaffolds from -Amino Acids 76 4.2.2 Scaffolds from Amino Aldehyde Intermediates 85 4.2.3 Pyrrolidine-Containing Scaffolds 89 4.3 Conclusion 94 References 95 5. Click Chemistry: The Triazole Ring as a PrivilegedPeptidomimetic Scaffold 99 5.1 Introduction 99 5.1.1 CuAAC Reaction 100 5.1.2 Triazole Ring as a Peptidomimetic Isostere 101 5.2 Triazole-Containing Peptidomimetics Elaborated through Click Chemistry 102 5.2.1 Macrocycles 102 5.2.2 Oligomers and Foldamers 107 5.3 Relevant Applications in Drug Discovery 110 5.3.1 AChE Inhibitors 110 5.3.2 HIV Protease Inhibitors 111 5.3.3 MMP Inhibitors 114 5.3.4 Integrin Ligands 115 5.4 Conclusions 118 Acknowledgements 119 References 119 6. Peptoids 123 6.1 Introduction and Basics of Peptoids 123 6.2 Synthetic Methods 126 6.3 Macrocyclic Peptoids 129 6.4 Conformational Analysis of Folded Peptoids 130 6.5 Application of Peptoids as Antimicrobial Peptidomimetics132 6.6 Conclusions 134 References 134 7. Sugar Amino Acids 137 7.1 Introduction 137 7.2 -SAAs 138 7.2.1 Furanoid -SAAs 138 7.2.2 Pyranoid -SAAs 142 7.3 -SAAs 144 7.3.1 Furanoid -SAAs 144 7.3.2 Pyranoid -SAAs 147 7.4 -SAAs 148 7.5 -SAAs 150 7.5.1 Furanoid -SAAs 150 7.5.2 Pyranoid -SAAs 154 7.6 Representative Applications in Medicinal Chemistry 159 7.7 Conclusions 162 References 162 8. Cyclic -Amino Acids as Proline Mimetics 165 8.1 Introduction 165 8.2 Cyclic -Amino Acids 166 8.2.1 3-Substituted Proline Derivatives 167 8.2.2 4-Substituted Proline Derivatives 168 8.2.3 5-Substituted Proline Derivatives 169 8.2.4 Other Heterocyclic Proline Analogues 171 8.3 Bicyclic -Amino Acids 174 8.3.1 / -Ring Junction 175 8.3.2 / -Ring Junction 178 8.3.3 / -Ring Junction 179 8.3.4 / -Ring Junction 180 8.3.5 / -Ring Junction 182 8.3.6 N/ -Ring Junction 183 8.3.7 Pipecolic-Based Bicyclic -Amino Acids 183 8.3.8 Morpholine-Based Bicyclic -Amino Acids 187 8.4 Conclusions 189 References 189 9. -Turn Peptidomimetics 191 9.1 Introduction 191 9.2 Definition and Classification of -Turns 192 9.3 Conformational Analysis 194 9.4 -Turn Peptidomimetics 196 9.4.1 Proline Analogues in -Turn Peptidomimetics 197 9.4.2 -Amino Acids as Reverse-Turn Inducers 200 9.4.3 Molecular Scaffolds as -Turn Peptidomimetics 209 9.5 Conclusions 214 References 215 10. Peptidomimetic Foldamers 219 10.1 Introduction 219 10.2 Classification 220 10.3 Peptoids 221 10.4 -Peptides: First Systematic Conformational Studies221 10.5 Hybrid Foldamers 226 10.6 From Structural to Functional Foldamers 227 10.6.1 Peptoids as Foldameric Antimicrobial Peptidomimetics227 10.6.2 Foldamers Targeting Bcl-xL Antiapoptotic Proteins 227 10.7 Conclusions 228 References 228 PART III Applications in Medicinal Chemistry 231 11. Case Study 1: Peptidomimetic HIV Protease Inhibitors233 11.1 Introduction 233 11.2 The HIV-1 Virus 233 11.2.1 HIV-1 Protease 234 11.3 Antiretroviral Therapy 238 11.4 Drug Resistance 239 11.4.1 Mechanisms of Resistance to Protease Inhibitors 239 11.5 HIV-1 Protease Inhibitors 240 11.5.1 Transition-State Analogues 240 11.5.2 Peptidomimetic Drugs 241 11.5.3 Next-Generation Cyclic Peptidomimetic Inhibitors 245 11.6 Conclusions 255 Acknowledgements 255 References 256 12. Case Study 2: Peptidomimetic Ligands for Integrin259 12.1 Introduction 259 12.2 Peptide-Based Peptidomimetic Integrin Ligands 262 12.3 Scaffold-Based Peptidomimetic Integrin Ligands 270 12.4 Conclusions 280 References 280 Index 283.
  • (source: Nielsen Book Data)
A peptidomimetic is a small protein-like chain designed to mimic a peptide with adjusted molecular properties such as enhanced stability or biological activity. It is a very powerful approach for the generation of small-molecule-based drugs as enzyme inhibitors or receptor ligands. Peptidomimetics in Organic and Medicinal Chemistry outlines the concepts and synthetic strategies underlying the building of bioactive compounds of a peptidomimetic nature. Topics covered include the chemistry of unnatural amino acids, peptide- and scaffold-based peptidomimetics, amino acid-side chain isosteres, backbone isosteres, dipeptide isosteres, beta-turn peptidomimetics, proline-mimetics as turn inducers, cyclic scaffolds, amino acid surrogates, and scaffolds for combinatorial chemistry of peptidomimetics. Case studies in the hit-to-lead process, such as the development of integrin ligands and thrombin inhibitors, illustrate the successful application of peptidomimetics in drug discovery.
(source: Nielsen Book Data)
  • Preface xiii Abbreviations xvii PART I The Basics of Peptidomimetics 1 1. The Basics of Peptidomimetics 3 1.1 Introduction 3 1.2 Definition and Classification 5 1.3 Strategic Approaches to Peptidomimetic Design 7 1.3.1 Modification of Amino Acids 8 1.3.2 Compounds with Global Restrictions 9 1.3.3 Molecular Scaffolds Mimicking the Peptidic Backbone 10 1.4 Successful Examples of Peptidomimetic Drugs 12 1.4.1 ACE Inhibitors 13 1.4.2 Thrombin Inhibitors 13 1.5 Conclusion 16 References 16 2. Synthetic Approaches towards Peptidomimetic Design19 2.1 Introduction 19 2.2 Local Modifications 20 2.2.1 Single Amino Acid Modifications 23 2.2.2 Dipeptide Isosteres 26 2.2.3 Retro-inverso Peptides 29 2.2.4 N-Methylation of Peptides 30 2.2.5 Azapeptides 31 2.2.6 Peptoids 31 2.3 Global Restrictions through Cyclic Peptidomimetics 32 2.4 Peptidomimetic Scaffolds 34 2.5 Conclusions 35 References 35 PART II Synthetic Methods and Molecules 37 3. Peptidomimetic Bioisosteres 39 3.1 Introduction 39 3.2 Peptide Bond Isosteres 40 3.2.1 Thioamides 41 3.2.2 Esters 41 3.2.3 Alkenes and Fluoroalkenes 41 3.2.4 Transition-State Isosteres 42 3.3 Side-Chain Isosteres 45 3.3.1 Guanidine Isosteres in Arginine Peptidomimetics 45 3.3.2 Isosteres of Aspartic Acid and Glutamic Acid 49 3.3.3 Tethered -Amino Acids: Constraining the -Space53 3.4 Dipeptide Isosteres 59 3.4.1 -Amino Acids 63 3.5 Tripeptide Isosteres 67 3.6 Conclusion 68 References 69 4. Solid-Phase Synthesis and Combinatorial Approaches toPeptidomimetics 75 4.1 Introduction 75 4.2 Solid-Phase Synthesis of Peptidomimetics 76 4.2.1 Scaffolds from -Amino Acids 76 4.2.2 Scaffolds from Amino Aldehyde Intermediates 85 4.2.3 Pyrrolidine-Containing Scaffolds 89 4.3 Conclusion 94 References 95 5. Click Chemistry: The Triazole Ring as a PrivilegedPeptidomimetic Scaffold 99 5.1 Introduction 99 5.1.1 CuAAC Reaction 100 5.1.2 Triazole Ring as a Peptidomimetic Isostere 101 5.2 Triazole-Containing Peptidomimetics Elaborated through Click Chemistry 102 5.2.1 Macrocycles 102 5.2.2 Oligomers and Foldamers 107 5.3 Relevant Applications in Drug Discovery 110 5.3.1 AChE Inhibitors 110 5.3.2 HIV Protease Inhibitors 111 5.3.3 MMP Inhibitors 114 5.3.4 Integrin Ligands 115 5.4 Conclusions 118 Acknowledgements 119 References 119 6. Peptoids 123 6.1 Introduction and Basics of Peptoids 123 6.2 Synthetic Methods 126 6.3 Macrocyclic Peptoids 129 6.4 Conformational Analysis of Folded Peptoids 130 6.5 Application of Peptoids as Antimicrobial Peptidomimetics132 6.6 Conclusions 134 References 134 7. Sugar Amino Acids 137 7.1 Introduction 137 7.2 -SAAs 138 7.2.1 Furanoid -SAAs 138 7.2.2 Pyranoid -SAAs 142 7.3 -SAAs 144 7.3.1 Furanoid -SAAs 144 7.3.2 Pyranoid -SAAs 147 7.4 -SAAs 148 7.5 -SAAs 150 7.5.1 Furanoid -SAAs 150 7.5.2 Pyranoid -SAAs 154 7.6 Representative Applications in Medicinal Chemistry 159 7.7 Conclusions 162 References 162 8. Cyclic -Amino Acids as Proline Mimetics 165 8.1 Introduction 165 8.2 Cyclic -Amino Acids 166 8.2.1 3-Substituted Proline Derivatives 167 8.2.2 4-Substituted Proline Derivatives 168 8.2.3 5-Substituted Proline Derivatives 169 8.2.4 Other Heterocyclic Proline Analogues 171 8.3 Bicyclic -Amino Acids 174 8.3.1 / -Ring Junction 175 8.3.2 / -Ring Junction 178 8.3.3 / -Ring Junction 179 8.3.4 / -Ring Junction 180 8.3.5 / -Ring Junction 182 8.3.6 N/ -Ring Junction 183 8.3.7 Pipecolic-Based Bicyclic -Amino Acids 183 8.3.8 Morpholine-Based Bicyclic -Amino Acids 187 8.4 Conclusions 189 References 189 9. -Turn Peptidomimetics 191 9.1 Introduction 191 9.2 Definition and Classification of -Turns 192 9.3 Conformational Analysis 194 9.4 -Turn Peptidomimetics 196 9.4.1 Proline Analogues in -Turn Peptidomimetics 197 9.4.2 -Amino Acids as Reverse-Turn Inducers 200 9.4.3 Molecular Scaffolds as -Turn Peptidomimetics 209 9.5 Conclusions 214 References 215 10. Peptidomimetic Foldamers 219 10.1 Introduction 219 10.2 Classification 220 10.3 Peptoids 221 10.4 -Peptides: First Systematic Conformational Studies221 10.5 Hybrid Foldamers 226 10.6 From Structural to Functional Foldamers 227 10.6.1 Peptoids as Foldameric Antimicrobial Peptidomimetics227 10.6.2 Foldamers Targeting Bcl-xL Antiapoptotic Proteins 227 10.7 Conclusions 228 References 228 PART III Applications in Medicinal Chemistry 231 11. Case Study 1: Peptidomimetic HIV Protease Inhibitors233 11.1 Introduction 233 11.2 The HIV-1 Virus 233 11.2.1 HIV-1 Protease 234 11.3 Antiretroviral Therapy 238 11.4 Drug Resistance 239 11.4.1 Mechanisms of Resistance to Protease Inhibitors 239 11.5 HIV-1 Protease Inhibitors 240 11.5.1 Transition-State Analogues 240 11.5.2 Peptidomimetic Drugs 241 11.5.3 Next-Generation Cyclic Peptidomimetic Inhibitors 245 11.6 Conclusions 255 Acknowledgements 255 References 256 12. Case Study 2: Peptidomimetic Ligands for Integrin259 12.1 Introduction 259 12.2 Peptide-Based Peptidomimetic Integrin Ligands 262 12.3 Scaffold-Based Peptidomimetic Integrin Ligands 270 12.4 Conclusions 280 References 280 Index 283.
  • (source: Nielsen Book Data)
A peptidomimetic is a small protein-like chain designed to mimic a peptide with adjusted molecular properties such as enhanced stability or biological activity. It is a very powerful approach for the generation of small-molecule-based drugs as enzyme inhibitors or receptor ligands. Peptidomimetics in Organic and Medicinal Chemistry outlines the concepts and synthetic strategies underlying the building of bioactive compounds of a peptidomimetic nature. Topics covered include the chemistry of unnatural amino acids, peptide- and scaffold-based peptidomimetics, amino acid-side chain isosteres, backbone isosteres, dipeptide isosteres, beta-turn peptidomimetics, proline-mimetics as turn inducers, cyclic scaffolds, amino acid surrogates, and scaffolds for combinatorial chemistry of peptidomimetics. Case studies in the hit-to-lead process, such as the development of integrin ligands and thrombin inhibitors, illustrate the successful application of peptidomimetics in drug discovery.
(source: Nielsen Book Data)

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