𝔖 Scriptorium
✦   LIBER   ✦

📁

Basic Principles of Drug Discovery and Development

✍ Scribed by Benjamin E. Blass


Publisher
Academic Press
Year
2021
Tongue
English
Leaves
725
Edition
2
Category
Library

⬇  Acquire This Volume

No coin nor oath required. For personal study only.

✦ Synopsis


Basic Principles of Drug Discovery and Development presents the multifaceted process of identifying a new drug in the modern era, which requires a multidisciplinary team approach with input from medicinal chemists, biologists, pharmacologists, drug metabolism experts, toxicologists, clinicians, and a host of experts from numerous additional fields. Enabling technologies such as high throughput screening, structure-based drug design, molecular modeling, pharmaceutical profiling, and translational medicine are critical to the successful development of marketable therapeutics.

Given the wide range of disciplines and techniques that are required for cutting edge drug discovery and development, a scientist must master their own fields as well as have a fundamental understanding of their collaborator’s fields. This book bridges the knowledge gaps that invariably lead to communication issues in a new scientist’s early career, providing a fundamental understanding of the various techniques and disciplines required for the multifaceted endeavor of drug research and development. It provides students, new industrial scientists, and academics with a basic understanding of the drug discovery and development process. The fully updated text provides an excellent overview of the process and includes chapters on important drug targets by class, in vitro screening methods, medicinal chemistry strategies in drug design, principles of in vivo pharmacokinetics and pharmacodynamics, animal models of disease states, clinical trial basics, and selected business aspects of the drug discovery process.

✦ Table of Contents


Title-page_2021_Basic-Principles-of-Drug-Discovery-and-Development
Basic Principles of Drug Discovery and Development
Copyright_2021_Basic-Principles-of-Drug-Discovery-and-Development
Copyright
Dedication_2021_Basic-Principles-of-Drug-Discovery-and-Development
Dedication
Contents_2021_Basic-Principles-of-Drug-Discovery-and-Development
Contents
Foreword_2021_Basic-Principles-of-Drug-Discovery-and-Development
Foreword
Chapter-1---Drug-discovery-and-development--A_2021_Basic-Principles-of-Drug-
1 Drug discovery and development: An overview of modern methods and principles
Drug discovery and development from 20,000Feet (Fig. 1.9)
Target selection: the first step forward
Hit identification: finding a starting point
Identify a clinical candidate: juggling the properties
Questions
References
Chapter-2---The-drug-discovery-process--Fro_2021_Basic-Principles-of-Drug-Di
2 The drug discovery process: From ancient times to the present day
The age of botanicals: pre-industrial drug discovery
Early biotherapeutics: before the biotechnology revolution
Paul Ehrlich: the father of modern drug discovery
Milestones in drug discovery
Milestones in animal models: breeding a better model
The Wistar rat
Immunocompromised mice
The nude mouse34
The SCID mouse
Transgenic animal models
Knockout animal models
Milestones in molecular science
X-ray crystallography
Molecular modeling and computational chemistry
High-throughput technology: chemical synthesis and screening science
Milestones in biotechnology
Recombinant DNA and transfection technology
Polymerase chain reaction technology
DNA Sequencing and genomics
Proteomics
Monoclonal antibody and hybridoma technology
The rise of biologics and macromolecular therapeutics
Societal and governmental impacts
The Pure Food and Drug Act of 1906180
The Elixir of Sulfanilamide Disaster of 1937184
The Thalidomide story186
Regulatory milestones
Durham-Humphrey Amendment of 1951187
Kefauver-Harris Amendment of 1962188
Hatch-Waxman Act of 1984189
Biologics Price Competition and Innovation Act of 2009190
Future developments in drug discovery
Questions
References
Chapter-3---Classical-targets-in-d_2021_Basic-Principles-of-Drug-Discovery-a
3 Classical targets in drug discovery
Protein structure
Enzymes
Inhibition of enzymes
G-protein-coupled receptors
G-protein-dependent signaling pathways
Cyclic adenosine monophosphate signaling
IP3 signaling
β-Arrestin pathways
G-protein-coupled receptor signaling pathways
Modulating G-protein-coupled receptor signaling
Ion channels
Gating mechanisms
Ligand-gated channels
Voltage-gated channels
Other gating mechanisms
Membrane transport proteins (transporters)
Nuclear receptors
Nuclear receptor signaling pathways
Modulating nuclear receptor activity
Biomolecular interactions: protein/protein, protein/DNA, and protein/RNA interfaces
Types of “hot spots” in biomolecular interactions
Stabilizing biomolecular interactions
Questions
References
Chapter-4---In-vitro-screening-_2021_Basic-Principles-of-Drug-Discovery-and-
4 In vitro screening systems
The language of screening: basic terms
Concentration–response curves and IC50s
Dissociation constants (Kd) and inhibition constants (Ki)
Efficacy versus binding: EC50s
Agonist, partial agonist, antagonist, allosteric modulators, and inverse agonists
Agonists and partial agonists
Antagonists
Basal activity and inverse agonist
Receptor reserve
Allosteric modulation
Streptavidin and biotin
Biochemical versus cellular assays
Assay systems and methods of detection
Radioligand systems
Scintillation proximity assay
Enzyme-linked immunosorbent assay
Fluorescence-based assay systems
Fluorescence polarization
Fluorescence resonance energy transfer
Time-resolved fluorescence resonance energy transfer
Amplified luminescent proximity homogeneous assay (AlphaScreen™)
Fluorescent detection of calcium flux
Reporter gene assays
Chloramphenicol acetyltransferase
β-Lactamase reporter assays
Luciferase reporter assays
Bioluminescence resonance energy transfer assays
Kinetic fluorescent measurement systems
Label-free assay systems
Cellular dielectric spectroscopy
Optical biosensors
Surface plasmon resonance technology
Electrophysiological patch clamp
Thermal shift assay
High content screening
General consideration for all screening methods
Questions
References
Chapter-5---Medicinal-chemi_2021_Basic-Principles-of-Drug-Discovery-and-Deve
5 Medicinal chemistry
Structure–activity relationships and structure–property relationships
The role of chirality
Push and pull in structure–activity relationships
Quantitative structure–activity relationships
The pharmacophore
Developing an structure–activity relationship data set
The structure–activity relationship cycle
Bioisosterism
Structure–activity relationship, selectivity, and physicochemical properties
“Drug-like” guidelines
Questions
References
Chapter-6---In-vitro-ADME-and-in-vivo_2021_Basic-Principles-of-Drug-Discover
6 In vitro ADME and in vivo pharmacokinetics
Absorption
Solubility
Permeability
Distribution
Permeability
Transporters
Plasma protein binding
Elimination pathways
Metabolism
Excretion
In vitro ADME model systems
In Vivo pharmacokinetics
Volume of distribution
Clearance
Half-life
Bioavailability
Species selection
Questions
References
Chapter-7---Animal-models-of-dise_2021_Basic-Principles-of-Drug-Discovery-an
7 Animal models of disease states
Sources of animal models
Validity of animal models
Species selection
Number of animals
Exemplary animal models by disease category
Animal models in neuroscience
The forced swimming test: A model of depression19
The elevated plus maze: A measure of anxiety20
The novel object recognition test: A model of memory and cognition21
Contextual fear conditioning model: A model of contextual learning22
The Morris water maze: A model of spatial learning and memory23
Animal models of neurodegeneration
The SOD1G93A mouse of amyotrophic lateral sclerosis (ALS)24
The MPTP model of Parkinson’s disease25
Animal models of cardiovascular disease
Models of hypertension
Models of hyperlipidemia and high cholesterol
Models of atrial fibrillation
Models of heart failure
Animal models of infectious disease
Murine thigh infection model
Murine model of systemic infection
Mouse model of influenza virus infection
Limitations of animal models of infection
Animal models of oncology
Mouse xenograft tumor model
Mouse allograft tumor model
Genetically engineered mouse models of cancer
Animal models of pain
The Von Frey test
The Ramdall-Selitto test
Heat based models
Inflammation based models
Surgical models
General consideration for pain models
Animal models of diabetes
Animal models of drug addiction
Conclusion
Questions
References
Chapter-8---Safety-and-toxic_2021_Basic-Principles-of-Drug-Discovery-and-Dev
8 Safety and toxicology
Sources of toxicity
Acute versus chronic toxicity
Cytotoxicity
Carcinogenicity, genotoxicity, and mutagenicity
Drug–drug interactions
Cardiovascular safety and toxicology studies
Central nervous system safety and toxicology studies
Immune system-mediated safety issues
Teratogenicity
In vivo toxicity and safety studies
Questions
References
Chapter-9---Antibody-drug-dis_2021_Basic-Principles-of-Drug-Discovery-and-De
9 Antibody-drug discovery
IgG structure and function
Antibody therapy drug discovery
Hybridoma technology
Antibody phage display
Modified monoclonal antibodies
General considerations
Conclusion
Questions
References
Chapter-10---Basics-of-clinical_2021_Basic-Principles-of-Drug-Discovery-and-
10 Basics of clinical trials
Before the clinic
Drug supply
Delivery methods
Formulation
Investigational new drug application
Phase 1 clinical trials
Phase 2 clinical trials
Phase 3 clinical trials
Phase 4 clinical trials
Adaptive clinical trial design59
Meta-analysis of clinical trial data
Questions
References
Chapter-11---Translational-medicine_2021_Basic-Principles-of-Drug-Discovery-
11 Translational medicine and biomarkers
Definition of a biomarker and their classification
Characteristics and impact of biomarkers
Biomarkers versus surrogate endpoints
Imaging technologies
The practical application of biomarkers
Dipeptidyl peptidase IV inhibitors (Januvia)
Physiological measurements as biomarkers: Orexin antagonists
FDG PET imaging agent
The neurokinin 1 receptor, depression, and PET imaging: The Aprepitant story
Cancer biomarkers
Conclusion
Questions
References
Chapter-12---Organizational-consideration-an_2021_Basic-Principles-of-Drug-D
12 Organizational consideration and trends in the pharmaceutical industry
Organizational structures of pharmaceutical companies
Business divisions interactions
The discovery project team evolutionary cycle
The business climate
Mergers and acquisitions
Contract research organizations
Academic drug discovery
Funding issues
Conclusion
Questions
Appendix 1
References
Chapter-13---Intellectual-property-and-p_2021_Basic-Principles-of-Drug-Disco
13 Intellectual property and patents in drug discovery
Patentable subject matter
Inherent properties and patentability
Novelty and the prior art
Obviousness and the prior art
Inventorship
Assignment and ownership
Classification of patents and patent applications
Impact of overlapping patents
Patent applications and their contents
Contents of a patent application
Conclusion
Questions
References
Chapter-14---Case-studies-in-drug_2021_Basic-Principles-of-Drug-Discovery-an
14 Case studies in drug discovery
Tamiflu: From mechanism of action to marketed drug
Histone deacylase inhibitors: Physicochemical optimization via structural change
HIV protease inhibitors: Chemically complex miracle drugs
Nitrofurantoin: A surprisingly successful drug
Seldane® (Terfenadine) vs Allegra® (Fexofenadine): Metabolism matters: Safety
Claritin® (Loratadine) versus Clarinex® (Desloratadine): Metabolism matters: Pharmacokinetics
MPTP: Parkinson’s disease in a bottle
Bupropion and Methylphenidate: Improving performance via formulation changes
Selective inhibition of COX-2: The impact of an inadequate written description
Antibiotic resistant bacteria and the development of β-lactamase inhibitors
Association for Molecular Pathology vs Myriad Genetics: The validity of gene patents
Conclusion
Questions
References
Answers-to-questions-in-textbook-_2021_Basic-Principles-of-Drug-Discovery-an
Answers to questions in textbook by chapter
Chapter 1
Chapter 2
Chapter 3
Chapter 4
Chapter 5
Chapter 6
Chapter 7
Chapter 8
Chapter 9
Chapter 10
Chapter 11
Chapter 12
Chapter 13
Chapter 14
Subject-Index_2021_Basic-Principles-of-Drug-Discovery-and-Development
Subject Index
Drug-Index_2021_Basic-Principles-of-Drug-Discovery-and-Development
Drug Index


📜 SIMILAR VOLUMES


Basic Principles of Drug Discovery and D
✍ Benjamin E. Blass 📂 Library 📅 2015 🏛 Academic Press 🌐 English

<p><i>Basic Principles of Drug Discovery and Development</i> presents the multifaceted process of identifying a new drug in the modern era, providing comprehensive explanations of enabling technologies such as high throughput screening, structure based drug design, molecular modeling, pharmaceutical

Basic Principles of Drug Discovery and D
✍ Benjamin Blass 📂 Library 📅 2015 🏛 Academic Press 🌐 English

<p><i>Basic Principles of Drug Discovery and Development</i> presents the multifaceted process of identifying a new drug in the modern era, providing comprehensive explanations of enabling technologies such as high throughput screening, structure based drug design, molecular modeling, pharmaceutical

Oral Bioavailability: Basic Principles,
✍ Xiaoling Li, Ming Hu 📂 Library 📅 2011 🏛 Wiley 🌐 English

<p>Understand and assess the design, delivery, and efficacy of orally administered drugs <p>A practical guide to understanding oral bioavailability, one of the major hurdles in drug development and delivery, Oral Bioavailability: Basic Principles, Advanced Concepts, and Applications is designed to h

Drug Delivery: Principles and Applicatio
✍ Binghe Wang, Teruna J. Siahaan, Richard A. Soltero 📂 Library 📅 2005 🏛 Wiley-Interscience 🌐 English

An indispensable tool for those working at the front lines of new drug developmentWritten for busy professionals at the forefront of new drug development, Drug Delivery gets readers quickly up to speed on both the principles and latest applications in the increasingly important field of drug deliver

Carbon Monoxide in Drug Discovery: Basic
✍ Leo E. Otterbein (editor), Binghe Wang (editor) 📂 Library 📅 2022 🏛 Wiley 🌐 English

<span>CARBON MONOXIDE IN DRUG DISCOVERY</span><p><span>An insightful reference for the latest physiological and therapeutic studies of carbon monoxide</span></p><p><span>In </span><span>Carbon Monoxide in Drug Discovery: Basics, Pharmacology, and Therapeutic Potential,</span><span> a team of disting

Oral Bioavailability Assessment: Basics
✍ Ayman F. El-Kattan, Mike S. Lee 📂 Library 📅 2017 🏛 Wiley 🌐 English

Specifically geared to personnel in the pharmaceutical and biotechnology industries, this book describes the basics and challenges of oral bioavailability – one of the most significant hurdles in drug discovery and development.<br /><br />•    Describes approaches to assess pharmacokinetics and how