Real World Drug Discovery A Chemist’s Guide to Biotech and Pharmaceutical Research 1st Edition by Robert Rydzewski 0080914888 9780080914886

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Product details:

ISBN 10: 0080914888 

ISBN 13: 9780080914886

Author: Robert M. Rydzewski

Drug discovery increasingly requires a common understanding by researchers of the many and diverse factors that go into the making of new medicines. The scientist entering the field will immediately face important issues for which his education may not have prepared him: project teams, patent law, consultants, target product profiles, industry trends, Gantt charts, target validation, pharmacokinetics, proteomics, phenotype assays, biomarkers, and many other unfamiliar topics for which a basic understanding must somehow be obtained. Even the more experienced scientist can find it frustratingly difficult to get an overview of the many factors involved in modern drug discovery and often only after years of exploring does a whole and integrated picture emerge in the mind of the researcher.

Real World Drug Discovery: A Chemist’s Guide to Biotech and Pharmaceutical Research presents this kind of map of the landscape of drug discovery. In a single, readable volume it outlines processes and explains essential concepts and terms for the recent science graduate wondering what to expect in pharma or biotech, the medicinal chemist seeking a broader and more timely understanding of the industry, or the contractor or collaborator whose understanding of the commercial drug discovery process could increase the value of his contribution to it.

Key Features:

– Interviews with well-known experts in many of the fields involved, giving insightful comments from authorities on many of the sub-disciplines important to cutting edge drug discovery.

– Helpful suggestions gleaned from years of experience in biotech and pharma, which represents a repository drug discovery “lore” not previously available in any book.

– “Periodic Table of Drugs” listing current top-selling drugs arranged by target and laid out so that structural similarities and differences are plain and clear, with regular updates available at the book’s website.

– Extensive use of diagrams to illustrate concepts like biotech startup models, preteomic profiling for target identification, Gantt charts for project planning, etc.

Table of contents:

Chapter 1 The Drug Discovery Business to Date
1.1 Introduction
1.2 The Past
1.2.1 Pharma Roots
1.2.2 Biotech is Born
1.2.3 The Genomics Revolution
1.3 Current Economics—Problems
1.3.1 Cost of Drug Development
1.3.2 The Productivity Gap
1.3.3 Market Withdrawals
1.3.4 Generic Competition
1.4 Current Economics—Solutions
1.4.1 Pharma Profits and Market Expansion
1.4.2 Mergers and Acquisitions
1.4.3 Biotech Clinical Candidates to Pharma
1.4.4 Academic Contributions
1.4.5 Global Outsourcing
1.4.6 Blockbusters and Orphan Drugs
1.4.7 Repurposing
1.4.8 Chiral Switching
1.4.9 Combination Therapeutics
1.4.10 Reformulation
1.5 Summary

Chapter 2 The Drug Discovery Business to Come
2.1 Introduction
2.2 New Models for Pharma
2.2.1 R&D Minus R
2.2.2 D Plus R
2.2.3 Smaller is Better
2.2.4 Specialty Drugs
2.2.5 Pricing Pressures and Price Controls
2.3 New Models for Academia and Biotech
2.3.1 Translational Research
2.3.2 The Standard Biotech Model
2.3.3 “Is it a project or a company?”
2.3.4 Leaner, Meaner Start-ups
2.3.5 Biotech Alternatives
2.4 New Technologies
2.4.1 S-Curves and Expectations
2.4.2 Genomics Redux
2.4.3 Personalized Medicine
2.4.4 Pharmacogenomics
2.4.5 Other “Omics”
2.4.6 The Adoption of Personalized Medicine
2.5 Summary

Chapter 3 Industrial Considerations
3.1 Intellectual Property
3.1.1 The Value of New Ideas
3.1.2 Patents
3.2 Outside Resources
3.2.1 Consultants
3.2.2 Academic or Government Research Agreements
3.2.3 Big Company–Small Company Collaborations
3.3 The New Drug R&D Process
3.3.1 Target Identification
3.3.2 Lead Identification
3.3.3 Lead Optimization
3.3.4 Preclinical
3.3.5 Stages in Clinical Development
3.3.6 What are the Odds?

Chapter 4 How Things Get Done: The Project Team
4.1 Introduction
4.2 The Project Team
4.2.1 The Project Goal
4.2.2 Project Team Organization
4.2.3 Project Team Meetings
4.3 Conclusions
4.3.1 Summing Up…
4.3.2 Is it Really Best?
4.3.3 The Benefits

Chapter 5 Project Considerations
5.1 Introduction
5.2 Established Targets
5.3 Established “Tough Targets”
5.4 Novel Targets
5.4.1 Identifying New Targets
5.4.2 Target Validation
5.4.3 Working on Novel Target-Directed Projects
5.5 Targets Arising from Phenotype or High-Content Screening
5.5.1 Phenotype Screening Versus Target Screening
5.5.2 Elucidation of Phenotype-Derived Targets
5.6 In Conclusion

Chapter 6 Hit Generation
6.1 Introduction
6.2 Definitions
6.3 Groups Involved in Hit-to-Lead
6.4 High-Throughput Screening
6.4.1 History
6.4.2 Myths and Truths about HTS
6.5 Approaches to Hit Generation
6.5.1 Random or Non-Directed Methods
6.5.2 Screening of Synthetic Compound Collections
6.5.3 Screening of Combinatorial Diversity Libraries
6.5.4 Fragment Screening
6.5.5 Screening of Natural Products and DOS Libraries
6.5.6 Directed or Knowledge-Based Methods

Chapter 7 Turning Hits into Drugs
7.1 What Now?
7.2 Biochemical Mechanism in Hit Selection
7.2.1 Competition and Allostery
7.2.2 Irreversibility
7.2.3 Slow Off-Rate Compounds
7.2.4 Why Mechanism Matters
7.3 Druglikeness
7.3.1 What is It?
7.3.2 Predicting Druglikeness
7.4 Multidimensional Optimization
7.5 Lead Optimization Versus HTL
7.6 Using Structure-Based Drug Design
7.6.1 Definition, History, and Goals
7.6.2 Potential Limitations
7.6.3 Examples
7.6.4 Working with Modelers
7.6.5 Conclusions

Chapter 8 Initial Properties
8.1 Why Not All At Once?
8.2 Potency
8.2.1 What, Why, and How Much?
8.2.2 Species Specificity
8.3 Selectivity
8.3.1 Selectivity … Not!
8.3.2 Antitargets
8.4 Structural Novelty
8.4.1 Bioisosteres, Group, and Atom Replacements
8.4.2 Scaffold Hopping, Morphing, and Grafting
8.4.3 Cyclization and Ring Opening
8.4.4 Other Methods
8.5 Solubility
8.5.1 Defining, Estimating, and Measuring Solubility
8.5.2 Problems Resulting from Poor Solubility
8.5.3 Improving Solubility
8.6 Chemical and Plasma Stability
8.6.1 Definitions and Importance
8.6.2 Common Types of Instability

Chapter 9 ADME and PK Properties
9.1 Cell Permeability and Absorption
9.1.1 Definitions
9.1.2 A Closer Look at Intestinal Absorption
9.1.3 Models of Cell Permeability and Absorption
9.1.4 Improving Cell Permeability and Absorption
9.2 Metabolic Stability
9.2.1 Common Metabolic Transformations
9.2.2 Assessing Metabolic Stability
9.2.3 Improving Metabolic Stability
9.3 Plasma Protein Binding
9.3.1 Is It Important?
9.3.2 Measuring Plasma Protein Binding
9.3.3 Minimizing Plasma Protein Binding
9.4 P-Glycoprotein Interactions
9.4.1 Structure and Function
9.4.2 Types of P-gp Interactions
9.4.3 Measuring P-gp Interactions
9.4.4 Reducing P-gp Interactions
9.5 Bioavailability
9.5.1 Introduction
9.5.2 Understanding and Overcoming Poor Oral Bioavailability
9.5.3 Things to Keep in Mind

Chapter 10 Toxicity-Related Properties
10.1 CYP Inhibition
10.1.1 Importance
10.1.2 Types of CYP Inhibition
10.1.3 CYP Inhibition Assays
10.1.4 Common Structural Features of CYP Inhibitors
10.1.5 Ways to Reduce CYP Inhibition
10.2 CYP Induction
10.3 Binding to the hERG receptor
10.3.1 Introduction
10.3.2 In Vitro Assays
10.3.3 Models of hERG binding
10.3.4 Reducing hERG Interactions
10.4 Mutagenicity
10.4.1 Background
10.4.2 Structural Aspects

Chapter 11 A Career in Drug Discovery Research
11.1 Hiring: A Good Match
11.1.1 What Do Employers Want?
11.1.2 What Should a Candidate Look For?
11.2 Assessing Performance
11.2.1 Evaluations
11.2.2 Promotions
11.3 The Long Haul: Perspectives
11.3.1 Job and Industry Evolution
11.3.2 The Evolution of a Research Career
11.3.3 Frustration
11.3.4 Hope

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Tags: Robert Rydzewski, Discovery, Chemist’s, Pharmaceutical