Daniel L. Young, Seth Michelson

Systems Biology in Drug Discovery and Development (eBook, PDF)

• Format: PDF

Produktbeschreibung

The first book to focus on comprehensive systems biology as applied to drug discovery and development Drawing on real-life examples, Systems Biology in Drug Discovery and Development presents practical applications of systems biology to the multiple phases of drug discovery and development. This book explains how the integration of knowledge from multiple sources, and the models that best represent that integration, inform the drug research processes that are most relevant to the pharmaceutical and biotechnology industries. The first book to focus on comprehensive systems biology and its applications in drug discovery and development, it offers comprehensive and multidisciplinary coverage of all phases of discovery and design, including target identification and validation, lead identification and optimization, and clinical trial design and execution, as well as the complementary systems approaches that make these processes more efficient. It also provides models for applying systems biology to pharmacokinetics, pharmacodynamics, and candidate biomarker identification. Introducing and explaining key methods and technical approaches to the use of comprehensive systems biology on drug development, the book addresses the challenges currently facing the pharmaceutical industry. As a result, it is essential reading for pharmaceutical and biotech scientists, pharmacologists, computational modelers, bioinformaticians, and graduate students in systems biology, pharmaceutical science, and other related fields.

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Produktdetails

• Verlag: John Wiley & Sons
• Seitenzahl: 376
• Erscheinungstermin: 9. September 2011
• Englisch
• ISBN-13: 9781118016411
• Artikelnr.: 38242113

Autorenporträt

Daniel L. Young, PhD the Director of Computational Biosciences at Theranos Inc., where he leads the development of systems biology approaches to advance and enhance drug discovery and development and the optimal delivery of healthcare. He has written over twenty publications in the field of systems biology. Seth Michelson, PhD, is the Director of Nonclinical Biostatistics at Genomic Health, Inc. inventor or co-inventor for fourteen patent applications and one issued patent; and has contributed to over seventy publications.

Inhaltsangabe

Part I: Introduction to Systems Biology Approach. Chapter 1. Introduction
to systems biology in drug discovery and development. 1.1 Introduction.
Chapter 2. Methods for In Silico Biology: Model Construction and Analysis.
2.1 Introduction. 2.2 Model building. 2.3 Parameter estimation. 2.4. Model
analysis. 2.5 Conclusions. Chapter 3. Methods in In Silico Biology:
Modeling Feedback Dynamics in Pathways. 3.1 Introduction. 3.2 Statistical
modeling. 3.3 Mathematical modeling. 3.4 Feedback and feedforward. 3.5
Conclusions. Chapter 4. Simulation of Population Variability in
Pharmacokinetics. 4.1 Introduction. 4.2 PBPK modeling. 4.3 Simulation of
pharmacokinetic variability. 4.4 Conclusions and future directions. Part
II: Applications to Drug Discovery. Chapter 5. Applications of Systems
Biology Approaches to Target Identification and Validation in Drug
Discovery. 5.1 Introduction. 5.2 Typical drug discovery paradigm. 5.3
Integrated drug discovery. 5.4 Drivers of the disease phenotype: clinical
endpoints and hypotheses. 5.5 Extracellular disease drivers: mechanistic
biotherapeutic models. 5.6 Relevant cell models for clinical endpoints. 5.7
Intracellular disease drivers: signaling pathway quantification. 5.8 Target
selection: dynamic pathway modeling. 5.9 Conclusions. Chapter 6. Lead
Identification and Optimization. 6.1 Introduction. 6.2 The systems biology
toolkit. 6.3 Conclusions. Chapter 7. The role of core biological motifs in
dose-response modeling: an example with switch-like circuits. 7.1
Introduction: systems perspective in drug discovery. 7.2 Systems biology
and toxicology. 7.3 Mechanistic/computational concepts in a
molecular/cellular context. 7.4 Response motifs in cell signaling and their
role in dose response. 7.5 Discussion and conclusions. Chapter 8. Mechanism
Based Pharmacokinetic-Pharmacodynamic Modeling During Discovery and Early
Development. 8.1 Introduction. 8.2 Challenges in drug discovery and
development: the need to bring together PK and PD. 8.3 Methodological
aspects and concepts. 8.4 Application during lead optimization. 8.5
Application during clinical candidate selection. 8.6 Entry into human (EIH)
preparation and translational PK/PD modeling. 8.7 PK/PD for toxicology
study design and evaluation. 8.8 Justification of starting dose,
calculation of safety margins, and support of phase I design. 8.9 Phase I
and beyond. 8.10 Support of early formulation development. 8.11 Outlook and
conclusions. Part III: Applications to Drug Development. Chapter 9.
Developing Oncology Drugs Using Virtual Patients of Vascular Tumor
Diseases. 9.1 Introduction. 9.2 Modeling angiogenesis. 9.3 Use of rigorous
mathematical analysis for gaining insight on drug development. 9.4 Use of
angiogenesis models in theranostics. 9.5 Use of angiogenesis models in drug
salvage: the virtual patient technology. 9.6 Summary and conclusions.
Chapter 10. Systems Modeling Applied to Candidate Biomarker Identification.
10.1 Introduction. 10.2 Biomarker discovery approaches. 10.3 Examples of
systems modeling approaches for identification of candidate biomarkers.
10.4 Conclusions. Chapter 11. Simulating Clinical Trials. 11.1
Introduction. 11.2 Types of models used in clinical trial design. 11.3
Sources of prior information for designing clinical trials. 11.4 Aspects of
a trial to be designed and optimized. 11.5 Trial simulation. 11.6
Optimizing designs. 11.7 Real world examples. 11.8 Conclusions. Part IV:
Synergies with other technologies. Chapter 12. Pathway Analysis in Drug
Discovery. 12.1 Introduction: pathway analysis, dynamic modeling, and
network analysis. 12.2 Software systems for pathway analysis. 12.3 Pathway
analysis in modern drug development pipeline. 12.4 Conclusions. Chapter 13.
Functional mapping for predicting drug response and enabling personalized
medicine. 13.1 Introduction. 13.2 Functional mapping. 13.3 Predictive
modeling. 13.4 Future directions. Chapter 14. Future Outlook of Systems
Biology. 14.1 Introduction. 14.2 Systems complexity in biological systems.
14.3 Models for quantitative integration of data. 14.4 Changing
requirements for systems approaches during drug discovery and development.
14.5 Better models for better decisions. 14.6 Advancing personalized
medicine. 14.7 Improving clinical trials and enabling more complex
treatment approaches. 14.8 Collaboration and training for systems
biologists. 14.9 Conclusions.