Predictive toxicology : from vision to reality

Author(s)

    • Pfannkuch, Friedlieb
    • Suter-Dick, Laura

Bibliographic Information

Predictive toxicology : from vision to reality

edited by Friedlieb Pfannkuch and Laura Suter-Dick

(Methods and principles in medicinal chemistry / edited by R. Mannhold ... [et al.], v. 64)

Wiley-VCH, c2015

Available at  / 2 libraries

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Note

Includes bibliographical references and index

Description and Table of Contents

Description

Tailored to the needs of scientists developing drugs, chemicals, cosmetics and other products this one-stop reference for medicinal chemists covers all the latest developments in the field of predictive toxicology and its applications in safety assessment. With a keen emphasis on novel approaches, the topics have been tackled by selected expert scientists, who are familiar with the theoretical scientific background as well as with the practical application of current methods. Emerging technologies in toxicity assessment are introduced and evaluated in terms of their predictive power, with separate sections on computer predictions and simulation methods, novel in vitro systems including those employing stem cells, toxicogenomics and novel biomarkers. In each case, the most promising methods are discussed and compared to classical in vitro and in vivo toxicology assays. Finally, an outlook section discusses such forward-looking topics as immunotoxicology assessment and novel regulatory requirements. With its wealth of methodological knowledge and its critical evaluation of modern approaches, this is a valuable guide for toxicologists working in pharmaceutical development, as well as in safety assessment and the regulation of drugs and chemicals.

Table of Contents

Preface INTRODUCTION TO PREDICTIVE TOXICOLOGY TOOLS AND METHODS Computational Tools and Bioinformatics Omics Technologies Data Interpretation and Knowledge Management Biomarker Development Advanced In Vitro Systems and Stem Cell Research Immunogenicity Integration and Validation Research Initiative/Collaborations Concluding Remarks IN SILICO TOXICOLOGY - CURRENT APPROACHES AND FUTURE PERSPECTIVES TO PREDICT TOXIC EFFECTS WITH COMPUTATIONAL TOOLS Introduction Prediction of Hazard Prediction of Risk Thoughts on Validation Conclusions and Outlook IN SILICO APPROACHES: DATA MANAGEMENT - BIOINFORMATICS Introduction Experimental Setup and Statistical Power Properties of Different Omics Data Statistical Methods Prediction and Classification Combining Different Omics Data and Biological Interpretations Data Management ROLE OF MODELING AND SIMULATION IN TOXICOLOGY PREDICTION Introduction The Need to Bring PK and PD in Predictive Models Together Methodological Aspects and Concepts Application During Lead Optimization Application During Clinical Candidate Selection Entry-into-Human Preparation and Translational PK/PD Modeling Justification of Starting Dose, Calculatin of Safety Margins, and Support of Phase I Clinical Trial Design Outlook and Conclusions GENOMIC APPLICATIONS FOR ASSESSING TOXICITIES OF LIVER AND KIDNEY INJURY Introduction Toxicogenomic Approaches Specific Applications of Toxicogenomics Toxicogenomic Applications for the Better Understanding of Hepatotoxicity Toxicogenomic Profiling of Nephrotoxicity Limitations of Toxicogenomics Conclusions USE OF TOXICOGENOMICS FOR MECHANISTIC CHARACTERIZATION OF HEPATOCARCINOGENS IN SHORTER TERM STUDIES Introduction Toxicogenomics Conclusions and Outlook DISCOVERY AND APPLICATION OF NOVEL BIOMARKERS Introduction Novel RNA Biomarkers DNA as a Biomarker Novel Biomarkers: Beyond Nucleotide-Based Discovery Summary and Outlook PREDICTIVE TOXICOLOGY: GENETICS, GENOMICS, EPIGENETICS, AND NEXT-GENERATION SEQUENCING IN TOXICOLOGY Introduction Technological Advances Applications in Toxicology Summary and Outlook BIOMARKERS AS TOOLS FOR PREDICTIVE SAFETY ASSESSMENT: NOVEL MARKERS OF DRUG-INDUCED KIDNEY INJURY Need and Search for Novel Biomarkers of Kidney Injury Urinary Biomarkers of Drug-Induced Kidney Injury Genomic Biomarkers Qualification and Use of Novel Kidney Injury Biomarkers in Preclinical Safety Assessment Summary and Perspectives THE USE OF RENAL CELL CULTURE FOR NEPHROTOXICITY INVESTIGATIONS Introduction In Vitro Renal Models Stem Cells Optimal Cell Culture Conditions In Vitro Nephrotoxicity Assessment Outlook THE ZEBRAFISH MODEL IN TOXICOLOGY The Need for a Physiologically Relevant Organ Model in Drug Toxicity Testing Extensive Knowledge about Genetics, Development, and Physiology of D. rerio Studies of Specific Organ Toxicities in Zebrafish Embryos and Larvae PREDICTIVE METHOD DEVELOPMENT: CHALLENGES FOR COSMETICS AND GENOTOXICITY AS A CASE STUDY Introduction The Toolbox of Predicitve Methods Genotoxicity as a Case Study The Way Forward: Combining In Silico and In Vitro Tools USING PLURIPOTENT STEM CELLS AND THEIR PROGENY AS AN IN VITRO MODEL TO ASSESS (DEVELOPMENTAL) NEUROTOXICITY Introduction Neurodevelopment In Vivo Main Principle of In Vitro Test Systems to Model DNT Requirements of an In Vitro Test System for DNT/NT Modeling of Disease and Toxicant-Induced Damage Using Stem Cells to Assess (Developmental) Neurotoxicity Limitations STEM CELL-BASED METHODS FOR IDENTIFYING DEVELOPMENTAL TOXICITY POTENTIAL Introduction Developmental Toxicity Screening: Past and Present Pluripotent Stem Cells Metabolomics Stem Cell-Based In Vitro Screens for Developmental Toxicity Testing Summary IMMUNOGENICITY OF PROTEIN THERAPEUTICS: RISK ASSESSMENT AND RISK MITIGATION Introduction The Central Role of CD4+ T Cells Generation of T-Cell Epitopes Tolerance to Therapeutic Drugs Tool Set for Immunogenicity Risk Assessment Immunogenicity Risk Mitigation The Integrated Strategy of Risk Minimization Summary REGULATORY ASPECTS The History of Medicines Regulations in Brief Impact on Drug Success of the Current ICH Nonclinical Testing Paradigm Actions Taken for Increasing the Drug Development Success Innovative Drugs: Impact on Nonclinical Development Strategies Envisaging a Paradigm Change Regulatory Actions Needed to Shift the Animal-Based Paradigm Index

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Details

  • NCID
    BB17405245
  • ISBN
    • 9783527336081
  • Country Code
    gw
  • Title Language Code
    eng
  • Text Language Code
    eng
  • Place of Publication
    Weinheim
  • Pages/Volumes
    xxv, 404 p.
  • Size
    25 cm
  • Classification
  • Subject Headings
  • Parent Bibliography ID
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