Drug Discovery Toxicology: From Target Assessment to Translational Biomarkers

Yvonne Will, J. Eric McDuffie, Andrew J. Olaharski, Brandon D. Jeffy

John Wiley & Sons, 18.04.2016 - 584 Seiten

As a guide for pharmaceutical professionals to the issues and practices of drug discovery toxicology, this book integrates and reviews the strategy and application of tools and methods at each step of the drug discovery process.

• Guides researchers as to what drug safety experiments are both practical and useful
• Covers a variety of key topics – safety lead optimization, in vitro-in vivo translation, organ toxicology, ADME, animal models, biomarkers, and –omics tools
• Describes what experiments are possible and useful and offers a view into the future, indicating key areas to watch for new predictive methods
• Features contributions from firsthand industry experience, giving readers insight into the strategy and execution of predictive toxicology practices

Voransicht des Buches »

Ausgewählte Seiten

Inhalt

References 8	8

SmallMolecule Safety Lead Optimization 15	15

References 23	23

Safety assessment Strategies and Predictive Safety	27

Discovery and Development Strategies for Small Interfering RNas	39

Physicochemistry and the OffTarget Effects of Drug Molecules	55

The Need for Human Exposure Projection in the Interpretation	67

References	77

STEM CELLS IN TOxICOLOGY	331

a	346

Stem CellDerived Renal Cells and Predictive Renal In Vitro Models	365

Predictive Cardiac Hypertrophy Biomarkers in Nonclinical	387

Vascular Injury Biomarkers	397

Novel Translational Biomarkers of Skeletal Muscle Injury	407

Translational Mechanistic Biomarkers and Models for Predicting	416

References	424

Liver	95

Cardiac	130

Predictive In Vitro Models for assessment of Nephrotoxicity	160

Bone Marrow	172

Dermal Toxicity	182

In Vitro Methods in Immunotoxicity assessment	193

References	199

Predicting Organ Toxicity In VivoCentral Nervous System	214

Biomarkers Cell Models and In Vitro assays for Gastrointestinal Toxicology	227

Preclinical Safety assessment of Drug CandidateInduced Pancreatic	242

to the Pancreas	253

animal Models of Disease for Future Toxicity Predictions	263

The Use of Genetically Modified animals in Discovery Toxicology	298

Mouse PopulationBased Toxicology for Personalized Medicine	314

assessing and Predicting DrugInduced Kidney Injury Functional	431

Canine Kidney Safety Protein Biomarkers	443

Traditional Kidney Safety Protein Biomarkers and NextGeneration	446

MicroRNas as Novel Glomerular Injury Biomarkers in Rats	452

In Vitro to In Vivo Relationships with Respect to Kidney Safety Biomarkers	458

Novel Renal Biomarkers Translation to Humans	466

Best Practices in Preclinical Biomarker Sample Collections	477

Best Practices in Evaluating Novel Biomarker Fit for Purpose	489

Best Practices in Translational Biomarker Data analysis	495

Regulatory	500

References	506

References	525

aBBREVIaTIONS	540

Urheberrecht

Andere Ausgaben - Alle anzeigen

Drug Discovery Toxicology: From Target Assessment to Translational Biomarkers
Yvonne Will,J. Eric McDuffie,Andrew J. Olaharski,Brandon D. Jeffy
Eingeschränkte Leseprobe - 2016

Drug Discovery Toxicology: From Target Assessment to Translational Biomarkers
Yvonne Will
Keine Leseprobe verfügbar - 2016

Häufige Begriffe und Wortgruppen

acid activity addition adverse analysis animal animal models application approach assays assessment associated biomarkers blood candidate cardiac cause cell culture changes chemical clinical compared compounds concentrations considered culture detection determine differentiation DILI disease dose drug drug development drug discovery drug‐induced early effects et al evaluation example exposure expression factors function gene genetic glucose heart human identify important increased induced inhibition injury kidney lead levels limited lines liver markers measured mechanisms methods mice models molecular molecules mouse multiple muscle novel observed organ patients pharmaceutical Pharmacol plasma potential preclinical prediction primary produce protein regulatory relevant renal Research response risk rodent safety samples screening selection sensitive silico similar specific stem cells structure studies target testing therapeutic tion tissue toxicity Toxicol toxicology Translational transporters understanding utility validation vitro vivo

Autoren-Profil (2016)

Yvonne Will, PhD, is a Senior Director and the Head of Science and Technology Strategy, Drug Safety Research and Development at Pfizer, Connecticut, USA. She co-edited the book Drug-Induced Mitochondrial Dysfunction, published by Wiley in 2008.

J. Eric McDuffie, PhD, is the Director of the Discovery / Investigative Toxicology and Laboratory Animal Medicine groups at Janssen Research & Development, California, USA.

Andrew J. Olaharski, PhD, is an Associate Director of Toxicology at Agios Pharmaceuticals, Massachusetts, USA.

Brandon D. Jeffy, PhD, is a Senior Principal Scientist in the Exploratory Toxicology division of Nonclinical Development at Celgene Pharmaceuticals, California, USA.

Bibliografische Informationen

Titel	Drug Discovery Toxicology: From Target Assessment to Translational Biomarkers
Herausgeber	Yvonne Will, J. Eric McDuffie, Andrew J. Olaharski, Brandon D. Jeffy
Ausgabe	illustriert
Verlag	John Wiley & Sons, 2016
ISBN	1119053331, 9781119053330
Länge	584 Seiten

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