Drug Discovery Toxicology

From Target Assessment to Translational Biomarkers
Herausgeber: Will, Yvonne; Jeffy, Brandon D; Olaharski, Andrew J; McDuffie, J Eric

• Gebundenes Buch

Produktbeschreibung

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

---

Hinweis: Dieser Artikel kann nur an eine deutsche Lieferadresse ausgeliefert werden.

Produktdetails

• Verlag: John Wiley & Sons / Wiley
• Seitenzahl: 584
• Erscheinungstermin: 18. April 2016
• Englisch
• Abmessung: 282mm x 221mm x 36mm
• Gewicht: 1601g
• ISBN-13: 9781119053330
• ISBN-10: 1119053331
• Artikelnr.: 43114552

Autorenporträt

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.

Inhaltsangabe

LIST OF CONTRIBUTORS xxi FOREWORD xxv PART I INTRODUCTION 1 1 Emerging
Technologies and their Role in Regulatory Review 3 Thomas J. Colatsky
References 8 PART II SAFETY LEAD OPTIMIZATION STRATEGIES 13 2
Small-Molecule Safety Lead Optimization 15 Donna M. Dambach References 23 3
Safety Assessment Strategies and Predictive Safety of Biopharmaceuticals
and Antibody Drug Conjugates 27 Michelle J. Horner, Mary Jane Hinrichs and
Nicholas Buss References 36 4 Discovery and Development Strategies for
Small Interfering Rnas 39 Scott A. Barros and Gregory Hinkle References 49
PART III BASIS FOR IN VITRO-IN VIVO PK TRANSLATION 53 5 Physicochemistry
and the Off-Target Effects of Drug Molecules 55 Dennis A. Smith References
65 6 The Need for Human Exposure Projection in the Interpretation of
Preclinical In Vitro and In Vivo ADME Tox Data 67 Patrick Poulin
Abbreviations 77 References 77 7 A DME Properties Leading to Toxicity 82
Katya Tsaioun References 90 PART IV Predicting Organ Toxicity 93 8 Liver 95
J. Gerry Kenna, Mikael Persson, Scott Q. Siler, Ke Yu, Chuchu Hu, Minjun
Chen, Joshua Xu, Weida Tong, Yvonne Will and Michael D. Aleo References 121
9 Cardiac 130 David J. Gallacher, Gary Gintant, Najah Abi-Gerges, Mark R.
Davies, Hua Rong Lu, Kimberley M. Hoagland, Georg Rast, Brian D. Guth, Hugo
M. Vargas and Robert L. Hamlin References 152 10 Predictive In Vitro Models
for Assessment of Nephrotoxicity and Drug-Drug Interactions In Vitro 160
Lawrence H. Lash References 170 11 Predicting Organ Toxicity In Vitro: Bone
Marrow 172 Ivan Rich and Andrew J. Olaharski References 180 12 Predicting
Organ Toxicity In Vitro: Dermal Toxicity 182 Patrick J. Hayden, Michael
Bachelor, Mitchell Klausner and Helena Kandárová References 189 13 In Vitro
Methods in Immunotoxicity Assessment 193 Xu Zhu and Ellen Evans References
199 14 Strategies and Assays for Minimizing Risk of Ocular Toxicity during
Early Development of Systemically Administered Drugs 201 Chris J. Somps,
Paul Butler, Jay H. Fortner, Keri E. Cannon and Wenhu Huang References 210
15 Predicting Organ Toxicity In Vivo--Central Nervous System 214 Greet
Teuns and Alison Easter Abbreviations 223 References 224 16 Biomarkers,
Cell Models, and In Vitro Assays for Gastrointestinal Toxicology 227
Allison Vitsky and Gina M. Yanochko References 236 17 Preclinical Safety
Assessment of Drug Candidate-Induced Pancreatic Toxicity: From an Applied
Perspective 242 Karrie A. Brenneman, Shashi K. Ramaiah and Lauren M.
Gauthier Acknowledgments 258 References 258 PART V A DDRESSING THE FALSE
NEGATIVE SPACE--INCREASING PREDICTIVITY 261 18 Animal Models of Disease for
Future Toxicity Predictions 263 Sherry J. Morgan and Chandikumar S.
Elangbam References 287 19 The Use of Genetically Modified Animals in
Discovery Toxicology 298 Dolores Diaz and Jonathan M. Maher References 309
20 Mouse Population-Based Toxicology for Personalized Medicine and Improved
Safety Prediction 314 Alison H. Harrill References 326 PART VI STEM CELLS
IN TOXICOLOGY 331 21 Application of Pluripotent Stem Cells in Drug-Induced
Liver Injury Safety Assessment 333 Christopher S. Pridgeon, Fang Zhang,
James A. Heslop, Charlotte M.L. Nugues, Neil R. Kitteringham, B. Kevin Park
and Christopher E.P. Goldring References 342 22 Human Pluripotent Stem
Cell-Derived Cardiomyocytes: A New Paradigm in Predictive Pharmacology and
Toxicology 346 Praveen Shukla, Priyanka Garg and Joseph C. Wu
Acknowledgments 360 References 360 23 Stem Cell-Derived Renal Cells and
Predictive Renal In Vitro Models 365 Jacqueline Kai Chin Chuah, Yue Ning
Lam, Peng Huang and Daniele Zink Acknowledgments 379 Notes 379 References
379 PART VII CURRENT STATUS OF PRECLINICAL IN VIVO TOXICITY BIOMARKERS 385
24 Predictive Cardiac Hypertrophy Biomarkers in Nonclinical Studies 387
Steven K. Engle References 393 25 Vascular Injury Biomarkers 397 Tanja S.
Zabka and Kaïdre Bendjama References 403 26 Novel Translational Biomarkers
of Skeletal Muscle Injury 407 Peter M. Burch and Warren E. Glaab References
412 27 Translational Mechanistic Biomarkers and Models for Predicting
Drug-Induced Liver Injury : Clinical to In Vitro Perspectives 416 Daniel J.
Antoine References 424 PART VIII Kidney Injury Biomarkers 429 28 Assessing
and Predicting Drug-Induced Kidney Injury, Functional Change, and Safety in
Preclinical Studies in Rats 431 Yafei Chen References 439 29 Canine Kidney
Safety Protein Biomarkers 443 Manisha Sonee References 445 30 Traditional
Kidney Safety Protein Biomarkers and Next-Generation Drug-Induced Kidney
Injury Biomarkers in Nonhuman Primates 446 Jean-Charles Gautier and
Xiaobing Zhou References 447 31 Rat Kidney MicroRNA Atlas 448 Aaron T.
Smith References 449 32 MicroRNAs as Next-Generation Kidney Tubular Injury
Biomarkers in Rats 450 Heidrun Ellinger-Ziegelbauer and Rounak Nassirpour
References 451 33 MicroRNAs as Novel Glomerular Injury Biomarkers in Rats
452 Rachel Church References 453 34 Integrating Novel Imaging Technologies
to Investigate Drug-Induced Kidney Toxicity 454 Bettina Wilm and Neal C.
Burton References 456 35 In Vitro to In Vivo Relationships with Respect to
Kidney Safety Biomarkers 458 Paul Jennings References 460 36 Case Study:
Fully Automated Image Analysis of Podocyte Injury Biomarker Expression in
Rats 462 Jing Ying Ma References 465 37 Case Study: Novel Renal Biomarkers
Translation to Humans 466 Deborah A. Burt References 467 38 Case Study:
Microrn as as Novel Kidney Injury Biomarkers in Canines 468 Craig Fisher,
Erik Koenig and Patrick Kirby References 470 39 Novel Testicular Injury
Biomarkers 471 Hank Lin References 473 PART IX Best Practices in Biomarker
Evaluations 475 40 Best Practices in Preclinical Biomarker Sample
Collections 477 Jaqueline Tarrant References 480 41 Best Practices in Novel
Biomarker Assay Fit-for-Purpose Testing 481 Karen M. Lynch References 487
42 Best Practices in Evaluating Novel Biomarker Fit for Purpose and
Translatability 489 Amanda F. Baker References 493 43 Best Practices in
Translational Biomarker Data Analysis 495 Robin Mogg and Daniel Holder
References 498 44 Translatable Biomarkers in Drug Development: Regulatory
Acceptance and Qualification 500 John-Michael Sauer, Elizabeth G. Walker
and Amy C. Porter References 506 PART X Conclusions 509 45 Toxicogenomics
in Drug Discovery Toxicology: History, Methods, Case Studies, and Future
Directions 511 Brandon D. Jeffy, Joseph Milano and Richard J. Brennan
References 525 46 Issue Investigation and Practices in Discovery Toxicology
530 Dolores Diaz, Dylan P. Hartley and Raymond Kemper References 538
ABBREVIATIONS 540 CONCLUDING REMARKS 542 INDEX 543