Divided into three major parts, the first section deals with novel technologies and includes the utility of adverse event reports to drug discovery, the translational aspects of preclinical safety findings, broader computational prediction of drug side-effects, and a description of the serotonergic system. The main part of the book looks at some of the most common antitarget-mediated side effects, focusing on hepatotoxicity in drug safety, cardiovascular toxicity and signaling effects via kinase and GPCR anti-targets. In the final section, several case studies of recently developed drugs illustrate how to prevent anti-target effects and how big pharma deals with them if they occur. The more recent field of systems pharmacology has gained prominence and this is reflected in chapters dedicated to the utility in deciphering and modeling anti-targets. The final chapter is concerned with those compounds that inadvertently elicit CNS mediated adverse events, including a pragmatic description of ways to mitigate these types of safety risks.
Written as a companion to the successful book on antitargets by Vaz and Klabunde, this new volume focuses on recent progress and new classes, methods and case studies that were not previously covered.
Laszlo Urban received his MD and PhD in neurophysiology/neuropharmacology in Hungary, and was visiting professor at Duke University between 1987 and 1989. He is currently global head of Preclinical Safety Profiling at the Novartis Institutes for Biomedical Research, Cambridge, USA, and was previously the Deputy Head of the Novartis Institute for Medical Sciences in London, UK. Dr. Urban has over 130 scientific articles, book chapters and patents to his name.
Roy J. Vaz received his PhD in organic chemistry from the University of Florida, Gainesville, an MBA from the University of Illinois, and most recently an MS in molecular biology from Lehigh University, USA. He is currently a senior distinguished scientist at Sanofi Pharmaceuticals in Waltham, MA, and was previously Director of the Investigative Product Optimization department under Aventis. He has worked at Bristol-Myers Squibb as Principal Scientist as well as at Tripos, Inc, as a research scientist. Dr. Vaz has authored or co-authored around 45 publications in peer-reviewed journals, eight book chapters and several patents.
Vinod Patel gained his BSc in applied chemistry from Leicester Polytechnic, and a PhD in synthetic organic chemistry from Nottingham University, UK. He took up a post-doctoral fellowship at the University of Rochester, NY, USA, before joining Eli Lilly & Company, where he spent the next nine years as a medicinal chemist in the oncology division. He then joined Kinetix Pharmaceuticals, which was acquired by Amgen and Dr. Patel joined their new Cambridge facility as head of medicinal chemistry. In 2011, he joined Sanofi oncology research as head of medicinal chemistry where he is currently head of chemical research in lead generation candidate realization. Dr. Patel has over 50 publications and some 50 patents to his name.
Laszlo Urban received his MD and PhD in neurophysiology/neuropharmacology in Hungary, and was visiting professor at Duke University between 1987 and 1989. He is currently global head of Preclinical Safety Profiling at the Novartis Institutes for Biomedical Research, Cambridge, USA, and was previously the Deputy Head of the Novartis Institute for Medical Sciences in London, UK. Dr. Urban has over 130 scientific articles, book chapters and patents to his name. Roy J. Vaz received his PhD in organic chemistry from the University of Florida, Gainesville, an MBA from the University of Illinois, and most recently an MS in molecular biology from Lehigh University, USA. He is currently a senior distinguished scientist at Sanofi Pharmaceuticals in Waltham, MA, and was previously Director of the Investigative Product Optimization department under Aventis. He has worked at Bristol-Myers Squibb as Principal Scientist as well as at Tripos, Inc, as a research scientist. Dr. Vaz has authored or co-authored around 45 publications in peer-reviewed journals, eight book chapters and several patents. Vinod Patel gained his BSc in applied chemistry from Leicester Polytechnic, and a PhD in synthetic organic chemistry from Nottingham University, UK. He took up a post-doctoral fellowship at the University of Rochester, NY, USA, before joining Eli Lilly & Company, where he spent the next nine years as a medicinal chemist in the oncology division. He then joined Kinetix Pharmaceuticals, which was acquired by Amgen and Dr. Patel joined their new Cambridge facility as head of medicinal chemistry. In 2011, he joined Sanofi oncology research as head of medicinal chemistry where he is currently head of chemical research in lead generation candidate realization. Dr. Patel has over 50 publications and some 50 patents to his name.
#01 Analysis of marketed drugs: The utility of AERS for early drug discovery/pitfalls
#02 In silico prediction of drug side effects
#03 Translational value of preclinical safety assessment: System organ class (SOC) representation of off-targets
#04 Pathological conditions associated with the disturbance of 5HT receptors
#05 Drug-induced Liver Injury ? Clinical and Diagnostic Aspects
#06 Mechanistic Safety Biomarkers for Drug-Induced Liver Injury
#07 In vitro models for the Prediction of Drug-Induced Liver Injury in Lead Discovery
#08 Transporters in the liver
#09 Mechanistic Modeling of Drug-Induced Liver Injury (DILI)
#10 Functional Cardiac Safety Evaluation of Novel Therapeutics
#11 Cav1.2
#12 Cardiac Sodium Current (Nav1.5)
#13 Circulating biomarkers for cardiotoxicity: reverse translation from human to preclinical species
#14 The Mechanistic Basis of hERG Blockade and the Proarrhythmic Effects Thereof
#15 Introduction to Kinase Anti-Targets
#16 Clinical and Nonclinical Adverse Effects of Kinase Inhibitors
#17 Cardiotoxicity of Kinase inhibitors
#18 Case Studies: Selective Inhibitors of Protein Kinases; Exploiting Demure Features
#19 Torcetrapib and Dalcetrapib Safety: Relevance of Preclinical In-Vitro and In-Vivo Models
#20 Targets associated with drug-related suicidal ideation and behavior
List of Contributors
Daniel J. Antoine
University of Liverpool
Institute of Translational Medicine
Department of Molecular and Clinical Pharmacology
MRC Centre for Drug Safety Science
Liverpool L69 3GE
UK
Richard J. Brennan
Sanofi US
Preclinical Safety
DSAR
153 2nd Ave.
Waltham, MA 02451
USA
Kim L.R. Brouwer
The University of North Carolina at Chapel Hill
UNC Eshelman School of Pharmacy
Division of Pharmacotherapy and Experimental Therapeutics
Chapel Hill, NC 27599
USA
José S. Duca
Novartis Institutes for BioMedical Research
Computer Assisted Drug Discovery
100 Technology Square
Cambridge, MA 02139
USA
Berengere Dumotier
Novartis Institutes for BioMedical Research
Preclinical Safety/Cardiac Electrophysiology
Klybeckstrasse 141, WKL.136.178
4057 Basel
Switzerland
Gül Erdemli
Novartis Institutes for BioMedical Research
Center for Proteomic Chemistry
Ion Channel Group
250 Massachusetts Ave.
Cambridge, MA 02139
USA
Ramy Farid
Schrödinger, Inc.
120 West Forty-Fifth Street, 17th Floor
New York, NY 10036
USA
Alexander Fekete
Novartis Institutes for BioMedical Research
Preclinical Safety
Preclinical Secondary Pharmacology
250 Massachusetts Avenue
Cambridge, MA 02139
USA
Oliver Flint
Bristol-Myers Squibb
Pharmaceutical Candidate
Optimization
Discovery Toxicology
Liberty Drive
Newtown, PA 18940
USA
Gary Gintant
AbbVie
Integrated Science and Technology
Department of Integrative Pharmacology
Abbott Park Road
Abbott Park, IL 60064
USA
Andrea Greiter-Wilke
F. Hoffmann-La Roche Ltd.
Pharmaceuticals/Metabolic DTA
Grenzacherstrasse 124
4070 Basel
Switzerland
Brian Guth
Boehringer Ingelheim Pharma GmbH & Co. KG
General Pharmacology, Drug Discovery Support
Biberach an der Riss
Germany
Robert L. Hamlin
QTest Labs LLC and The Ohio State University
1900 Coffey Road
Columbus, OH 43210
USA
Jacques Hamon
Novartis Institutes for BioMedical Research
Preclinical Safety Profiling
Klybeckstrasse 141
4057 Basel
Switzerland
Andreas Hartmann
Novartis Institutes for BioMedical Research
Preclinical Safety
Klybeckstrasse
4057 Basel
Switzerland
Brett A. Howell
The Hamner Institutes for Health Sciences
The Hamner–UNC Institute for Drug Safety Sciences
Research Triangle Park, NC 27709
USA
Daniel Hoyer
The University of Melbourne
Faculty of Medicine, Dentistry and Health Sciences
School of Medicine
Department of Pharmacology and Therapeutics
Parkville, Victoria 3010
Australia
and
The University of Melbourne
The Florey Institute of Neuroscience and Mental Health
30 Royal Parade
Parkville, Victoria 3052
Australia
and
The Scripps Research Institute
Department of Chemical Physiology
10550 North Torrey Pines Road
La Jolla, CA 92037
USA
Qi-Ying Hu
Novartis Institutes for BioMedical Research
Global Discovery Chemistry
100 Technology Square
Cambridge, MA 02139
USA
Haisong Ju
Novartis Institutes for BioMedical Research Head
Safety Pharmacology-US/Preclinical Safety
Novartis Pharmaceuticals Corporation
One Health Plaza
East Hanover, NJ 07936-1080
USA
Michael J. Keiser
University of California, San Francisco
Department of Pharmaceutical Chemistry
1700 4th Street
San Francisco, CA 94158
USA
and
University of California, San Francisco
Department of Bioengineering and
Therapeutic Sciences
1700 4th Street
San Francisco, CA 94158
USA
and
University of California, San Francisco
Institute for Neurodegenerative Diseases
675 Nelson Rising Lane
San Francisco, CA 94158
USA
Douglas A. Keller
Sanofi US
Preclinical Safety
DSAR
55 Corporate Dr.
Bridgewater, NJ 08807
USA
Gerd A. Kullak-Ublick
University Hospital Zurich
Department of Clinical Pharmacology and Toxicology
Raemistrasse 100
8091 Zurich
Switzerland
Pierre Lainée
Sanofi
DSAR 371, RUE DU PROF JOSEPH BLAYAC
Montpellier 34184
France
Ellen R. Laird
Array BioPharma Inc.
Computational Chemistry
3200 Walnut Street
Boulder, CO 80301
USA
Karen L. Leach
Pfizer
Centers for Therapeutic Innovation
3 Blackfan Circle
Boston, MA 02115
USA
Eugen Lounkine
Novartis Institutes for BioMedical Research
Center for Proteomic Chemistry
In Silico Lead Discovery
250 Massachusetts Avenue
Cambridge, MA 02139
USA
K. Andrew MacCannell
Novartis Institutes for BioMedical Research
100 Technology Square
Cambridge, MA 02139
USA
Mateusz Maciejewski
Novartis Institutes for BioMedical Research
Center for Proteomic Chemistry
Preclinical Safety Profiling
250 Massachusetts Avenue
Cambridge, MA 02139
USA
Frederic Moulin
Bristol-Myers Squibb
Pharmaceutical Candidate Optimization
Discovery Toxicology
Clover Lane
Madison, CT 06443
USA
Lutz Müller
F. Hoffmann-La Roche Ltd.
Pharmaceuticals/Metabolic DTA
Grenzacherstrasse 124
4070 Basel
Switzerland
Patrick Y. Müller
Novartis Pharma
Global Pharma Development Strategy
Fabrikstrasse
4057 Basel
Switzerland
Mark C. Munson
Sanofi US
LGCR-Boston Hub
153 2nd Ave
Waltham, MA, 02451
USA
Eric J. Niesor
F. Hoffmann-La Roche Ltd.
Pharmaceuticals/Metabolic DTA
Grenzacherstrasse 124
4070 Basel
Switzerland
Vinod F. Patel
Sanofi US
LGCR – Boston Hub
153 Second Avenue
Waltham, MA 02451
USA
Robert A. Pearlstein
Novartis Institutes for BioMedical Research
Computer Assisted Drug Discovery
100 Technology Square
Cambridge, MA 02139
USA
Sarita Pereira1)
Novartis Institutes for BioMedical Research
250 Massachusetts Avenue
Cambridge, MA 02139
USA
Dusty Sarazan
Data Sciences International
119 14th Street NW, Suite 100
St. Paul, MN 55112
USA
John R. Senior
Food and Drug Administration
Center for Drug Evaluation and Research
Office of Surveillance and Epidemiology
Office of Pharmacovigilance and Epidemiology
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
USA
Lisl K. Shoda
The Hamner Institutes for Health Sciences
The Hamner–UNC Institute for Drug Safety Sciences
Research Triangle Park, NC 27709
USA
Scott Q. Siler
The Hamner Institutes for Health Sciences
The Hamner–UNC Institute for Drug Safety Sciences
Research Triangle Park, NC 27709
USA
Matt Skinner
AstraZeneca R&D
Drug Safety and Metabolism
Alderley Park
Macclesfield SK10 4TG
UK
Bruno Stieger
University Hospital Zurich
Department of Clinical Pharmacology and Toxicology
Raemistrasse 100
8091 Zurich
Switzerland
Martin Traebert
Novartis Institutes for BioMedical Research
Preclinical Safety/Cardiac Electrophysiology
Klybeckstrasse 141, WKL.136.178
4057 Basel
Switzerland
Christian Trendelenburg
Novartis Institutes for BioMedical Research
Preclinical Safety
Klybeckstrasse 141,
4057 Basel
Switzerland
László Urbán
Novartis Institutes for BioMedical Research
Preclinical Safety
Preclinical Secondary Pharmacology
250 Massachusetts Avenue
Cambridge, MA 02139
USA
Jean-Pierre Valentin
UCB Biopharma
Investigative Toxicology, Non-Clinical Development
1420 Braine-l'Alleud
Belgium
Roy J. Vaz
Sanofi US
LGCR – Boston Hub
153 Second Avenue
Waltham, MA 02451
USA
Paul B. Watkins
The Hamner Institutes for Health Sciences
The Hamner–UNC Institute for Drug Safety Sciences
Research Triangle Park, NC...
| Erscheint lt. Verlag | 23.2.2015 |
|---|---|
| Reihe/Serie | Methods & Principles in Medicinal Chemistry |
| Methods and Principles in Medicinal Chemistry | Methods and Principles in Medicinal Chemistry |
| Sprache | englisch |
| Themenwelt | Naturwissenschaften ► Chemie |
| Technik | |
| Schlagworte | Antitarget • Arzneimittelsicherheit • Biomolekül • Biomolekül • Chemie • Chemistry • Clinical Pharmacology & Therapeutics • drug developement side effects hepatic cardiovascular toxicity kinases GPCRs • Drug Discovery & Development • Klinische Pharmakologie u. Therapie • Medical Science • Medizin • Pharmakologie • Toxicology • Toxikologie • Wirkstoffforschung • Wirkstoffforschung u. -entwicklung |
| ISBN-10 | 3-527-67366-0 / 3527673660 |
| ISBN-13 | 978-3-527-67366-7 / 9783527673667 |
| Informationen gemäß Produktsicherheitsverordnung (GPSR) | |
| Haben Sie eine Frage zum Produkt? |
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