
Translation of Preclinical Drug–Drug Interaction and Metabolism Data into Risk Assessment of Clinical Toxicity
Monday, October 21, 2013
Presented By
Drug discovery and development of new chemical entities now includes more assays to better predict human ADME-TOX (absorption-distribution-metabolism-excretion-toxicity) and DDI (drug–drug interaction) profiles. Despite the progress to date, however, the translation of ADME-TOX-DDI data remains challenging. In many cases, human ADME-TOX-DDI profiles are not well modeled in the absence of clinical data. This symposium covers new in vivo, in vitro and in silico approaches to study ADME-TOX-DDI and explores data integration to better evaluate human risk.
*Networking reception to follow.
Registration and Webinar Pricing
Member | $30 |
Student/Postdoc Member | $15 |
Nonmember (Academia) | $65 |
Nonmember (Corporate) | $85 |
Nonmember (Non-profit) | $65 |
Nonmember (Student / Postdoc / Resident / Fellow) | $45 |
The Predictive Toxicology Discussion Group is proudly supported by:
Mission Partner support for the Frontiers of Science program provided by 
Agenda
* Presentation titles and times are subject to change.
Monday October 21, 2013 | |
8:30 AM | Registration and Continental Breakfast |
9:00 AM | Welcome and Introduction |
Session I: Clinical Pharmacology Considerations | |
9:15 AM | Exploring the Clinical Importance of Drug-Drug Interactions |
9:55 AM | Challenges in CYP2D6 Phenotype Assignment from Genotype Data for Clinical Implementation: A Critical Assessment and Call for Standardization |
10:35 AM | Coffee break |
Session II: Drug–drug-Interactions, Toxicity and Transporters: Lessons Learned in Industry | |
11:00 AM | Transporters and their Role in PK-ADME-TOX: Implications for Drug Discovery and Development |
11:40 AM | Managing Functional Consequences of Variability in Drug Bioavailability, Exposure and Pharmacological Responses |
12:20 PM | Networking lunch break |
Session III: UGTs | |
1:20 PM | Potential Effects on Drug–Drug Interactions and Disease Susceptibility by Regulation of UGT Activity/Expression via Epigenetic Mechanisms (miRNA) and Alternate Splicing |
2:00 PM | Endoplasmic reticulum-bound UDP-UGTs and their Interactions with Kinases to Dictate Substrate Selections |
2:40 PM | Coffee break |
Session IV: Reactive Metabolites and Preclinical Models of Idiosyncratic Toxicity | |
3:10 PM | Metabolic activation and reactive metabolites |
3:50 PM | Drug-cytokine interactions: Predictors of IDILI |
4:30 PM | Animals models for idiosyncratic toxicity |
5:10 PM | Networking reception |
6:00 PM | Close |
Speakers
Organizers
Myrtle Davis, DVM, PhD
The National Cancer Institute, NIH
Dr. Myrtle Davis earned a PhD in Toxicology from the University of Illinois Champaign-Urbana in and completed a post-doctoral fellowship in Toxicologic Pathology at the University of Maryland. She completed Undergraduate work in Chemistry and obtained her Doctor of Veterinary Medicine degree from Tuskegee University School of Veterinary Medicine. Dr. Davis. is the currently the Branch Chief for Toxicology and Pharmacology in the Developmental Therapeutics Program of the Division of Cancer Diagnostics and Treatment of the NCI. Dr. Davis moved to NIH and the National Cancer Institute from Lilly Research Labs, Eli Lilly and company where she held the position of Research Advisor in the Investigative Toxicology Group. Prior to taking the position at Eli Lilly, Dr. Davis was an Associate Professor in the Department of Pathology at the University of Maryland, School of Medicine where she had an active research program exploring mechanisms of toxicant-induced apoptosis and the role of protein phosphorylation.
Raymond A. Kemper, PhD, DABT
Merck
Dr. Ray Kemper received his bachelor's degree in Chemistry and his PhD in Toxicology from the University of Louisville. He then went on to do postdoctoral training in the Dept. of Comparative Biosciences at the University of Wisconsin in Madison. In 1999, Ray joined the Biochemical Toxicology group at DuPont Haskell Laboratory in Newark DE, where his work focused on comparative ADME and investigative toxicology. In 2003 joined the Discovery Toxicology group at DuPont and became involved in development of predictive models to support early ADME and toxicity screening. In 2005, Ray moved to Boehringer Ingelheim Pharmaceuticals in Ridgefield CT and established an Exploratory Toxicology group within Nonclinical Drug Safety to provide on early toxicology support for small molecule discovery programs. In 2011, Ray joined the Early and Investigative Safety section at Hoffman La Roche in Nutley, NJ as head of Mechanistic Safety-US. In January 2013, Ray moved to Merck Research Labs in Boston, joining the Discovery Sciences Support section of the Safety Assessment department. Ray is a Diplomate of the American Board of Toxicology and an active member of SOT, ISSX and ACS.
Marla Weetall, PhD
PTC Therapeutics
Marla Weetall, PhD has worked at PTC Therapeutics since 2002 in Drug Discovery and Development. Prior to joining PTC, she worked at Novartis/ Sandoz Pharmaceuticals. Her efforts have supported the identification and selection of 8 compounds for development, of which 4 have moved into the clinic. Dr. Weetall and has co-organized 12 NY Acad. Science meetings for the Biochemical Pharmacology Discussion and the Predictive Toxicology Groups. Dr. Weetall received a B.S. in Biochemistry from Cornell University and a PhD in Biophysical Chemistry from Cornell University.
Jennifer S. Henry, PhD
The New York Academy of Sciences
Speakers
Andrea Gaedigk, PhD
Children's Mercy Hospital
Dr Gaedigk received her MSc and PhD degrees in Biology from the University of Stuttgart, Germany. Upon completion of her doctoral studies at the Margarete-Fischer-Bosch-Institute of Clinical Pharmacology (Stuttgart, Germany) and the Biocenter, University of Basel, Switzerland, she trained as a postdoctoral fellow at the Hospital for Sick Children in the Department of Clinical Pharmacology in Toronto, Canada and held a position as Research Associate thereafter (1994-1996). In 1996, Dr. Gaedigk moved to Kansas City, MO, USA, where she accepted a position as Associate Director in the NICHD Pediatric Pharmacology Research Unit Lab at the Children's Mercy Hospital; she also joined the faculty as Assistant Professor at the University of Missouri Kansas City (UMKC) School of Medicine. Since 2000 Dr Gaedigk directs the Pharmacogenetics Core Laboratory in the Division of Clinical Pharmacology and Therapeutic Innovation. She was promoted to Associate Professor in 2005 and to Professor in September of this year. She also holds an adjunct faculty position at the Department of Clinical Laboratory Sciences, University of Kansas Medical Center.
Dr Gaedigk has published over 100 peer-reviewed articles in national and international journals, presented over 135 abstracts, reviewed for 49 journals and is a member of the editorial boards of Pharmacogenomics and the European Journal of Clinical Pharmacology. She is also actively involved in the American Society of Clinical Pharmacology (ASCPT) where she currently serves on the Board of Directors and chairs the Coordinating Committee for Scientific Sections. She is also an active member of the American Society for Experimental Pharmacology and Therapeutics (ASPET) and the International Society for the Study of Xenobiotics (ISSX).
Dr Gaedigk has a long-standing interest in genes involved in the metabolism and disposition of clinically used drug. She has extensively worked with cytochrome P450s and characterized their genetic variation in many diverse adult and pediatric populations in clinical and basic research settings. She is a leading expert in the pharmacogenetics of CYP2D6 and the implementation of genotype data into clinical practice. As a member of the Clinical Pharmacogenetics Implementation Consortium (CPIC) she is a key contributor to CYP2D6 gene/drug pair dosing guidelines.
Sean Hennessy, PharmD, PhD
University of Pennsylvania
Sean Hennessy is Associate Professor of Epidemiology and of Pharmacology and Director of the Center for Pharmacoepidemiology Research and Training at the Perelman School of Medicine at the University of Pennsylvania (Penn). His research focus is pharmacoepidemiologist, which is the use of population research methods to study the effects of medications. Within pharmacoepidemiology, he focuses on drug-drug interactions and comparative effectiveness research. He is a Past President of the International Society for Pharmacoepidemiology (ISPE) and a past chair of the Drug Safety Scientific Section of the American Society for Clinical Pharmacology and Therapeutics. He is Editor for the Americas of the journal Pharmacoepidemiology & Drug Safety, co-editor of the book Pharmacoepidemiology, 5th edition, and serves on the editorial board of the journal Clinical Pharmacology and Therapeutics. He is the Principal Investigator of a NIH-funded study examining the clinical importance of drug-drug interactions, and of a NIH-funded training grant in pharmacoepidemiology. He helps to lead the FDA-funded Mini-Sentinel Initiative. In addition to his research and teaching, he leads a clinical program to improve outpatient medication use within the University of Pennsylvania Health System and co-leads Penn's global health partnership with Cayetano Heredia University in Peru.
Philip Lazarus, PhD
Washington State University College of Pharmacy
Dr. Lazarus' research has focused on the general areas of metabolism, gene-environment interactions, and pharmacogenetics. Specifically, he has taken a targeted pathway approach to establishing how environmental or drug exposures interact with genetic variation in relevant pathways to alter disease risk or patient response to an agent/drug. This research has spanned the spectrum of cancer causation, prevention and treatment, focusing on: (i) tobacco carcinogen metabolism and cancer susceptibility; (ii) nicotine metabolism and pharmacogenetics, (iii) pharmacogenetics of chemotherapeutic agents, particularly focusing on agents used for the prevention and treatment of breast cancer, (iv) pharmacogenetics of 2nd-generation antipsychotics, and (v) the regulation of metabolism by epigenetic pathways and differential splicing. Dr. Lazarus has served as the Associate Director of the Division of Population Sciences and Program Leader of the Cancer Control and Molecular Epidemiology Program at the Penn State Cancer Institute (2003-2010), the Director for the Center for Pharmacogenetics at Penn State University (2009-2012) and now serves as Chair of the Department of Pharmaceutical Sciences at the College of Pharmacy, Washington State University.
R. Scott Obach, PhD
Pfizer
Scott Obach is a Senior Research Fellow in the Pharmacokinetics, Dynamics, and Drug Metabolism Department at Pfizer in Groton, CT. He earned his PhD in biochemistry from Brandeis University in 1990, followed by a post-doctoral fellowship in 1990-1992 at the New York State Department of Health Research Laboratories. In 1992, Scott joined the Drug Metabolism Department at Pfizer Inc. as a Research Scientist. He currently serves on the editorial boards of Drug Metabolism and Disposition, Chemical Research in Toxicology, Drug Metabolism and Pharmacokinetics, and Xenobiotica. He is an author or coauthor on over 150 research publications and has given invited oral presentations at over sixty scientific conferences. His research interests include application of in vitro approaches to study drug metabolism, prediction of human pharmacokinetics and drug interactions, mechanisms of cytochrome P450 catalysis and other biotransformation reactions, including generation of chemically reactive metabolites.
Ida S. Owens, PhD
National Institute of Child and Human Development, NIH
Ida Stephens Owens received her PhD in Biochemistry and Physiology from Duke University. A native of Whiteville, NC, Dr. Owens graduated summa cum laude from North Carolina College, now North Carolina Central University. In 1975, as a member of the Laboratory of Developmental Pharmacology in the National Institute of Child Health and Human Development (NICHD) at the National Institutes of Health in Bethesda, MD, Dr. Owens initiated a research program investigating the UGT drug detoxifying system that is now recognized for its studies on the genetics of human diseases. In 1981, this research program was extended and made into a permanent Section on Drug Biotransformation, and Ida Stephens Owens was named Chief. She was first to determine genetic defects in children with Crigler-Najjar diseases, thereby uncovering for the first time the unique 13-gene UGT1A complex locus, which was been subsequently studied for its relationship to population genetics and other UGT-based biochemical reactions. Currently serving as the Head of the Section on Genetic Disorders of Drug Metabolism in the Program on Developmental Endocrinology and Genetics (NICHD), Dr. Owens has shown that each of 6/19 UGT isozymes that she has studied has the unique capacity to detoxify innumerable chemicals derived from metabolism, diet, environmental contaminants and medications. Her recent publications indicate whereas each isozyme has a non-fixed element (active-site) that is altered by classic, but isozyme-specific, phosphate signaling enables instant change and unlimited chemical detoxification. Having received the NIH-Director's award in 1992, Dr. Owens is recognized throughout the world for her work on drug detoxifying enzymes. She has written key publications in scientific journals on the genetics of this enzyme system and has been invited to speak at many national and international scientific conferences in this field. Dr. Owens is also a member of several leading scientific societies. She was recently awarded the inaugural Distinguished Alumni Award from Duke University, where her portrait hangs in a prominent parlor on that campus.
A. David Rodrigues, PhD
Bristol-Myers Squibb
David has been in the pharmaceutical industry for 23 years and currently is an employee of Bristol-Myers Squibb (BMS), serving as a Senior Research Fellow in the Pharmaceutical Candidate Optimization (PCO) organization (Lawrenceville, NJ). He served as Executive Director (Metabolism & PK) for ~10 years prior to joining the Research track. Before joining BMS in 2003, he worked at Merck, G. D. Searle and Abbott. Prior to joining the pharmaceutical industry in 1990, David studied in England and graduated with a B.Sc degree and a PhD Upon graduation, he joined the laboratory of Dr. Russell Prough and conducted postdoctoral studies (University of Louisville School of Medicine, Louisville, KY). David is interested in the application of in vitro drug metabolism techniques, animal models, integrative and translational PK-ADME science, problem solving, and the discovery and development of new chemical entities. He has (co-)authored over one hundred peer-reviewed manuscripts, and numerous book chapters, and has presented at over 40 symposia/meetings. He is an AAPS Fellow and has served on the ISSX Scientific Affairs Committee. David has served on the Editorial Board of numerous drug metabolism journals and currently serves as Associate Editor of Xenobiotica. He has also served as Editor/co-Editor of 4 books (3 related to drug interactions and one related to drug metabolism).
Robert A. Roth, PhD, DABT
Michigan State University
Dr. Robert Roth received his bachelor's degree in chemistry from Duke University and the PhD degree in biochemical toxicology from The Johns Hopkins University. After postdoctoral training at Yale University, he joined the faculty at Michigan State University in 1977, where he is currently Professor of Pharmacology and Toxicology. He is active in the Center for Integrative Toxicology at MSU, for which he serves as Director of the multidisciplinary graduate program in Environmental and Integrative Toxicological Sciences. In the Society of Toxicology (SOT), Dr. Roth has served as Chair of the Board of Publications and of the Awards Committee and as a member of several other committees, including the SOT Council. He has also been President of the Mechanisms and Food Safety Specialty Sections and has been Associate Editor of Toxicology and Applied Pharmacology and the Journal of Pharmacology and Experimental Therapeutics. He is a Diplomate of the American Board of Toxicology and has served on its Board of Directors. Dr. Roth has received several awards, including the Burroughs-Wellcome Toxicology Scholar Award, a Merit Award from the NIH, the Astra-Zeneca Traveling Lectureship Award from the SOT and a Distinguished Faculty Award from MSU. He has published over 250 peer-reviewed research articles and reviews in the areas of pulmonary and hepatic toxicology. His current research interests focus on (1) the role of the hemostatic system in the progression of acetaminophen hepatotoxicity and (2) inflammatory stress as a determinant of susceptibility to drug-induced liver injury. In the latter context, he and his colleagues have been working to develop animal and cell-based models for idiosyncratic drug-induced liver injury, with the ultimate goal of understanding mechanisms and developing assays that can predict more effectively which drug candidates are likely to cause these adverse reactions.
Jack Uetrecht, MD, PhD
University of Toronto
Dr. Uetrecht is Professor of Pharmacy and Medicine and the Canada Research Chair in Adverse Drug Reactions. He received his PhD in organic chemistry at Cornell University, MD at Ohio State University and did his internal medical residency at the University of Kansas Medical Center. He completed his clinical pharmacology fellowship in 1981 at Vanderbilt University and then joined the faculty as an assistant professor. He moved to the University of Toronto in 1985 and was the associate dean of pharmacy from 1994 to 1998. He was awarded the Canada Research Chair in Adverse Drug Reactions in 2001 and is a Fellow of the Canadian Academy of Health Sciences. His research is focused on the mechanism of idiosyncratic drug reactions. He is on the editorial board of Chemical Research in Toxicology, Current Drug Metabolism, Drug Metabolism Reviews, Expert Opinion on Drug Metabolism and Toxicology, and Drug Metabolism Letters. He chaired the Medical Research Council of Canada grants committee for Pharmaceutical Sciences from 1992-1997 and chaired the Health Canada Scientific Advisory Panel for Hepatotoxicity. He has appeared before the FDA and the EMA on several occasions. He received the Janssen-Ortho Research award in 2001, the Student's Administrative Council Undergraduate Teaching Award in 2005, the McEwan Lectureship in 2007 and was voted Teacher of the Year by the 3rd year class in 2007, 2008, 2009, and 2012.
Joseph A. Ware, PhD
Genentech
Joseph Ware is a Senior Scientist in Clinical Pharmacology at Genentech, Inc. Since 2007, his primary responsibilities at Genentech include development of an integrated Clinical Pharmacology strategy to support oncology small molecule candidate drug development and global registration. In addition to his activities in gRED Clinical Pharmacology, Joseph is an original member of the International Transport Consortia (ITC) which includes many scientists from academia, FDA, and industry. Collectively, the ITC published Membrane Transporters in Drug Development in Nature Reviews Drug Discovery in 2010 to aid drug development in this rapidly evolving field. Most recently and in collaboration with the Benet Lab at UCSF, Joseph has been investigating the impact of pH-dependent solubility on the absorption of anti-cancer drugs.
Joseph obtained his BS in Pharmacy and PhD in Pharmaceutical Sciences from Wayne State University. He completed his post-doctoral training under the mentorship of Dr. Lance R. Pohl in the Molecular Toxicology Section, Laboratory of Molecular Immunology, NHLBI, NIH. While at the NHLBI, he also studied renal transporters with Dr. Mark Knepper in the LKEM. Following completion of his fellowship, Joseph joined the Pharmacia and Upjohn Company in Kalamazoo Michigan. While at Pharmacia he initiated a cross-functional transporter biology platform with connectivity to drug discovery, toxicology, and clinical pharmacology. In September of 2003, Joseph transferred to Pfizer Ann Arbor where he had the opportunity to incorporate genetically modified mice into the preclinical drug disposition setting. During his industrial tenure, Joseph has mentored numerous undergraduate, graduate and post-graduate training fellows and has served as an adjunct professor at the University of Kansas and the University of West Virginia. He is currently a lecturer and contributor to the NIH Principles of Clinical Pharmacology.
Sponsors
Promotional Partner
The New York Academy of Medicine
The Predictive Toxicology Discussion Group is proudly supported by:
Mission Partner support for the Frontiers of Science program provided by 
Abstracts
Exploring the Clinical Importance of Drug-Drug Interactions
Sean Hennessy, PharmD, PhD, University of Pennsylvania
The goals of DDI research include screening for previously unanticipated DDIs; elucidating their potential pharmacokinetic and/or pharmacodynamic mechanisms; predicting and examining their effects on pharmacokinetic and clinical outcomes; and developing and evaluating approaches to manage their risks in clinical settings. The approaches used to study DDIs include in-vitro, in-vivo, in-silico, and in-populo (pharmacoepidemiologic) studies. Pharmacoepidemiologic studies can provide compelling evidence about the clinical effects of DDIs and help to elucidate time-course, susceptible populations, and mechanisms. Closer collaboration between pharmacoepidemiologists and clinical and laboratory scientists studying DDIs is needed to predict, confirm, and elucidate DDIs and thus reduce their adverse clinical and public health impact.
Potential Effects on Drug–Drug Interactions and Disease Susceptibility by Regulation of UGT Activity/Expression via Epigenetic Mechanisms (miRNA) and Alternate Splicing
Philip Lazarus, PhD, Washington State University College of Pharmacy
In silico analysis identified microRNA 491-3p as a potential regulator of the UGT1A gene family. Transfection of miR-491-3p mimic into HuH-7 cells significantly repressed UGT1A1 (p<0.0001) and UGT1A6 mRNA levels (p=0.0367) and this correlated with a significant reduction in the metabolism of raloxifene into raloxifene-6-glucuronide (ral-6-gluc; p=0.0067) and raloxifene-4'-glucuronide (p=0.0044). When endogenous miR-491-3p expression levels in HuH-7 cells are repressed, there is a significant increase (~80%; p=0.002) in UGT1A1 mRNA and a corresponding increase in glucuronidation of raloxifene into raloxifene-6-glucuronide (50%, p=0.0292) and raloxifene-4'-glucuronide (22%, p=0.0048). Knockdown of miR-491-3p in HepG2 cells did not significantly alter UGT1A1 mRNA levels, but did increase the formation of raloxifene-6-glucuronide (50%, p=0.0361) and raloxifene-4'-glucuronide (34%, p=0.0002). These results suggest that UGT1A1 protein expression is regulated by miR-491-3p in liver cancer cell lines and may reflect endogenous UGT1A1 regulation in human tissues expressing both UGT1A1 and miR-491-3p.
While differential splicing has been previously reported for several UGT genes including the UGT1A loci and UGT2B4, the levels of these splice variants tend to be low relative to the wild-type isozyme. We have identified a novel exon 3 deletion splice variant for UGT2A1 (termed 'UGT2A1Δexon3'). As determined by reverse-transcription and real-time PCR, UGT2A1Δexon3 was shown to be expressed in various tissues, comprising 10-45% of total enzyme expression in lung, trachea, larynx, tonsil, and colon. Using an inducible cell culture model, this splice variant effectively decreased wild-type UGT2A1 isozyme activity in a 1:1 stoichiometry. Co-immunoprecipitation experiments suggested the formation of wild-type UGT2A1_i1 and variant UGT2A1_i2 hetero-oligomers, as well as an UGT2A1_i1 homo-oligomer, indicating oligomerization of the UGT2A1 enzyme as a potential mechanism of alteration of function by the UGT2A1 splice variant.
These studies suggest that epigenetic and splicing pathways are important in the regulation of UGT metabolizing enzyme genes. Studies are underway to determine how these modes of regulation differ between individuals and to determine their potential effect on an individual's response to different agents.
Transporters and their Role in PK-ADME-TOX: Implications for Drug Discovery and Development
David Rodrigues, PhD, Bristol-Myers Squibb
Managing Functional Consequences of Variability in Drug Bioavailability, Exposure and Pharmacological Response
Joseph A. Ware, PhD, Genentech
Drug-Cytokine Interactions: Predictors of Idiosyncratic, Drug-Induced Liver Injury?
Robert A. Roth, PhD, DABT, Michigan State University
IDILI reactions are poorly understood, but several hypotheses to explain IDILI etiology exist and are consistent with roles for these cytokines in the hepatopathogenesis. According to the adaptive immunity hypothesis, a drug or its metabolite prompts a damaging adaptive immune response, but factors involved in hepatocellular killing are unknown. In a rodent model of autoimmune liver injury caused by concanavalin A (con A), CD4+ T cells and eosinophils as well as IFNg and TNF were critical mediators of injury. Observations that some xenobiotic agents can potentiate con A-induced injury raise the possibility that drugs might synergize with these cytokines in producing liver damage. The multiple determinant hypothesis of IDILI proposes that the intersection of several susceptibility factors during drug exposure results in liver injury. In an animal model of halothane hepatitis based on this hypothesis, a confluence of human susceptibility factors resulted in liver injury in mice; the liver injury was associated with TNF and IFNg production, and mice deficient in IFNg were insensitive to injury. The inflammatory stress hypothesis suggests that an acute inflammatory episode occurring during drug therapy precipitates an hepatotoxic response to an otherwise innocuous drug. Rodent models have been developed for several IDILI-associated drugs in which a harmless inflammatory episode elicited by lipopolysaccharide (LPS) synergizes with an innocuous drug exposure to yield pronounced liver injury. In one of these models developed with trovafloxacin (TVX), enhanced appearance of both IFNg and TNF occurred, and the liver injury depended on both of these cytokines.
These observations in animal models suggest roles for TNF and IFNg in IDILI pathogenesis. Interestingly, the sensitivity of cultured hepatocytes to killing by these cytokines is enhanced by TVX and other drugs that cause IDILI in human patients. Together, these results suggest that TNF and IFNg are likely to be produced during idiosyncratic reactions and can act synergistically with drugs to kill hepatocytes. Such drug-cytokine interaction might form the basis for cell-based assays designed to predict the IDILI potential of drug candidates.
Challenges in CYP2D6 Phenotype Assignment from Genotype Data for Clinical Implementation: A Critical Assessment and Call for Standardization
Andrea Gaedigk, PhD, Children's Mercy Hospital
This presentation will provide a summary of the complexity of the CYP2D6 gene locus and ensuing challenges for genotype analysis and highlight the major challenges for phenotype classification. Furthermore the advantages of a universal system that categorizes genotypes into a continuum of activity scores rather than using the traditional poor, intermediate, extensive and ultrarapid metabolizer labels, and their direct translation into clinically actionable recommendations will be presented.
Metabolic Activation and Reactive Metabolites
R. Scott Obach, PhD, Pfizer
Animal Models for Idiosyncratic Toxicity
Jack Uetrecht, MD, PhD, University of Toronto
Endoplasmic reticulum-bound UDP-Glucuronosyltransferases Interact with Kinases in order to Dictate Substrate Selections
Ida S. Owens, PhD, National Institute of Child and Human Development, NIH
Travel & Lodging
Our Location
The New York Academy of Sciences
7 World Trade Center
250 Greenwich Street, 40th floor
New York, NY 10007-2157
212.298.8600
Hotels Near 7 World Trade Center
Recommended partner hotel
Club Quarters, World Trade Center
140 Washington Street
New York, NY 10006
Phone: 212.577.1133
The New York Academy of Sciences is a member of the Club Quarters network, which offers significant savings on hotel reservations to member organizations. Located opposite Memorial Plaza on the south side of the World Trade Center, Club Quarters, World Trade Center is just a short walk to the Academy.
Use Club Quarters Reservation Password NYAS to reserve your discounted accommodations online.
Other nearby hotels
212.945.0100 | |
212.693.2001 | |
212.385.4900 | |
212.269.6400 | |
212.742.0003 | |
212.232.7700 | |
212.747.1500 | |
212.344.0800 |