Volume 35
Issue 1, 2015
ISSX President’s Message By John O. Miners, ISSX President Firstly, I would like to extend my best wishes to all members of ISSX for the New Year—2015 promises to be another busy and productive year for the Society. As I indicated in my last message, ISSX enters 2015 in a sound position thanks to prudent financial management, strong returns from invested funds over the last two years, and higher-than-forecast revenue from the extremely successful joint ISSX-JSSX meeting held in San Francisco, California, USA last October. The organization of high-quality scientific meetings is a core activity of ISSX. Two major scientific meetings are scheduled for 2015. The 13th European Meeting will be held in Glasgow, Scotland from June 22–25. The meeting co-chairs Ann Daly and Roland Wolf, together with the Meeting Organizing Committee, have assembled an excellent scientific program, which is available on the ISSX website. The meeting will be held at a new state-of-the-art conference facility at the University of Strathclyde, located in Glasgow's
city centre. Glasgow is also conveniently located to Edinburgh and other tourist destinations, including the Scottish Highlands. The 20th North American Meeting will be held in Orlando, Florida, USA from October 18-22. The full scientific program will be publicized in the ISSX Newsletter and on our website in the near future. Please attend an ISSX meeting this year and encourage your colleagues to do the same. Consistent with the Society’s objectives of increasing internationalization and expanding scientific outreach, ISSX was a sponsor of the 7th International Symposium on Drug Metabolism and Pharmacokinetics held from February 19-21 at the National Institute of Pharmaceutical Education and Research (NIPER) in Chadigarh, India. Geoff Tucker (President-elect) and Ann Daly (Councillor) represented ISSX by attending and contributing invited lectures. Owing to inclement weather in northeast USA and flight cancellations, Jim Halpert (Treasurerelect) could not attend in person, but
delivered his lecture via the internet. The Symposium was well-attended and included a lot of student attendees, many of whom gave talks and presented posters. All of the sessions were followed by lively Q&A sessions. This was a highly successful conference, forming the basis for an even closer collaboration between ISSX and Indian DMPK scientists in the future. ISSX Council continually considers initiatives to enhance member benefits and in recent months we have looked at ways of promoting the role of new investigators, both in terms of their science and input in the Society. (ISSX defines new investigators as a member who is within ten years of having earned their highest degree.) A working party, comprised of Andrew Parkinson (Treasurer) and Tom Continued on page 12
IN THIS ISSUE 1
ISSX President’s Message
3
2
Book Review: A preview of four books
4
Member Spotlight: Dr. Nina Isoherranen 20th North American ISSX Meeting
11 13th European ISSX Meeting 14 Welcome New Members
Book Review This issue’s “Book Review” features a preview of four books which will become available from the Royal Society of Chemistry in the near future:
In Silico Medicinal Chemistry: Computational Methods to Support Drug Design Author: N. Brown 360 pp., ISBN: 978-1-782-621638…2015
2
/ISSX Newsletter / Issue 1, 2015
The use of computers to aid in every aspect of the discovery, design, and development of therapeutic agents is no longer new. In fact, it would be unthinkable if assistance was not provided by such technological aids. This volume is meant to serve as a guidebook for the methodologies and theories in the expanding field of chemoinformatics, focusing on support for drug construction and then the various phases of subsequent development. The advertising literature states that the text is, “…up-to-date and written with attention to ensuring that methods are presented with clarity and the importance of their context in modern medicinal chemistry and drug design are detailed.” It should be of value to those entering, and those already within, this field. Imidazole Dipeptides: Chemistry, Analysis, Function and Effects Author: V. Preedy 330 pp., ISBN 978-1-849-738903…2015 Carnosine and its N-methylated derivative, anserine, are two imidazole dipeptides (ß-alanine and histidine) that are present in the muscle and brain tissues of mammals and birds. Their physiological importance is still being investigated, but it is known that they are antioxidants, anserine
being the more potent, and as such they are offered widely as health supplements. This planned volume will survey the current knowledge of these two compounds, and by taking an interdisciplinary approach, will delve into other areas where they may be of future therapeutic benefit. The promotional material states that, “this book will be of great interest to researchers and professionals in chemistry, food science, biochemistry, health sciences and sports sciences.” Drug Discovery for Schizophrenia Authors: T. Lipina and J. Roder 500 pp., ISBN 978-1-782-620266…2015 Since antipsychotic pharmacotherapy was established during the 1950s, there appears to have been a relative inertia in the development of new effective drugs for the treatment of schizophrenia. Only a few innovations have been made and undoubtedly much more needs to be achieved. This book intends to outline the present therapeutic strategies, discuss the underlying problems, and cover new insights in the field of schizophrenia. By bringing these issues to the forefront and presenting them to the scientific community the book aims to, “advance scientists’ and clinicians’ understanding in this area and to fuel drug discovery.” One hopes that it will succeed in its laudable objectives and stimulate further fruitful research into this apparently sluggish area. Pharmaceuticals in the Environment Authors: R. Hester and R. Harrison 250 pp., ISBN 978-1-782-621898…2016 We are amply aware that the release of pesticides into the environment causes toxicological problems
as could the use, or overuse, of agricultural fertilizers. By an equal measure, the release of pharmaceuticals and their metabolites into the environment may occur through a variety of routes during their manufacture and usage. Localized concentrations of such chemicals in waste water systems, sewage treatment plants, or even restricted tidal waters, may lead to sufficient concentrations accumulating that could produce subtle, but measurable effects. This book intends to review these problems and it states that, “pharmaceutical researchers, environmentalists and policy makers may all benefit from this title in expanding their understanding of the impacts of pharmaceuticals on the environment.”
Previewed by:
Steve Mitchell Faculty of Medicine Imperial College London London SW7 2AZ, UK
Book Ordering Information: Royal Society of Chemistry Thomas Graham House Science Park Milton Road Cambridge, UK CB4 0WF Tel +44 (0)1223 420066 Fax +44 (0)1223 420247 Email: books@rsc.org Website: www.rsc.org
USA and Canada Ingram Publisher Services Customer Service, Box 631 14 Ingram Blvd. La Vergne, TN 37086 USA Tel +1 (866) 400 5351 Fax +1 (800) 838 1149 Email ips@ingramcontent.com Website: ipage.ingramcontent.com
Member Spotlight: Dr. Nina Isoherranen By: Dr. Allen Cato, III, ISSX Newsletter Editor From the beginning of Dr. Nina Isoherranen’s story, one would not have guessed that she would become a faculty member at a prestigious university in the United States working in the pharmaceutical sciences and conducting biomedical research . . .
Isoherranen’s research in vitamin A homeostasis started with characterizing the CYP26 enzymes responsible for the metabolism of retinoic acid. Her research expanded
Continued on page 15
/ISSX Newsletter / 3
Isoherranen’s graduate studies were under the guidance of Drs. Meir Bialer and Boris Yagen at the Hebrew University in Jerusalem, Israel, where she focused on developing new antiepileptic drugs. She was involved with
Isoherranen decided to settle in Seattle because she was enthused by the collaborative environment and the multitude of scientific opportunities the University of Washington offered. In addition, Seattle was a good match for her husband, who was working on his postdoctoral research in biochemistry, and for their joint passion for outdoor activities that are just minutes away from Seattle. Isoherranen comments that while running her lab at the UW, she has worked with an “…incredibly talented and hard working group of graduate students, postdocs and visiting scientists from all over the world as well as inspiring collaborators. They have been an amazing group of people to work with and made the last ten years really exciting and rewarding.” She is also extremely grateful for the NIH and the National Institute of General Medicine for funding her research and the group over the past ten years. During this time, her research lab has focused on three principle areas of research: (1) vitamin A homeostasis and retinoic acid metabolism; (2) prediction and rationalization of complex DDIs; and (3) altered drug metabolism during pregnancy.
Issue 1, 2015
Dr. Isoherranen grew up in the small town of Kokkola, Finland (population 35,000). During her childhood, she was most interested in the arts, not so much in science: “I did acting and drama, wrote stories, played violin and piano, studied visual arts, and did plenty of sports, especially orienteering.” (Orienteering is a cross-country contest in which competitors use a map and a compass to find their way through unfamiliar territory.) She even trained rescue dogs and was part of a response team responsible for search-and-rescue operations. Along with these activities, Isoherranen managed to keep up with the math, physics, and language requirements in school: “I studied four foreign languages during school, but can only actively use two of them.” Her grades in the sciences and graduation were enough to allow her to get into the University of Helsinki in chemistry, biochemistry, and geology without being required to take the entrance exams. Her intention was to study drama and write for the theater, but one of her earliest mentors, her father, convinced her to keep these activities as a hobby and pursue a science-based professional degree. Isoherranen’s academic interests were clearly influenced by her parents, who have strong biomedical backgrounds. Her father is a veterinary pharmacologist, and her mother is a dentist and an organic chemist. Isoherranen reflects, “As a kid I participated in the clinics with my parents, and I was always aware of the interesting questions related to drug dosing in unusual populations or in different species.” During her studies at the University of Helsinki, she became enamored with mass spectrometry and completed her master’s degree in analytical chemistry with a minor in biochemistry and applied chemistry. As she continued her studies, she wanted to combine analytical chemistry with biomedical applications, and pharmacokinetics and drug metabolism seemed the perfect combination for her to focus on during her graduate research studies.
the chemical synthesis and pharmacokinetic analyses of new compounds, and the evaluation of the teratogenic potential and pharmacological activity of these compounds in various animal models. As part of these studies, Isoherranen considered it a privilege to be part of several collaborations and to get to work in three different laboratories in the United States to complete the research for her thesis. One of these laboratories was with Dr. Rene H Levy in Seattle, where she discovered her passion towards drug metabolism. It seems that her experience in orienteering paid off. After navigating her way from Helsinki to Jerusalem and several cities in the United States, she decided to work as a postdoctoral fellow in Seattle with Dr. Ken Thummel. She worked predominantly on CYP3A4, specifically on the inhibition of CYP3A4 by itraconazole, where she characterized the role of the itraconazole metabolites in drug-drug interaction (DDI) studies.
ISSX 2015 GLASGOW SCOTLAND
ISSX 2015 GLASGOW SCOTLAND
13th European ISSX Meeting University of Strathclyde Technology and Innovation Centre Glasgow, Scotland | June 22–25, 2015
On behalf of the International Society for the Study of Xenobiotics, you are warmly invited to join us at the 13th European ISSX Meeting which convenes June 22–25, 2015 13 EUROPEAN at the University of Strathclyde’s Technology and Innovation Centre in Glasgow, Scotland. ISSX MEETING TH
June 22-25, 2015
University of Strathclyde GENERAL INFORMATION Glasgow, Scotland
Reserve lodging via this web site: www.issx.org/13euro/hotel
MEETING LOCATION
University of Strathclyde Technology and Innovation Centre 13 EUROPEAN MEETING 121 George ISSX Street June 22-25, 2015 | University of Strathclyde | Glasgow, Scotland Glasgow, Scotland G1 1RD
CLIMATE/TIME ZONE
TH
ACCOMMODATIONS ISSX has arranged for special rates at several hotels in different price categories in the area near the Technology and Innovation Centre in Glasgow. The hotels are within walking distance to the meeting facility. Attendees are welcome to secure lodging at alternative venues. Reservations for hotels in our housing block will be accepted on a first-come, first-served basis. A limited number of hotel rooms are available at each property. Reservations will be accepted based upon availability up to two weeks before our meeting convenes. It is to the attendee’s advantage to reserve their hotel accommodations as soon as possible.
The month of June is characterized by gradually rising daily high temperatures, with daily highs around 17° C (63°F) throughout the month, sometimes exceeding 23° C (73°F). The daily low temperature ranges from 8° C (47°F) to 11° C (51°F). Glasgow is located in the Greenwich Mean Time zone and Daylight Savings Time will be observed at the time of the meeting.
LANGUAGE The official language of the 13th European Meeting is English. All abstracts and presentations will be in English. No simultaneous translation will be available.
For complete information about travel to Glasgow, dining, culture, sightseeing, and more, visit www.peoplemakeglasgow.com
Meeting Organizing Committee
4
/ISSX Newsletter / Issue 1, 2015
CO-CHAIRS: Roland Wolf University of Dundee, Dundee, Scotland Ann Daly Newcastle University, Newcastle upon Tyne, England
MEETING ORGANIZING COMMITTEE: John Hayes University of Dundee, Dundee, Scotland
Brian Houston University of Manchester, Manchester, England
Colin Suckling University of Strathclyde, Glasgow, Scotland
Neil Kitteringham University of Liverpool, Liverpool, England
Geoff Tucker University of Sheffield, Sheffield, England
Michael McMahon University of Dundee, Dundee, Scotland
Michael Voice Cypex, Ltd., Dundee, Scotland
Richard Meehan University of Edinburgh, Edinburgh, Scotland
Heather Wallace University of Aberdeen, Aberdeen, Scotland
Munir Pirmohamed University of Liverpool, Liverpool, England
Matt Wright Newcastle University, Newcastle upon Tyne, England
Continued on next page
SHORT COURSE DESCRIPTIONS
SHORT COURSE 3: Physiologically Based Pharmacokinetic Modelling
SHORT COURSE 1: Mass Spectrometry in Drug Metabolism Studies
Chairs: Geoff Tucker, Simcyp Limited, Sheffield, UK and Brian Houston, University of Manchester, Manchester, UK
Chairs: Neil Kitteringham, University of Liverpool, Liverpool, UK and Ian Wilson, Imperial College, London, UK
The application of physiologically based pharmacokinetic (PBPK) modelling has come of age in drug development and regulation, reflecting significant advances over the past 20 years in the predictability of key pharmacokinetic parameters from human in vitro data, especially with respect to drug-drug interactions, and the availability of dedicated software platforms and associated data bases. This course will provide an understanding of the basic principles of in vitro – in vivo extrapolation; key issues will be illustrated with specific case studies, and the special considerations necessary to extend PBPK modelling to predict paediatric drug doses will be explained. The current status of regulatory acceptance of simulations based on PBPK modelling will be discussed.
Early determination of metabolic stability and metabolic fate of compounds in drug discovery is seen as a key part of ensuring that compounds are only selected for further studies if they have properties that make them suitable for future development. The use of LC-MS is now ubiquitous by discovery teams to determine the pharmackokinetics, metabolic stability and the metabolic fate of drug candidates. This short course will illustrate how LC-MS is used to detect and identify metabolites, highlight metabolic “hot spots,” identify compounds with reactive metabolite liabilities, and enable structure optimization. SHORT COURSE 2: Stem Cell Derived Tissues in Toxicology Chairs: Chris Goldring, University of Liverpool, Liverpool, UK and Matt Wright, Newcastle University, Newcastle upon Tyne, UK
Chairs: Andy Pitt, Aston University, Birmingham, UK and Neil Kitteringham, University of Liverpool, Liverpool, UK This short course aims to provide an overview of the exciting, new, and innovative applications for mass spectrometry in the study of xenobiotics and their interactions with proteins. The interface between small molecules and biological macromolecules is at the heart of both drug efficacy and xenobiotic toxicity—mass spectrometry offers the perfect platform to explore this interface. The first three talks explore different approaches to deploy mass spectrometry within this context, whilst the final talk addresses the thorny issue of dealing with large data sets from both metabolomics and proteomic studies.
SCIENTIFIC PROGRAM
The scientific program is subject to change.
SHORT COURSE 1: Mass Spectrometry in Drug Metabolism Studies Chairs: Ian Wilson, Imperial College, London, United Kingdom and Neil Kitteringham, University of Liverpool, Liverpool, United Kingdom Continued on next page
/ISSX Newsletter / 5
SHORT COURSES
Issue 1, 2015
Current preclinical drug testing does not predict some forms of adverse drug reactions in humans. Adhering to the principles of the 3Rs, efforts at improving predictability of drug-induced tissue injury in man have included using stem cell technology to generate human cells for screening for adverse effects of drugs in man. This short course will explain the background to this area, why stem cells may be useful tools in the assessment tool-box to predict basic cellular perturbation, what we need from the cells, how to compare them with their terminally-differentiated human counterparts and what techniques are used to carry out this phenotyping. Real-world examples of how cells differentiated from stem cells are being deployed to investigate drug/chemical toxicity will be described. Four senior researchers in this field will present a background, and the following organ systems will be discussed in detail: liver, heart, and kidney.
SHORT COURSE 4: New Horizons in Mass Spectrometry
LC-MS in Metabolite Identification in High Throughput Drug Discovery Anthony Dickie, Evotec (UK) Ltd., Abingdon, United Kingdom Detecting and Identifying Reactive Metabolites Sara Amberntsson, AstraZeneca, Molndal, Sweden
SHORT COURSE 4: New Horizons in Mass Spectrometry Chairs: Andy Pitt, Aston University, Birmingham, United Kingdom and Neil Kitteringham, University of Liverpool, Liverpool, United Kingdom
The Use of LC-MS for Comprehensive Metabolite Characterisation and Identification Russell Mortishire-Smith Waters, Wilmslow, United Kingdom
New Applications of Proteomics in Biomedical Research Andy Pitt, Aston University, Birmingham, United Kingdom
Tips, Tricks and LC-ICPMS for Metabolite Detection and Identification Ian Wilson, Imperial College, London, United Kingdom
Imaging for Xenobiotics and Metabolites Malcolm Clench, Sheffield Hallam Uniersity, Sheffield, United Kingdom
SHORT COURSE 2: Stem Cell Derived Tissues in Toxicology Chairs: Chris Goldring, University of Liverpool, Liverpool, United Kingdom and Matt Wright, Newcastle University, Newcastle upon Tyne, United Kingdom
Data Independent Acquisition: A New Era for Quantitative Proteomics? Rosalind Jenkins, University of Liverpool, Liverpool, United Kingdom
The Application of Stem Cells in Toxicology: What do We Need and Why do We Need Them? Chris Goldring, University of Liverpool, Liverpool, United Kingdom Derivation of Cardiomyocytes, Stem Cells, and Toxicity Testing Chris Denning, University of Nottingham, Nottingham, United Kingdom Stem Cell-Derived Renal Cells Daniele Zink, Institute of Bioengineering and Nanotechnology, Singapore Hepatocyte Stem Cells in Toxicity Testing Matt Wright, Newcastle University, Newcastle upon Tyne, United Kingdom SHORT COURSE 3: Physiologically Based Pharmacokinetic Modelling Chairs: Geoff Tucker, Simcyp Limited, Sheffield, United Kingdom and Brian Houston, University of Manchester, Manchester, United Kingdom Use of PBPK Modelling for First in Human Dose Predictions - Incorporation of Uncertainty in Experimental Data and in-vitro in-vivo Extrapolation Strategies Michael Gertz, F. Hoffmann-La Roche, Basel, Switzerland PBPK Case Studies Karen Rowland Yeo, Simcyp Limited, Certara, Sheffield, United Kingdom Paediatric PBPK Modelling Kay Ogungbero, University of Manchester, Manchester, United Kingdom
Making Sense of the Data: How to Handle Large Proteomic and Metabolomics Datasets Karl Burgess, University of Glasgow, Glasgow, United Kingdom
SYMPOSIA
KEYNOTE ADDRESS: Protein Kinase Inhibitors: Major Drugs of the 21st Century Professor Sir Philip Cohen, University of Dundee, Dundee, United Kingdom SYMPOSIUM 1: Recent Developments in Stem Cell Technology and its Application to Drug Metabolism and Drug Safety Testing Chairs: David Hay, University of Edinburgh, Edinburgh, United Kingdom and Ludovic Vallier, University of Cambridge, Cambridge, United Kingdom Pluripotent Stem Cell Hepatocytes and Tissue Engineering David Hay, University of Edinburgh, Edinburgh, United Kingdom Pluripotent Stem Cell Hepatocytes and Cholangiocyte Models Ludovic Vallier, Wellcome Trust - MRC Stem Cell Institute, Cambridge, United Kingdom Animal Models Stephen Strom, Karolinska Institutet, Stockholm, Sweden SYMPOSIUM 2: Expanding the Boundaries of PKPD Modelling Chairs: Geoff Tucker, Simcyp Limited, Sheffield, United Kingdom and Brian Houston, University of Manchester, Manchester, United Kingdom
6
/ISSX Newsletter / Issue 1, 2015
A European Regulatory Perspective on PBPK Modelling Susan Cole, Medicines and Healthcare Products Regulatory Agency (MHRA), Slough, United Kingdom
Continued on next page
Systems Pharmacology Meindert Danhof, Leiden University, Leiden, Netherlands Modelling in Toxicity Tarjinder Sahota, GlaxoSmithKline, Uxbridge, United Kingdom Incorporating Transporter Kinetics into PBPK Models Alexandra Galetin, University of Manchester, Manchester, United Kingdom PBPK Modelling of mABs Linzhong Li, Simcyp Limited, Certara, Sheffield, United Kingdom SYMPOSIUM 3: Systems Toxicology Chairs: Paul Watkins, The Hamner Institues for Health Sciences, Research Triangle Park, NC, United States and Bob van de Water, Leiden University, Leiden, Netherlands Systems Microscopy to Unravel the Wiring of Toxicity Pathways in Drug-induced Liver Injury Bob van de Water, Leiden University, Leiden, Netherlands A Quantitative Systems Biology Analysis of Signal Transduction Networks Underlying DILI Ursula Klingm端ller, DKFZ, Heidelberg, Germany Systems Modelling Approaches to Predict Idiosyncratic DILI Paul Watkins, The Hamner Institute for Health Sciences, Research Triangle Park, NC, United States Integration of QSAR and PK-PD Modelling in Cardiac Drug Safety Assessment Sebastian Polak, Simcyp Limited, Certara, Sheffield, United Kingdom SYMPOSIUM 4: Clinical Implementation of Pharmacogenomics Chairs: Ann Daly, Newcastle University, Newcastle upon Tyne, United Kingdom and Matthias Schwab, Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany
Importance of Drug Transporter Polymorphisms and Scope for Clinical Implementation Matthias Schwab, Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany
Regulatory View Eva Gil Berglund, Medical Products Agency, Uppsala, Sweden N1-methylnicotinamide: An Endogenous Probe for Drug Interactions by Renal Cation Transporters? Martin Fromm, University of Erlangen-Nuremberg, Erlangen, Germany Predictions of Cellular Drug Binding and Implications for Intracellular Drug Concentrations and Effects Par Matsson, Uppsala University, Uppsala, Sweden Substrate/Inhibition Assays and Prediction of DDIs Christoph Funk, F. Hoffmann-La Roche Ltd., Basel, Switzerland SYMPOSIUM 6: Advances in Pathways of Chemicallyinduced Oxidative Stress and DNA Damage Chairs: John Hayes and Ken Tew Control of Redox Homeostasis by the Nrf2 Regulatory Network John Hayes, University of Dundee, Dundee, United Kingdom Regulation of Protein Function Following S-Glutathionylation Kenneth Tew, Medical University of South Carolina, Charleston, SC, United States The Redox Chemistry of Antioxidants Claus Jacob, University of Saarland, Saarland, Germany Control of H2O2 Transport in and Between Cells Roberto Sitia, University Vita Salute San Raffaele Scientific Institute, Milan, Italy SYMPOSIUM 7: Humanised Animal Models in Drug Development Chairs: Colin Henderson, University of Dundee, Dundee, United Kingdom and Frank Gonzalez, National Cancer Institute, Bethesda, MD, United States Humanised Mouse Models of Drug Metabolism Colin Henderson, University of Dundee, Dundee, United Kingdom
Continued on next page
/ISSX Newsletter / 7
Implementation of Pharmacogenomics in Clinical Practice-focus on Evidence-based Medicine and Cost-effectiveness Munir Pirmohamed, University of Liverpool, Liverpool, United Kingdom
SYMPOSIUM 5: Role of Drug Transporters: Current and Future Perspectives (an ITC Sponsored Symposium) Chairs: Donald Tweedie, Boehringer Ingelheim, Ridgefield, CT, United States and Brian Houston, University of Manchester, Manchester, United Kingdom
Issue 1, 2015
Pharmacogenomic Approaches to Treatment of Cystic Fibrosis Margareta Amaral, University of Lisbon, Lisbon, Portugal
HLA Genotype and Risk of Adverse Drug Reaction: Prospects for Clinical Implementation Martin Armstrong, UCB Pharma, Stockport, United Kingdom
Mouse Models for Elucidation of CYP2D6 and CYP2C19 Function in the Developing and Adult Brain Magnus Ingelman-Sundberg, Karolinska Institutet, Stockholm, Sweden Knockout and Humanised Mouse Models for Detoxifying Proteins Alfred Schinkel, The Netherlands Cancer Institute, Amsterdam, Netherlands Lipoprotein and Bile Acid Profiles in FRG Mice with Humanised Livers Ewa Elis, Karolinska Institutet, Stockholm, Sweden SYMPOSIUM 8: The Contribution of the Gut Microbiome to Drug Metabolism, Drug Interactions and Drug Toxicity Chairs: Heather Wallace, University of Aberdeen, Aberdeen, United Kingdom and Elaine Holmes, Imperial College London, London, United Kingdom Microbiome Metabolomics Elaine Holmes, Imperial College London, London, United Kingdom Impact of Host-microbial Interactions on Toxicokinetics of Tacrine Eric Chan, National University of Singapore, Singapore
Diet-microbiome Interactions Bernard Corfe, University of Sheffield, Sheffield, United Kingdom SYMPOSIUM 9: Epigenomics in Drug Metabolism and Disease Chairs: Richard Meehan, Institute of Genetics and Molecular Medicine, Edinburgh, United Kingdom and Jonathan Moggs, Novartis, Basel, Switzerland Epigenomics: Impact for Translational Sciences Jonathan Moggs, Novartis, Novartis Institutes for Biomedical Research, Basel, Switzerland
Genetic-Epigenetic Interactions and Implications for Genome Stability/Function Thomas Carell, Ludwig-Maximilians University, Munich, Germany Spatial Organisation of the Nucleus and Influence on Human Disease Wendy Bickmore, Institute of Genetics and Molecular Medicine, Edinburgh, United Kingdom SYMPOSIUM 10: Proteins as Targets for Covalent Modification by Xenobiotics: Therapeutic Opportunities versus Toxicological Risk Chairs: Thomas Baillie, University of Washington, Seattle, WA, United States and Kevin Park, University of Liverpool, Liverpool, United Kingdom Pharmacological, Physiological, and Pathological Consequences of Drug Bioactivation and Covalent Binding Kevin Park, University of Liverpool, Liverpool, United Kingdom Reactive Drug Metabolites and Targeted Covalent Inhibitors: A Risk-Benefit Perspective Thomas Baillie, University of Washington, Seattle, WA, United States Challenges in Developing AZD9291 – An Irreversible Inhibitor of EGFR-TKI Sensitising and Resistant Mutations in Non-small Cell Lung Cancer Peter Ballard, AstraZeneca, Cheshire, United Kingdom Inhibitors of Cathepsin C: Not Your Typical Oral Small Molecules Catherine Booth-Genthe, GlaxoSmithKline, Uxbridge, United Kingdom SYMPOSIUM 11: Predicting Human Responses During Drug Discovery and Development Chairs: Roland Wolf, University of Dundee, Dundee, United Kingdom and Peter Moldeus, Karolinska Institute, Stockholm, Sweden
8
/ISSX Newsletter / Issue 1, 2015
Regulation of Host Metabolism by the Gut Microbiome Through the Aryl-Hydrocarbon-Receptor Sven Pettersson, Nanyang Technological University, Singapore, Singapore
5hmC – Tissue Specificity and Modulation by Xenobiotics John Thomson, University of Edinburgh, Edinburgh, United Kingdom
Continued on next page
Application of in vivo Reporters for Stress Responses in Drug Development Roland Wolf, University of Dundee, Dundee, United Kingdom
Carboxylesterase 1 – Substrates, Regulation of Enzyme Activity and Pharmacogenetics Henrik Rasmussen, Institute of Biological Psychiatry, Roskilde, Denmark
Predicting Human Responses to Drugs: Challenges and Opportunities of in vitro Approaches Ruth Roberts, AstraZeneca, Stockport, United Kingdom
Plenary Session: Inflammation: Effects on Drug Metabolism and Disease Aetiology Chairs: Kathie Knights, Flinders University, Adelaide, Australia and Eddie Morgan, Emory University, Atlanta, GA, United States
Establishing Potential Safety Liabilities in Early Drug Development Bill Pennie, Takeda, Cambridge, MA, United States
Inflammatory Regulation of Human Drug Metabolising Enzymes Ulrich Zanger, Bosch Institute of Clinical Pharmacology, Stuttgart, Germany
The Application of Epigenome and Kinome-based Bioassays for Risk Assessment Ivonne Rietjens, Wageningen University, Wageningen, Netherlands SYMPOSIUM 12: Conjugating Enzymes and Hydrolases in Endogenous and Foreign Compound Metabolism Chairs: Michael Arand, University of Zurich, Zurich, Switzerland and John Miners, Flinders University, Adelaide, Australia Microsomal (and Soluable) Epoxide Hydrolase in Eicosanoid Metabolism and its Physiological Consequences Anne Marowsky, University of Zurich, Zurich, Switzerland DDIs Involving Glucuronidated Drugs John Miners, Flinders University, Adelaide, Australia Role of SULTs in Metabolic Activation Hansruedi Glatt, German Institute of Human Nutrition, Potsdam, Germany
Regulation of Drug Transporters in Inflammation: Impact on Drug Disposition Micheline Piquette-Miller, University of Toronto, Toronto, Canada Role of NO in Inflammatory Regulation of Drug Metabolising Enzymes Edward T. Morgan, Emory University, Atlanta, GA United States Inflammation and Liver Disease Percy Knolle, Technische Universität München, Munich, Germany SPECIAL KEYNOTE CLOSING LECTURE Frank Gonzalez, National Cancer Institute, Bethesda, MD, United States
Continued on next page
UPCOMING MEETINGS 13th European ISSX Meeting University of Strathclyde Glasgow, Scotland, UK June 22–25, 2015 Meeting Chairs: Roland Wolf, Ph.D. & Ann Daly, Ph.D.
11th International ISSX Meeting Busan Exhibition and Convention Center Busan, Korea June 12–16, 2016 Meeting Chair: Jae-Gook Shin, Ph.D.
Issue 1, 2015
20th North American ISSX Meeting Hilton Orlando Bonnet Creek Orlando, Florida, USA October 18–22, 2015 Meeting Chairs: Hartmut Derendorf, Ph.D. & Stephan Schmidt, Ph.D.
21st North American Meeting Rhode Island Convention Center Providence, Rhode Island September 24–28, 2017 Meeting Chair: Jashvant Unadkat, Ph.D.
/ISSX Newsletter / 9
Continued on next page
REGISTRATION INFORMATION The meeting registration fee includes admittance to: • Scientific Symposia and Special Lectures • Awards Presentation and Lectures • Poster Presentation • Poster Awards Competition Review and Awards Session • Exhibition • Civic Reception • Opening Welcome Reception The short courses are separately ticketed offerings and may be added to a registration at an additional fee. Register today at www.issx.org/13euro/register.
REGISTRATION FEES Early Regular On-Site Short Courses Through March 31, 2015 April 1–June 21, 2015 June 22–25, 2015 All Prices in US Dollars ISSX Member Nonmember Student Member Student Non-Member Meeting Registration All Prices in US Dollars
$175 $225 $100 $125
Early Regular On-Site Through March 31, 2015 April 1–June 21, 2015 June 22–25, 2015
ISSX Member Nonmember Student Member Student Non-Member Guest
$615 $775 $250 $275 $50
and all refreshment breaks. Guest registration does not include admittance to the scientific sessions or the ISSX Social Event at the Old Fruit Market. Tickets to the social event may be purchased for guests in advance.
SOCIAL PROGRAM
MEETING DINNER AND CEILIDH
Start the meeting at the Opening Welcome Reception in the exhibition and poster area of the Technology and Innovation Centre on Monday, June 22. Enjoy hors d’oeuvres and drinks while you meet with our meeting exhibitors and fellow attendees. Included with full meeting registration and guest ticket purchase.
CIVIC RECEPTION
/ISSX Newsletter / Issue 1, 2015
$715 $795 $845 $955 $275 $300 $300 $325 $50 $50
Please note: The meeting registration fee does not include access to the Short Courses nor the ISSX Social Event at the Old Fruit Market. Guest registration includes a meeting tote bag and admission to the opening welcome reception
OPENING WELCOME RECEPTION
10
$225 $250 $275 $325 $125 $150 $150 $175
The Glasgow City Council would like to welcome ISSX to Glasgow with a Civic Reception on Tuesday, June 23 at 18:30. This unique event will be held in the prestigious surroundings of the City Chambers in the Picture Gallery. The Lord Provosts of the City will be in attendance to greet delegates and welcome you to Glasgow. The City Chambers is in the very heart of Glasgow and is one of the city’s most important and prestigious buildings. A grand and imposing edifice overlooking George Square, the City Chambers is an impressive symbol of Glasgow’s political strength and historical wealth. Completed in 1888, the City Chambers has for over 100 years been the headquarters of successive councils serving the City of Glasgow. Complimentary - Advanced registration required.
Join us at the premier social event of the meeting at the Old Fruit Market of Glasgow which has kept all of its period charm, including its lofty vaulted roof, cast iron columns, balcony, and slender Victorian architecture. Attendees will enjoy a delicious buffet dinner, drinks, and a ceilidh. The word ceilidh (kay-lee) descended from the Gaelic word for “gathering” or “party”… However, these days when people think of a ceilidh, they think of a fun filled night of dancing, good music, and great company! The beauty of a ceilidh is that everyone can take part. You will be walked through the steps under the watchful eye of the professional caller who will be with you every step of the way – walking you through the moves before each dance and continuing to call out helpful hints throughout the rest of the dances. It is sure to be a wonderful time. Make plans to join us at the Old Fruit Market on Wednesday, June 24. Separate registration fee applies.
20th North American ISSX Meeting Hilton Bonnet Creek Hotel | Orlando, Florida, USA | October 18-22, 2015 Join ISSX in Orlando, Florida this October for the 20th North American Regional ISSX Meeting.
Invitation Letter On behalf of the Meeting Organizing Committee, it is our pleasure to welcome you to participate in the 20th North American ISSX Meeting that will be held October 18–22, 2015. The Meeting Organizing Committee and Symposia Chairs designed a stimulating program in a venue that is sure to foster scientific exchange, networking and collaborative discovery. In addition to the Symposia and Podium Sessions, the 20th ISSX Meeting features state of the art exhibits and interactive Poster sessions to optimize discussion and exchange of ideas. We encourage you to submit your research abstract for presentation at the 20th ISSX Meeting. The most interesting and stimulating abstract submissions will be selected for oral presentation in podium sessions. However, many past meeting participants prefer presentations at Poster Sessions where discussion among a few researchers can bring fresh insights.
•H ear from leading experts who will present cutting edge research findings • Gain recognition for presenting your work •E xpand your career options through networking and collegial interaction Last, but not to be forgotten, is the beautiful venue on the grounds of Disney World. Enjoy a little of Florida while renewing past acquaintances and meeting new colleagues at this premier entertainment attraction destination. We look forward to welcoming you in Orlando! Sincerely,
There are compelling reasons to attend the 20th ISSX Meeting in the Hilton Bonnet Creek Resort and Conference Center this October.
Hartmut Derendorf, University of Florida
/ISSX Newsletter / 11
Continued on next page
Stephan Schmidt, University of Florida
Issue 1, 2015
•P articipate in important scientific and educational sessions on drug metabolism, toxicology, pharmacology, molecular biology and related topics
President’s Message Continued from page 1
Baillie (Councillor), formulated a number of recommendations that aimed to increase the profile of new scientists at ISSX meetings and augment their role (both current and future) in the activities of the Society. Andrew and Tom subsequently sought feedback from new investigators during the course of the joint ISSX-JSSX meeting held in San Francisco. ISSX has hosted a new investigators reception at each of our scientific meetings for a number of years. Additionally, we will now encourage their input into the activities of ISSX through the direct representation of new investigators on Meeting Organizing Committees and other Society committees. A separate symposium will be included in our scientific meeting programs to specifically highlight the science of new investigators. Finally, I would like to acknowledge the contributions of members of Council who completed their terms in 2014: Richard Kim, Paul Ortiz de Montellano, and Hiroshi Yamazaki. They are replaced by new Councillors Natalie Hosea (USA), Takashi Izumi (Japan), and Jasminder Sahi (China). As always, I welcome comments, feedback and suggestions from members on any matters related to ISSX and its activities. John Miners ISSX President
MEETING ORGANIZING COMMITTEE Hartmut Derendorf (Co-Chair), University of Florida, Gainesville, Florida, USA Stephan Schmidt (Co-Chair), University of Florida, Orlando, Florida, USA Vikram Arya FDA, Gainesville, Florida, USA Reggie Frye University of Florida, Gainesville, Florida, USA Margaret James University of Florida, Gainesville, Florida, USA
R. Scott Obach Pfizer Inc., Groton, Connecticut, USA Andrew Parkinson XPD Consulting, Shawnee, Kansas, USA Amin Rostami University of Manchester, Manchester, UK Mirjam Trame University of Florida, Orlando, Florida, USA Geoff Tucker Simcyp Ltd., Sheffield, UK
ABSTRACTS We encourage all those involved in the fields of metabolism, pharmacology, toxicology, molecular biology and other related disciplines to consider submitting an abstract for a poster presentation at this meeting. This meeting will provide a wonderful opportunity to showcase work being done in a variety of areas and to network with other researchers. Abstract authors will have an opportunity to submit abstracts to the general abstract poster sessions and student authors can compete in the poster award competition open to pre- and post-doctoral students.
12
/ISSX Newsletter / Issue 1, 2015
For more information on abstract submissions, visit www.issx.org/20NA/abstracts.
HOTEL ACCOMMODATIONS AND MEETING REGISTRATION Accommodations are available at the Hilton Bonnet Creek Hotel. ISSX has arranged for a special discounted rate of $239 (plus applicable taxes). To reserve your accommodations, visit www.issx.org/20NA/hotel. Visit www.issx.org/20NA for more information on the 20th North American ISSX Meeting as it becomes available!
ISSX depends on the support of its members to help us organize our educational activities and to sustain our operations. ISSX members have access to a variety of exclusive benefits including: A Subscription to the ISSX Newsletter - Members receive a quarterly newsletter that highlights Society news, member spotlights, upcoming meetings, late breaking scientific news, and much more. Reduced Registration Fees - Members receive significant discounts on registration fees for all ISSX meetings and workshops. Abstract Presentations - Members have the opportunity to submit abstracts to present their work with other leaders in the field at ISSX meetings. Searchable Meeting Abstracts - Members may perform searches for and cite abstracts from past ISSX meetings. Networking Opportunities with other local and international leaders interested in DMPK. Society Awards Program - Only ISSX members are eligible for the prestigious Scientific Achievement Awards presented at our regional meetings. Travel Grants - Eligible members may apply for travel assistance to attend ISSX regional and international meetings. Membership Directory - Our searchable online membership directory makes connecting with fellow researchers convenient. Special Journal Subscription Discounts – Members receive special subscription discounts to multiple scientific journals. Visit www.issx.org/journals to subscribe today. Hold Office and Serve on a Committee - Holding a position of leadership in ISSX is a tremendous opportunity to serve your peers worldwide, to develop important skills, help set the work plan of a prestigious international scientific society, and be recognized as a volunteer leader of an international scientific society. Vote in ISSX Elections - Helping to choose the future leaders of ISSX sets the path of our organization and provides you the opportunity to elect those who best represent your interests.
Most of all, your membership indicates your support of our mission to advance the understanding of the interactions of medicines and chemicals with living systems and helps sustain our program of operations. Please support ISSX by renewing your membership today!
www.issx.org/renew The International Society of Xenobiotics 2025 M Street NW, Suite 800, Washington, DC, USA 20036 www.issx.org | information@issx.org | +1 (202) 367-1160
ISSX Welcomes New 2015 Members! Mohammad Alwashih
Antoine Huguet, Anses, France
Leanne Bedard, Bedard ADME-Tox Solutions, Canada
Jessica Iegre, AstraZeneca Research & Development, Sweden
Mohamed Ben-Eltriki, Vancouver Prostate Centre, University of British Columbia, Canada
Mohammed Imran, Shaheed Hasan Khan Mewati Government Medical College, India
Fredrik Bergström, AstraZeneca, Sweden
Deniz Irtem Kartal, Middle East Technical University, Turkey
Nitin Bhatia, Intas Pharmaceuticals Limited, India
Suresh Janadri, Acharya & BM Reddy College of Pharmacy, India
Bhupinder Bhoop, University Institute of Pharmaceutical Sciences, Panjab University, India
Vivek Kahale, University Department of Pharmaceutical Sciences, India
Marc-Olivier Boily, University of Montreal, Canada
Markus Keiser, University Medicine of Greifswald, Germany
Fangrui Cao
John Keogh, JPK Consulting, United Kingdom
Obioma Chikwendu, Temple University, United States Hugues de Boussac, Inserm, France Thierry Delemonte, Novartis Institute for Biomedical Research, Switzerland Iain Gardner, Simcyp, United Kingdom Nitin Ghiware, Nanded Pharmacy College, India
14
/ISSX Newsletter / Issue 1, 2015
Sanjeev Giri, Aurigene Discovery Technoligis LTD., India Divakar Goli, Acharya & BM Reddy College of Pharmacy, India Dilip Reddy Gunturu, Sri Venkateswara Veterinary University, India Vivek Gupta, Dr. B. L. Kapur Memorial Hospital, India Santosh Gursale, Institute Of Medical Sciences & Research, India Juho Hokkanen, Admescope LTD., Finland
Melanie Kießig, Charité Berlin, Germany Katerina Kubesova Sachin Laddha, Shital’s School of Scientific and Industrial Research, India Ge Lin, The Chinese University of Hong Kong, Hong Kong
Aleksandrs Odinecs, Nektar Therapeutics, United States Matthias Olbrich, Abbott Laboratories, Germany Khaled Omar Marlies Oorts, KU Leuven Drug Delivery and Disposition, Belgium Berend Oosterhuis, Solvo Biotechnology, Hungary Andrew Owen, University of Liverpool, United Kingdom Anthony Paiva, Bristol-Myers Squibb, United States Barbora Pastorkova Josef ezní ek Dan Scotcher, University of Manchester, United Kingdom Khaled Shibany, The University of Nottingham, United Kingdom Michal Šiller, Palacky University, Czech Republic Dagmara Szkolnicka, University of Edinburgh, United Kingdom Vijay Talla, Agile Healthcare, India
Ahmad Mahdavi, University of Tehran, Iran
Vinod Tiwari, Johns Hopkins University, United States
Petra Matouskova, Charles University, Czech Republic
Mirjam Trame, University of Florida, United States
Dinesh Mittal, LUVAS, India
Johanna Troberg, University of Helsinki, Finland
Darren Moss, University of Liverpool, United Kingdom Manjunatha Mudagal, Acharya & BM Reddy College of Pharmacy, India
Monica Valentovic, Marshall University, United States Lydia Vermeer, XenoTech LLC, United States
Lucie Navratilova
Helene Vermet, Sanofi, France
Sibylle Neuhoff, Simcyp, United Kingdom
Cong Wei, Pfizer, Inc., United States
Member Spotlight Continued from page 3
to evaluating the enzymes that synthesize retinoic acid, the ALDH1A and RDH enzymes, and the alterations in vitamin A homeostasis in different disease states and by xenobiotics. The research program at the moment is focused on the drug dosing and safety in pregnant women. Aside from her research activities, Isoherranen still spends time on her hobbies that have recently been much influenced by her family. She has taken up martial arts along with long-distance running all the way to marathon distance. She also has a goal of returning to training rescue dogs. “It’s a really rewarding experience and has taught me a lot about teamwork and how to develop a mutual trust and respect,” she explains. She is deeply grateful to her husband for his support for nearly 20 years. “It is great to be married to a scientist who will always understand that experiments are unpredictable and take longer than you anticipated.” She is also thankful for her two children who have had so much patience for their busy mom and who have always put things in perspective for what is really important.
ISSX CAREER CENTER Searching for experts in the field of drug metabolism, pharmacokinetics, pharmacodynamics, and other related areas? The ISSX Career Center job board is your premier resource to find skilled applicants.
•C reate your Company Profile free of charge and explain the organization and work environment in detail. •W hen your positions are advertised on the ISSX Career Center, an e-mail advertising the position is sent automatically to job seekers who have requested notifications about opportunities matching their search criteria. •B rowse résumés for free and pay only for the résumés that you select.
Post your jobs online today! When you use the ISSX Career Center, you ensure that your open positions are advertised in the right place.
Visit www.issx.org/careercenter.
Issue 1, 2015
/ISSX Newsletter / 15
ISSX Extends its Deepest Appreciation to our 2014–2015 Donors ISSX Membership Fund Glen B. Baker Rory P. Remmel Yukako Ito Jiri Hudecek James R. Gillette Award Fund John Thomas Callaghan Ronald Estabrook Award Fund Peter T. Kissinger Patrick J. Murphy Cornelius H. Borman The General Fund Philmore Robertson Lei Zhang Ronald H. Boecker Young Scientists Travel Fund George R. Tonn Dhiren R. Thakker Greg Slatter Margaret O. James James E. Patrick Aiji Miyashita Learn more about ISSX’s various donation funds at
www.issx.org/donate
Change of Address
ISSX Newsletter is published quarterly in the spring, summer, autumn, and winter. For information concerning advertising in this publication, including rates and specifications, please visit www.issx.org or contact information@issx.org.
If your mailing address, telephone, fax number, or e-mail has changed or will change, please let us know as soon as possible. You may update your contact information at any time using the online membership directory, which you can access in the Member Only section of the Web site. If you have forgotten your username and/or password, please contact information@issx.org.
Advertise with ISSX in the quarterly ISSX Newsletter. Rates and additional advertising opportunities are available at www.issx.org/advertising2015. Deadline for the submission* of material to the ISSX Office: ISSUE
MATERIALS DEADLINE
RELEASE DATE
Issue 2
May 15, 2015
June 2015
Issue 3
August 14, 2015
September 2015
Issue 4
November 13, 2015
December 2015
*
Subject to change
Editor Dr. Allen Cato, III Cato Research, LTD 6480 Weathers Place, Suite 104 San Diego, California 92121 USA Telephone: +1-858-452-7271 Fax: +1-858-452-7784 E-mail: jcato@cato.com
Advertise with ISSX The quarterly ISSX Newsletter is an online publication featuring Society updates, scientific articles of interest, book reviews, summaries of ISSX meeting proceedings, and more. This publication is designed to update the ISSX membership on the activities and events of the organization and to provide an information forum. Not only is the ISSX Newsletter promoted directly to all ISSX Members, but, as of 2012, it is also available to anyone who visits the ISSX Web site. Visit www.issx.org/advertising2015 today!