Volume 37
Issue 2, 2016
Save the Dates and Make Plans to Join ISSX at our Upcoming Meetings
2016 ISSX Workshop Sheraton Boston Hotel Boston, Massachusetts, USA October 27–28, 2016 Co-Chairs: Yingying Guo, Ph.D. and Jin Zhou, Ph.D.
14th European ISSX Meeting
21st North American ISSX Meeting
Gürzenich Köln
Rhode Island Convention Center
Cologne, Germany June 26–29, 2017 Chair: Uwe Fuhr, Ph.D.
Providence, Rhode Island, USA September 24–28, 2017 Chair: Jashvant Unadkat, Ph.D.
22nd North American ISSX Meeting
23rd North American ISSX and 35th JSSX Meeting
Palais des Congrès de Montréal
Hilton Waikaloa Village
Montreal, QC, Canada July 15–19, 2018 Chair: Jack Uetrecht, M.D., Ph.D.
Waikaloa, Hawaii, USA October 4–8, 2020 Co-Chairs: Allan Rettie, Ph.D. and Hiroshi Yamazaki, Ph.D.
IN THIS ISSUE 2 3 4
President's Message Book Review New Investigator Spotlight
5 6 8
ISSX Welcomes New Members Join ISSX in Boston this Fall 11th International ISSX Meeting: In Review
11 13 15
ISSX Bestows Prestigious Honors on Outstanding Leaders In Memoriam: John Gorrod ISSX Committees Help Advance Mission
ISSX President’s Message By Geoff Tucker, ISSX President As I write, ISSX has hosted another successful international meeting in Busan, Korea. The exciting scientific program helped the Society extend its interactions in the Asia Pacific region. At the meeting, ISSX recognized the achievements of three outstanding scientists who have contributed greatly to our understanding of the fate of xenobiotics: Dan Nebert was presented the R.T. Williams Distinguished Scientific Achievement Award, Nico Vermeulen was presented the Frederick J. Di Carlo Distinguished Service Award, and John Miners became an Honorary Member of the Society. More highlights and photos from the meeting can be found on pp.8–10 of this newsletter.
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Planning for upcoming meetings is progressing quite well. This October, ISSX will host a workshop entitled “Translating Preclinical Data to Human Clearance and Pharmacokinetics” in Boston, MA, USA. In 2017, ISSX will host the 14th European Meeting in Cologne, Germany in June and the 21st North American Meeting in Providence, RI, USA in September. Don’t forget to mark your diary!
New Committee appointments, effective this year, have been ratified and a full listing is available on p. 15 of this newsletter and on the ISSX website. On a strategic note, I am pleased to report that several new initiatives are now being implemented, including online education. In April, ISSX launched a webinar series to provide members with even more learning opportunities. The next webinar in the series will take place on July 27. R. Scott Obach will present on the biosynthesis of drug metabolites. Registration is now open and free to all members. I encourage you to participate! Another Society initiative is for Council to assemble a number of Focus Groups to serve as forums for increased interaction between members. Initially, we will be seeking to establish groups in drug discovery and development, bioanalytical sciences, regulatory science, cytochrome P450/phase I enzymes, and pharmacokinetics/ pharmacodynamics/systems pharmacology. Ultimately, we hope to expand to further areas, including environmental toxicology. We envision that these Focus Groups will serve as an important vehicle for ISSX to increase its societal impact. Each group will be led by a chair and vice-chair, appointed for two-year terms. The first round
of chairs and vice-chairs will be appointed by the President and President-Elect, with the help of Council and the Scientific Advisory Board, and elected by the ISSX membership thereafter. If you’re interested in getting involved, express your interest by visiting issx.org/ volunteer. Discussions are also underway to establish a New Investigators Subcommittee with responsibilities for moderating message boards, developing new investigator events at upcoming meetings, coordinating outreach to other new investigators, and leading social media engagement. Speaking of developments to expand the engagement of young scientists in ISSX, this reminds me that we should not forget the old guys and their contributions to the Society. Sadly, John Gorrod, who was President from 2000–2001, passed away peacefully at his home in Suffolk, England recently. John will be remembered for his colourful personality and his seminal research on the biological oxidation of nitrogen in organic molecules, especially in relation to the metabolism of nicotine. An In Memoriam article for John appears here on p. 13.
CHECK OUT THE ISSX CAREER CENTER With the ISSX Career Center, more than 1,000 jobs in industry and academia are at your fingertips! Visit issx.org/career to learn more about recently-posted jobs applicable to your expertise and set-up personalized job alerts to help you manage your career!
Book Review DRUG TRANSPORTERS: ROLE AND IMPORTANCE IN ADME AND DRUG DEVELOPMENT Editors: G. Nicholls, K. Youdim Royal Society of Chemistry 870 pp. (2 volumes), ISBN-13: 978-1-78262-867-5, 2016 The Royal Society of Chemistry (UK) has long recognized the importance of the chemical industry and the role of chemists within the pharmaceutical arena; in 2010 they launched a “Drug Discovery Series” of books to cover all aspects of drug discovery and medicinal chemistry. Forty such volumes have been published so far. As they state in their literature, “the books encourage learning in a range of different topics and provide valuable reference for scientists working outside their own areas of expertise. Books feature case studies to bring different aspects of the drug discovery process alive and they detail the fundamental science necessary for understanding through to the most up-to-date discoveries and cutting-edge technology.”
This review is to alert interested parties to the forthcoming publication of these volumes. This book will undoubtedly be of high production quality, as are the Society’s other publications, and should serve as a handbook for those wishing to understand the role of transporters in drug movement and as a reference text to access model examples and calculations required for predicting kinetic and dynamic situations.
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: rsc.org
USA and Canada Ingram Publisher Services Customer Service, Box 631 14 Ingram Blvd. La Vergne, TN 37086 USA ipage.ingramcontent.com Tel: +1-866-400-5351 Fax: +1-800-838-1149 Email: ips@ingramcontent.com
Issue 2, 2016
For release in late July this year are two volumes which may be purchased separately (Vol. 1, ISBN 978-1-78262-069-3; Vol. 2, ISBN 978-1-78262-866-8) concerning membrane transporters and their role in drug disposition. “This two volume set of books comprehensively reviews current knowledge and techniques in the transporter sciences and their relations to drug metabolism and pharmacokinetics.” The second volume particularly addresses developing technologies and the evolving understanding of the essential role of transporter systems. An idea of the contents may be gleaned from the following chapter headings: “Overview of drug transporter families and their role in drug development;” “Liver transporters and their involvement in the hepatocellular uptake and export systems of organic anions;” “Intestinal transporters;” “Kidney transporters;” “CNS transporters;” “Lung transporters;” “The use of in vitro and in silico systems for investigating transporter interactions;” “The use of transgenic and knockout in vivo systems for investigating transporter interactions;” “Modelling and simulation of transporter interactions;” “Clinical drug-drug interactions:
An industrial pharmaceutical perspective;” “Regulatory requirements;” “Labelling and drug transporters;” “Recent advances and emerging technologies;” “Bioinformatics;” “Regulation of transporters;” “Transporter pharmacogenomics;” “Transporter imaging;” and “Transporters and proteomics.”
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New Investigator Spotlight Ahmed A. Almousa, B.S.P., M.Sc., Ph.D. candidate Q: What are you currently researching/working on in your lab? A: Currently my research involves the assessment of cyclic peptides and lignans to locally modulate intestinal inflammation and cholesterol metabolism. Q: What led you to become interested in this particular field? A: I’m a practicing pharmacist who has always been fascinated with drug discovery, particularly how it begins and how it ends in the hands of consumers. Additionally, I wanted to specialize in a discipline that will directly influence humans’ lives–a goal that I thankfully reached after obtaining my pharmacy degree, my masters in pharmacokinetics, and through my current research in drug design and discovery. Q: Describe your greatest scientific contribution thus far in your research.
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A: During my Ph.D. program, we were trying to understand how lignans influence cholesterol metabolism. As this puzzled us for quite some time, we were forced to think outside the box in the experimental design and experimental execution. Luckily, we had a Eureka moment of discovering how lignans are potentially shunting cholesterol toward lysosomal degradation. This is a discovery that will hopefully shed some light on more cholesterol-lowering agents and promote a better understanding of their metabolism. Q: What do you value most about your ISSX membership?
Q: What advice do you have for other new investigators?
A: ISSX conferences are very practical when it comes to size. The Society is well-focused yet manages to maintain diversity. ISSX’s warmth facilitates making new connections and its diversity exposed me to new horizons of research that I will be adopting in the near future. Additionally, there is a culture of support and care for young investigators, a much-needed aspect with the increased challenges in research environments.
A: The search for knowledge is an endless journey, a fact that we all need to live with and use as the catalyst to wake up in the morning. If you are not feeling enough challenge, create your own challenge, embrace it and follow it wherever it takes you. Work on improving communication skills with the same passion you had when your hands landed on your first pipette or microscope. Scientific migration to areas that are scanty could be the reason for you to build your own community, your genuine ideas, and create a lifelong challenge for yourself (this is my own current challenge). This means leaving your comfort zone and going the extra mile, which will differentiate you from any standard researcher out there.
ISSX Welcomes New Members Taiki Abe, Tohoku University, Japan William Atkins, University of Washington, United States
Olga Kharchenko, Taras Shevchenko National University of Kyiv, Ukraine
Kei Nishizawa, Kanazawa University, Japan
Jung-Woo Bae, Keimyung University, Korea
Dohee Kim, Seoul National University, Korea
Yookhwan Noh, Ulsan University Hospital, Korea
Soo Hyeon Bae, The Catholic University of Korea, Korea
Dong Hyun Kim, CJ HealthCare, Korea
Motoji Oshikata, Waters Corporation, Japan
Michael Batey, Waters Corporation, United States
Eunjin Kim, Dong-A ST Research Institute, Korea
Sukanya Pandeti, CSIR-CDRI, India
Alicja Batog, BMS, United States
Sang Kyoon Kim, Laboratory Animal Center, DGMIF, Korea
Christel Brunschwig, University of Cape Town, South Africa Philip Burcham, University of Western Australia, Australia Apichaya Chanawong, Flinders University, Australia Joo Youn Cho, Seoul National University, Korea
Weixi Kong, Sanofi US, United States Eun-Young Kwak, Korea Institute of Science and Technology, Korea Bo-In Kwon, Korea Institute of Oriental Medicine, Korea Sookie La, BioCore Co., Ltd., Korea
Saki Noguchi, Keio University, Japan
Jeong-Eun Park, Kyungpook National University, Korea Wan-Su Park Ramakrishna Rachumallu, Central Drug Research Institute, India Colin Ross, University of British Columbia, Canada Chaelim Ryu, Dong-A ST Research Institute, Korea
Kyunghee Cho, BioCore Co., Ltd., Korea
Choong Hwan Lee, Konkuk University, Korea
Chang Seon Ryu, Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Germany
Eun Joo Choi, Chosun University, Korea
Dae Young Lee, Dong-A ST Research Institute, Korea
Raul Salazar, Universidad Autónoma de San Luis Potosí, Mexico
Hyeon Gwan Choi, Sungkyunkwan University, Korea
Jimin Lee, Korea
Hideyuki Sato, University of Shizuoka, Japan
Jae Youg Chung
Sangkyu Lee, Kyungpook National University, Korea
Kate Comstock, ThermoFisher Scientific, United States
Sun Kyung Lee, Korea University, Korea
Feng Deng
Wooin Lee, Seoul National University, Korea
Nikhilesh Dhuria, Aurigene Discovery Technologies, Ltd., India Ayano Fukuhara, Nippon BoehringerIngelheim Co., Ltd., Japan
SungWoo Hyung, Korea Hyeon-Uk Jeong, Dong-A ST Research Institute, Korea
Seong Eun Jin, Korea Institute of Oriental Medicine, Korea Sun Koung Joung, BioCore Co., Ltd., Korea Yuki Katagiri, Sumitomo Dainippon Pharma Co., Ltd., Japan
Mirei Takahashi, University of Shizuoka, Japan Shotaro Uehara, Showa Pharmaceutical University, Japan Dmitriy Ushakov
Donald McKenzie, Covance, United States
Yan Wang, DartNeuroScience, LLC, United States
Andrew McLachlan, University of Sydney, Australia
Mihi Yang, Sookmyung Women's University, Korea
Rod Minchin, University of Queensland, Australia
Hye Jin Yoon, BioCore Co., Ltd., Korea
Kim Mitchell, Scottsdale Community College, United States
Rika Yuliwulandari, YARSI University, Indonesia
Petr Mlejnek, Palacky University Olomouc, Czech Republic
Jiajia Zhao, Sichuan University, China
Masashi Nagata, Tokyo Medical and Dental University, Japan
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Yoo-Seong Jeong, Seoul National University, Korea
Ilka Maschmeyer, TissUse GmbH, Germany
Kwang-Hee Shin, Kyungpook National University, Korea
Issue 2, 2016
Ye Ran Hwang, BioCore Co., Ltd., Korea
Yong Kyu Lee, Korea National University of Transportation, Korea
Hyun-Joo Shim, Dong-A ST Research Institute, Korea
Join ISSX in Boston This Fall Translating Preclinical Data to Human Clearance and Pharmacokinetics Join ISSX this fall for an intense and engaging two-day workshop, October 27–28, 2016 in Boston, Massachusetts, USA! Pharmaceutical scientists, academicians, and regulatory professionals interested in learning about prediction approaches, developing their expertise, and gaining a more complete appreciation of using a model-based approach to better understand predicting PK/clearance are encouraged to attend this workshop. A poster session will highlight cutting-edge methodologies in human PK/clearance prediction.
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WORKSHOP OVERVIEW
Our ability to accurately predict human clearance and pharmacokinetics (PK) is a critical component of drug discovery and development. These predictions impact projection of first human dose and potential for drug-drug interactions, which are important attributes of the riskbenefit assessment framework for candidate selection and the planning of early clinical studies. Furthermore, consideration can be given to the need for dose adjustment in patients vs. healthy volunteers and for special populations such as pediatric, hepatic or renallyimpaired, and genetic subpopulations. Predictions can be challenging as a result of potential in vitro-in vivo discrepancies and inter-species differences in the specificities and abundance of enzymes and transporters. Moreover, new challenges for human PK/clearance prediction continue to arise. For example, CYP-mediated clearance is being reduced by chemical manipulation in drug discovery only to be replaced by clearance by drug metabolizing enzymes with which we have less scaling experience. This workshop aims to provide fundamental knowledge on current approaches, examine the utility of in vitro and in vivo experimental systems, discuss modeling approaches in human PK/clearance prediction, focus on the current challenges, and offer next steps. The ultimate goal is to facilitate formulation of practical strategies utilized in the pharmaceutical industry for human PK/ clearance prediction based on in vitro and animal data, in combination with modeling methods.
with physiologically-based models, to address clearance prediction for low clearance and highly bound compounds • Address challenging issues and next steps in PK/ clearance prediction for non-CYP enzymes, including UGTs, aldehyde oxidase, and carboxylesterases • Discuss approaches to predict human hepatobiliary transporter-mediated clearance • Examine experimental and modeling/simulation approaches in predicting PK/clearance in special populations for compounds of different BDDCS categories
WORKSHOP ORGANIZING COMMITTEE Yingying Guo, Co-Chair, Eli Lilly and Company Jin Zhou, Co-Chair, Boehringer Ingelheim Aleksandra Galetin, University of Manchester Stephen D. Hall, Eli Lilly and Company Donald Tweedie, Merck
CALL FOR 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. This workshop will provide a wonderful opportunity to showcase work being done in a variety of areas and to network with other researchers. View the abstract submission guidelines at issx.org/workshop/abstracts and submit an abstract for consideration by Wednesday, August 17, 2016.
SCIENTIFIC PROGRAM* *Program is subject to change.
Wednesday, October 26
Industry-Sponsored Symposia and Hosted Reception Key objectives include: •U pdate the current status and challenges in prediction of human PK • Assess the application and regulatory perspectives of PBPK modeling • Examine state-of-the-art in vitro technologies, combined
Thursday, October 27
Session 1: Short Course: Introduction to Fundamentals and Challenges in Human PK/Clearance Prediction Chair: Yingying Guo, Eli Lilly and Company Continued on next page
Predicting in vivo Clearance of Drugs from in vitro Data: Where Are We and Where Are We Going? Jashvant Unadkat, University of Washington
Predicting and Verifying Transporter-based Systemic and Tissue PK of Drugs Using Proteomics and PET Imaging Jashvant Unadkat, University of Washington
Pathways toward Human Clearance Prediction: Better Tools, Fewer Rules Daniel Mudra, Eli Lilly and Company
Session 5: Human PK/Clearance Prediction in Special Populations Chair: Jack Cook, Pfizer, Inc.
Physiologically-based Pharmacokinetic (PBPK) Modeling to Support Decisions in Drug Development Ping Zhao
Case Studies Showing Application of PBPK Modeling for Prediction of PK in Patients with Hepatic and Renal Impairment Karen Rowland Yeo, Certara
Session 2: Methodological Aspects of Clearance Prediction for Low Clearance and Highly Bound Compounds Chair: Jin Zhou, Boehringer Ingelheim Prediction for Low Clearance Compounds: Challenges and State-of-the-Art Tools R. Scott Obach, Pfizer, Inc. Prediction of Volume and Intracellular Concentrations for Highly Protein Bound Compounds Using Traditional and Novel PBPK Framework Swati Nagar, Temple University Session 3: Predicting Non-CYP Metabolizing Enzymes Mediated Clearance Chair: R. Scott Obach, Pfizer, Inc. Prediction of Hepatic and Extrahepatic UGT-mediated Clearance and Corresponding Drug-drug Interaction Risk within PBPK Paradigm Aleksandra Galetin, University of Manchester How to Use in vitro and Computational Data to Estimate Clinical Outcomes for Aldehyde Oxidase Jeff Jones, Washington State University Application of in vitro and Animal Approaches to Predict Clearance Mediated via Carboxylesterases Li Di, Pfizer, Inc. Welcome Reception with Exhibitors
Friday, October 28
Evaluation of Preclinical Animal Models to Bridge the Translational Gap for Predicting Hepatic Transporter-mediated PK and DDIs Xiaoyan Chu, Merck
REGISTER TO ATTEND
Visit issx.org/workshop/register to reserve your seat at this exciting workshop. Registrant Type
Price (USD)
ISSX Member
$615
Student/Predoctoral ISSX Member
$275
Non-Member
$775
Student/Predoctoral Non-Member
$375
RESERVE YOUR ACCOMMODATIONS
The Sheraton Boston Hotel is a contiguous part of the landmark Prudential Center/Copley Place Complex. The hotel is located just four miles from Boston Logan International Airport and under one mile from the Boston Back Bay (BBY) Amtrak Station. ISSX Workshop attendees are eligible to receive the exclusive rate of $265 USD/night, exclusive of taxes. To reserve your room, please visit starwoodmeeting.com/ Book/ISSX16 online or contact the Sheraton Hotel by telephone at +1-866-716-8134. The attendee rate is subject to availability and will not be offered after Wednesday, October 5, 2016.
EXHIBIT OR SPONSOR
You’re invited to advance your brand and raise your company’s profile by supporting this important and timely scientific workshop. Both exhibit and sponsorship opportunities are available. Visit issx.org/workshop/ exhibit to learn more.
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Utility and Challenges of in vitro Systems and Modeling Approaches in Prediction of Biliary Clearance Kim Brouwer, University of North Carolina
Role of Pharmacogenetics-based Mechanistic Modeling in Early and Late Phase Clinical Studies Manuela Grimstein
Issue 2, 2016
Session 4: Quantitative Assessment of Hepatobiliary Transporter-mediated Clearance Chair: Aleksandra Galetin, University of Manchester
PBPK Model Extrapolation to Pediatric Population: Querying Uncertainty, Defining a Role for Experimentation, and Current Practices Andrea Edginton, University of Waterloo
11th International ISSX Meeting: In Review More than nine hundred scientists, students, and exhibitors gathered at the Busan Exhibition and Convention Center in Busan, Korea this June for the 11th International ISSX Meeting. The meeting was chaired by Professor Jae-Gook Shin of Inje University College of Medicine in Busan, Korea. Professor Shin and the Meeting Organizing Committee, International Scientific Advisory Board, and Local Advisory Board developed an impressive scientific program that showcased ADME in new drug development within the theme of “The Science of Xenobiotics in the Era of Personalized Medicine.” More than 75% of attendees were from the Asia Pacific region, but ISSX also welcomed attendees from North America, Europe, and Africa. The meeting was preceded by four short courses attended by 300 meeting registrants. The courses consisted of ADME Characterization of Biologics and Antibody Drug Conjugates (ADCs); Principles of In Vitro-In Vivo Extrapolation in the Application of PBPK Modelling; Drug-induced Liver Injury – How Mechanistic Insights Aid Preclinical Detection and Prediction; and Modelling Approaches to the Prediction of Drug-drug Interactions. The meeting formally commenced with an impressive opening ceremony featuring dancers and a drum performance followed by a keynote lecture on drug transporters from Professor Yuichi Sugiyama (RIKEN,
Japan). Afterwards, attendees were invited to an Opening Welcome Reception to network and visit with the many companies exhibiting their products and services at the meeting. The scientific program reflected the extraordinary breadth of the field of xenobiotics with timely symposia and daily plenary sessions. The program also featured a special Asia-Pacific regional session which highlighted significant contributions from Asia-Pacific scientists. Poster networking and presentation sessions were held throughout the meeting and provided 295 authors with the opportunity to present their research on an international stage. Attendees were invited to participate in a robust social program that included a banquet dinner at the Bay 101 Yacht Club on beautiful Haeundae Beach and a new investigators networking reception for students and postdoctoral scientists still in training. Attendees took advantage of an afternoon free of scientific programming on Tuesday, June 14 to explore the rich culture and natural beauty of “Dynamic Busan.” Throughout the meeting, attendees could make plans to attend tours to many geographical and cultural sights including the Oryukdo Islands and Beomeosa Temple, one of the three major temples in Korea.
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View all of the Meeting Photos at ISSX.SMUGMUG.COM
The R.T. Williams Distinguished Scientific Achievement Award is presented to Daniel W. Nebert, M.D. (From Left to Right: Jae-Gook Shin, Charles Crespi, Daniel Nebert, Tom Baillie, and Geoff Tucker).
The Frederick J. Di Carlo Distinguished Service Award is presented to Nico P.E. Vermeulen, Ph.D. (From Left to Right: Jae-Gook Shin, Nico Vermeulen, Tom Baillie, and Geoff Tucker). Continued on next page
This meeting featured the presentation of two prestigious Society awards. The R.T. Williams Distinguished Scientific Achievement Award, sponsored by Charles Crespi and Family, was awarded to Daniel W. Nebert, M.D., Professor, Department of Environmental Health, University of Cincinnati Medical Center and Professor, Department of Pediatrics Division of Human Genetics, Children’s Hospital Medical Center, Cincinnati, OH, USA. The Frederick J. Di Carlo Distinguished Service Award was awarded to Nico P.E.
Vermeulen, Ph.D., Professor of Molecular Toxicology, Vrije Universiteit, Amsterdam, the Netherlands. Learn more about ISSX’s 2016 award winners on pp. 11–12.
Attendees visit with exhibitors during Sunday’s Opening Welcome Reception.
Attendees learn from one another during a poster networking session at the meeting.
The Society is grateful to Meeting Chair Professor Jae-Gook Shin, the organizing committees, session chairs, speakers, exhibitors, sponsors, and attendees who made this meeting possible.
Attendees take a break from scientific sessions to enjoy sightseeing tours.
Issue 2, 2016
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The meeting’s social events featured several live performances, including a surprise from Meeting Chair Jae-Gook Shin—he plays the ukulele!
YOU CAN STILL ATTEND AN ISSX EVENT IN 2016 Were you unable to join ISSX in Busan, Korea? Make plans to attend ISSX's fall workshop, October 27–28, 2016 in Boston, MA entitled, “Translating Preclinical Data to Human Clearance and Pharmacokinetics.” This two-day workshop features well-known speakers from industry, academia, and regulatory agencies and will address critical challenges in predicting human clearance and pharmacokinetics. Learn more about this workshop on pp. 6–7.
POSTER AWARDS COMPETITION
11th International ISSX Meeting Poster Award Winners (From Left to Right): ISSX President Geoff Tucker, Shiyan Chen, Lin Zhu, Michelle Schaefer, Ilka Maschmeyer, Poster Awards Committee Co-Chair R. Scott Obach, and ISSX President-Elect Tom Baillie. ISSX encourages high-quality research and recognizes distinguished poster presentations by young scientists in both the graduate/predoctoral and postdoctoral categories during the meeting. All posters accepted as finalists in the competition were reviewed and rated by the Poster Awards Committee on the basis of Significance of the Research Problem; Experimental Approach; Soundness of Conclusions; and Clarity of Presentation. The award recipients were:
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GRADUATE/PREDOCTORAL AWARDS FIRST PLACE: Taiki Abe of the Graduate School of Pharmaceutical Sciences, Tohoku University in Japan for the poster A6 entitled “PXR Stimulates the Growth Factor-Mediated Hepatocyte Proliferation by Inhibiting FOXO-Mediated Transcription of Cell Cycle Suppressor Genes” SECOND PLACE: Michelle Schaefer of Boehringer Ingelheim Pharma GmbH & Co. KG in Germany for the poster A4 entitled “Metabolic Capability of Upcyte Human Hepatocytes in Long-Term Sandwich Culture and Utility for Clearance Prediction” THIRD PLACE: Shiyan Chen of the National University of Singapore for the poster A5 entitled “Comparison
of the Inhibitory Effects of Selective Estrogen Receptor Modulators, Tyrosine Kinase Inhibitors, and Steroidal Drugs on Human Aldehyde Oxidase Activity”
POSTDOCTORAL AWARDS FIRST PLACE: Ilka Maschmeyer of TissUse GmbH in Germany for the poster A11 entitled “Multi-Organ-Chip Developments: Towards a Paradigm Shift in Drug Development” SECOND PLACE: Lin Zhu from the School of Biomedical Sciences, The Chinese University of Hong Kong in China for the poster A8 entitled “Toxicokinetic Study of Pyrrolizidine Alkaloid-Derived DNA Adducts, the Potential Biomarker of Pyrrolizidine Alkaloid-Induced Tumorigenicity” THIRD PLACE: Min Gi Kim of Sungkyunkwan University in Korea for the poster A12 entitled “Development of a Physiologically Based Pharmacokinetic Model for Benzyl Butyl Phthalate and its Active Metabolites, Mono Benzyl Phthalate and Mono Butyl Phthalate, in Rats” Congratulations to all of the graduate/predoctoral and postdoctoral award finalists and winners.
ISSX Bestows Prestigious Honors on Outstanding Leaders THE R.T. WILLIAMS DISTINGUISHED SCIENTIFIC ACHIEVEMENT AWARD Sponsored by Charles Crespi and Family The 2016 R.T. Williams Distinguished Scientific Achievement Award is presented to an ISSX member or non-member from any region who has made substantial and seminal scientific contributions to the field over a sustained period. The focus of this award is the individual's scientific accomplishments and it is intended to recognize the best in the field internationally. The 2016 recipient is Daniel W. Nebert, M.D., Professor, Department of Environmental Health, University of Cincinnati Medical Center and Professor, Department of Pediatrics Division of Human Genetics, Children's Hospital Medical Center, Cincinnati, OH, USA.
•E stablishing a unique assay to study regulation of Aryl Hydrocarbon Hydroxylase enzyme activity by various compounds. This assay, performed by Dr. Nebert while working with Harry Gelboin at the NIH, has been used extensively in the study of molecular regulation by polycyclic aromatic hydrocarbons (PAH). • T he biochemical characterization of the Aryl Hydrocarbon Receptor (AhR). Working with Alan Poland and Allen Okey, a series of experiments using genetically-defined mouse models demonstrated that AHH activity was either sensitive or resistant to PAH exposure allowed the operational definition of a PAH receptor. His efforts were seminal in defining the existence of this biochemical entity. •C oncentrated effort to characterize and define the CYP1 sub-family of monooxygenases in the mouse. His efforts to study the downstream targets of the AhR was largely due to the effort of the Nebert laboratory, including the CYPs, UDP-glycosyltransferases, NAD(P)H:quinone oxidoreductase, and aldehyde dehydrogenase Type 3. This effort was followed by a series of studies to obtain the gene sequence of these proteins and study the molecular regulation of these genes. • I nfluencing the establishment of a standard nomenclature for the CYPs when other biochemical or biophysical markers did not allow a systematic mechanism for naming these heme proteins. He had considerable influence in extending the gene nomenclature for other foreign compound metabolizing enzymes.
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To recognize and celebrate Dr. Nebert’s substantial and sustained scientific contributions to the field of xenobiotic disposition spanning more than five decades, he is awarded the 2016 R.T. Williams Distinguished Scientific Achievement Award.
Issue 2, 2016
Dr. Nebert has had a long and distinguished career in foreign compound metabolism and their effects on biological systems. He has had a major impact on the direction of the research in the area encompassing the interests of ISSX. His contribution to the field of xenobiotics includes authorship of more than 645 papers and an h-index of 109. His research interests include genes encoding drug-metabolizing enzymes; CYP1A1 gene; ecogenetics; standardized gene nomenclature; gene superfamilies; human Ah receptor gene; environmental toxicology; teratology; and cancer research. Dr. Nebert’s research discoveries have resulted in hundreds of laboratories adding to the increased understanding of all endogenous functions of AHR, lipid-mediator-controlled critical life processes, and how these are affected by alterations in the AHR-CYP1 axis. These studies have resulted in thousands of publications and more than 800 review articles.
Dr. Nebert has had a major impact in the direction of the research in the area encompassing the interests of ISSX including:
THE FREDERICK J. DI CARLO DISTINGUISHED SERVICE AWARD The 2016 Frederick J. Di Carlo Distinguished Service Award is presented to an ISSX member from any region with an illustrious record of important service to the Society and its goals. The 2016 recipient is Nico P.E. Vermeulen, Ph.D. Professor Vermeulen has a long and distinguished career in drug metabolism and toxicology and he has been associated with ISSX since its founding in 1981. He has served on numerous ISSX committees and he has been intensively involved with the Society. Professor Vermeulen was first elected to the ISSX Council in 1991 and served until 1996. He ran for and was elected President-Elect in 2001 and became the President of ISSX in 2002. He continued service to the Society as Past President and member of Council and Chairman of the ISSX Nomination Committee. Professor Vermeulen has organized many international courses and meetings in the field of Drug Metabolism and Toxicology including the 3rd International ISSX meeting on Drug Metabolism in Amsterdam (1991), the International ISSX workshop on Glutathione S-transferases in Noordwijkerhout (1995), the ISSX Meeting at the Pharmaceutical Sciences Fair in Nice, France (2005),
and recently the joint 19th MDO / 12th ISSX European Meeting in Noordwijk (2012). His dedication and efforts have served to build bridges to related societies, such as the ESBP and MDO, and to many scientists worldwide. As Professor of Molecular Toxicology at Vrije Universiteit Amsterdam, he has help pioneer a new scientific discipline by introducing state-of-the-art techniques in computational chemistry and drug bioanalysis into the field of drug and chemical toxicology. He has brought his enthusiasm and scientific knowledge to the teaching and training of several generations of students. One of his most notable achievements has been turning a descriptive science into one that is predictive with respect to new molecules and human biochemistry. This work is important for the pharmaceutical industry and for the chemical industry and will have impact on the discovery and development of safer molecules. He has trained and mentored a large cohort of Ph.D. students and postdoctoral fellows, many of whom have gone on to develop distinguished, independent research careers. Professor Vermeulen’s scientific contributions have been recorded in over 400 peerreviewed papers and have been recognized by many distinguished scientific awards. For his active involvement, leadership, expertise, contributions, and commitment, ISSX is proud to honor Professor Nico P.E. Vermeulen with the 2016 Frederick J. Di Carlo Distinguished Service Award.
JOIN THE ISSX NEW INVESTIGATOR FORUM
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Have you joined ISSX’s New Investigator Forum? The forum was established to encourage new investigators to network and share ideas, research, photos, and more! Please visit issx.org/group/newinvestigators and sign in with your ISSX username and password to join the Forum and to learn more. We encourage you to leave feedback on what features you would like to see and how ISSX can better serve graduate students and recent postdocs.
INTERESTED IN PURCHASING THE ISSX MAILING LIST? ISSX membership mailing lists may be purchased through Infocus Marketing. The ISSX member and buyer postal list contains more than 35 unique sub-selects in areas of interest, allowing you to specifically target the exact audience you want to reach. For more information on pricing and specifications, please visit infocusmarketing.com/ lists/issx or e-mail Infocus Marketing at sales@infocusmarketing.com.
In Memoriam: John Gorrod By John Cashman, ISSX Member It is with a heavy heart that I report Professor John Gorrod passed away on November 14, 2015. John William Gorrod was born on October 11, 1931 in London. He was the son of Ernest Lionel and Carrie Rebecca (Richardson) Gorrod. John married Doreen Mary Collins on April 3, 1954. They had three children: Julia Caroline, Simon Jonathon William, and Nicholas Ernest Freeman. John’s wife Doreen passed away in 2012 and he is survived by his children and his grandchildren. John started his career in the early 1960s as a technician at the Chester Beatty Research Laboratories at the Institute of Cancer Research in London working for Eric Boyland. In the mid-1960s, Professor Arnold Beckett, a leader of the study of metabolism of nitrogencontaining drugs, invited John to undertake research for a Ph.D. in the Department of Pharmacy, Chelsea College (now King’s College) in London. In recognition of his research in drug metabolism, John was appointed Reader in 1980 and Professor of Biopharmacy in 1984. John eventually became Head of the Department of Pharmacy and Research Professor of King’s College in London. In recognition of his contribution to pharmacy and the pharmaceutical sciences, he was made an Honorary Member of the Pharmaceutical Society. Thereafter, he was an elected member of the Athenaeum, followed by the award of Fellow of King’s College and a Fellow of the School of Pharmacy. After retirement from his academic career at King’s College, John was offered an Emeritus Professorship at The University of Essex, where he continued his training of Ph.D. students and research.
EDUCATION Diploma, Chelsea College, London, 1961; Doctor of Philosophy, London University, 1979; Doctor of Science, London University, 1982.
CAREER Technology officer at the Chester Beatty Research Institute, London, 1955-1965; Research Fellow of Biochemistry, University of Bari, Italy, 1964; Research Fellow, Royal Commission Exhibition of 1851, 1965-1967. Lecturer in Biopharmacy, Chelsea College, London, 1968–1980; Reader in Biopharmacy, 1980–1984; Professor, Head of the Department of Pharmacy, King's College, 1984–1990; Head, Division of Health Sciences Faculty of Life Science, 1988, 1989; Research Professor, 1990–1997; Professor Emeritus, 1997; Elected Fellow, since 1996; Professor of Toxicology, University Essex, England, since 1997. Director of Drug Control and Teaching Center, Sports Council, 1985-1991; Visiting Professor, University of Bologna, University of Bari, University of Kebangsan, Malaysia, Chinese Academy of Preventive Medicine, 1991; Canada Medical Research Council Visiting Professor, University of Manitoba, University of Saskatchewan, 1988.
Advisory Council Tobacco Science and Health Institute of Science and Health, St. Louis, MO; Science Advisory Board, Philip Morris International, since 2006. Continued on next page
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President of the International Society for the Study of Xenobiotics, 2000–2001.
Issue 2, 2016
John’s research focused on the metabolism of aromatic and aliphatic amines and their N-oxides and/or hydroxylamines. This work continued throughout his career. Over John’s long career, he supervised many Ph.D. students (some of whom were pharmacy-trained), and together, they made significant contributions to the understanding of organic nitrogen atom oxidation. Many of his students assumed senior positions in academia. John published over 200 scientific papers and a dozen books including: Drug Metabolism in Man (1978); Drug Toxicity (1979); Testing for Toxicity (1981); Biological Oxidation of Nitrogen in Organic Molecules (1985); Biological Oxidation of Nitrogen (1978); Metabolism of Xenobiotics (1988); Development of Drugs and Modern Medicines (1986); Molecular Basis of Human Disease (1989); Molecular Basis of Neurological Disorders and Their Treatment (1991); Nicotine and Related Tobacco Alkaloids: and Absorption, Distribution, Metabolism and Excretion (1993); Analytical Determination of Nicotine and Related Compounds and Their Metabolites (Editor with Peyton Jacob III, 1999).
Although John was driven by his work in research, it is the warmth of the man that all who came in contact with him will remember. The time he took to mentor and motivate his students and his drive to initiate and complete research studies is well-remembered. He maintained a close network with his former Ph.D. students. His students not only learned about science, but also learned about his philosophy on life. To quote Goethe, as John often did: “Knowing is not enough; we must apply. Willing is not enough; we must do.” John did more than most to mentor students and many lives have been enriched by his friendship.
Fellow, Pan-Hellenic Association Pharmacists (Honorary); Turkish Pharmaceutical Society (Honorary); Royal College of Pathologists; Royal Society of Chemistry; Institute of Biology; Member, International Society for the Study of Xenobotics (President 2000-2001); School of Pharmacy, University of London (Honorary) Fellow; Pharmaceutical Society of Great Britain (Honorary); German Pharmaceutical Society (Correspondent); Athenaeum Club.
CALLING ALL NEW INVESTIGATORS! Are you an ISSX Student Member or Regular Member within the first ten years of receiving your highest earned degree? Would you like to be featured in ISSX Newsletter’s New Investigator Spotlight? We’d love to hear from you! Please contact ISSX at information@issx.org to indicate your interest in participating in this new opportunity.
INCLUDE ISSX IN YOUR SUMMER PLANS... Register for one of two webinars on July 27! R. Scott Obach of Pfizer, Inc. will present on Biosynthesis of Drug Metabolites for Use in DMPK Experiments and Late-Stage Lead Diversification. Webinars are a benefit of membership in ISSX and allow you to supplement your learning throughout the year. Space is limited, so reserve your spot today.
XenoTech Scientists Present Key Drug Transport Research Publishes Paper, Presents Webinar & Poster Evaluating Ketoconazole and its Alternative Clinical CYP3A4-5 Inhibitors
Sekisui XenoTech scientists have published a paper evaluating Ketoconazole and its alternative clinical CYP3A4-5 inhibitors as inhibitors of drug transporters, and have just presented their research during a webinar and with a poster that can be accessed at xenotech.com.
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The paper, authored by Sekisui XenoTech scientists Lydia M.M. Vermeer, Caleb D. Isringhausen, Brian W. Ogilvie, and David B. Buckley, evaluates the in vitro effects of Ketoconazole, Ritonavir, Clarithromycin and Itraconazole on 13 clinically-relevant drug transporters: “Ketoconazole is known to be a strong CYP3A4/5 inhibitor, and until recently, was utilized in this role in clinical drug-drug interaction (DDI) studies. Unfortunately, ketoconazole has also demonstrated the ability to cause sporadic liver injury or adrenal insufficiency. Due to this, the FDA and EMA recently recommended the suspension of ketoconazole use in DDI studies and suggested the use of alternatives such as itraconazole or clarithromycin. While the effect on CYP3A4/5 function by these compounds is well established, the known effect on drug transporters is limited. The purpose of this study was to determine the inhibitory effects of ketoconazole, clarithromycin, ritonavir, itraconazole...”
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Continue reading, watch the webinar, view the poster or learn more about at Sekisui XenoTech’s Drug Transport Contract Research Services at www.xenotech.com.
ISSX Committees Help Advance Mission The important work of the ISSX Council is supported through the efforts of several committees. The committees of ISSX are structured with staggered terms so that any one committee’s composition does not fully turnover in any given year. Committee seats recently vacated by outgoing members were filled by appointment by ISSX President Geoff Tucker and subsequently voted on by the ISSX Council. The only exception to this is the Nomination Committee whose members are elected by the Society’s membership per the bylaws.
ISSX members bring their time, talents, and insights to their terms of committee service. This service often progresses unnoticed amongst members and other constituents of the Society. Therefore, we wish to recognize our new and returning committee members and thank them for supporting our goals and helping advance the work of the Council. Our valued committee members along with the major functions of each committee are listed below. For complete information concerning the charges and responsibilities of our committees, please visit issx.org/committees.
AWARDS COMMITTEE Name
Region
Country
Tom Baillie, Chair North America United States Per Artursson Europe Sweden Fred Guengerich North America United States J. Brian Houston Europe United Kingdom Andrew McLachlan
Asia Pacific
Australia
Emily Scott
North America
United States
Ikumi Tamai
Asia Pacific
Japan
Primary Duties: • Review nominations for Society awards for recommendation to the ISSX President • Provide slides and text for the presentation of awards at Society meetings and for publication in the newsletter and on the website • Identify sponsors for awards and review other proposals for awards/honors • Review proposals for meeting dedication and provide feedback and suggestions, if appropriate, to Meeting Organizing Committees (MOCs) and Council • Liaise with MOCs to ensure that award presentations are satisfactorily integrated into meeting programs
COMMITTEE ON REGULATORY AFFAIRS Name
Region
Country
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Primary Duties: • Recommend symposium, workshop, and/or short course topics and speakers that are relevant to regulatory issues to MOCs • Maintain an interface with MOCs and the Scientific Affairs Committee to ensure that regulatory issues are considered in program development • Advise Council as to how ISSX can raise its profile among regulatory agencies and expand membership among individuals with an interest in regulatory matters Continued on next page
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J. Greg Slatter, Chair North America United States Eva Gil Berglund Europe Sweden Takashi Izumi Asia Pacific Japan Charlene McQueen North America United States Qing-li Wang Asia Pacific China Lei Zhang North America United States
FINANCE COMMITTEE Name Region Country Andrew Parkinson, Chair North America United States James Halpert, Treasurer North America United States Sonia de Morais, Treasurer-Elect North America United States Paul Hollenberg North America United States Pat Murphy North America United States Chandra Prakash
North America
United States
Primary Duties: • Regularly review the Society’s financial reports and monitor financial performance • Work with ISSX staff to prepare and present an annual budget to Council • Advise on the financial management and planning of the Society, including strategic investments and trends in expenses and revenue • Interface with MOCs to provide financial input and guidance
NOMINATION COMMITTEE Name Region Country John Miners, Chair Asia Pacific Australia Elizabeth Gillam Asia Pacific Australia J. Brian Houston Europe England Hiroyuki Kusuhara Asia Pacific Japan Edmund Maser Europe Germany R. Scott Obach
North America
United States
Primary Duties: • Select candidates from among ISSX members who consent to run for election for Officer, Councilor, and the Nomination Committee positions • Ensure that the slate of candidates for elections (Officers, Council, and Nomination Committee) is representative of the broader ISSX membership, including, but not limited to, geographical region and affiliation (i.e. academia, industry, and regulatory agencies) • Recommend nominees for vacancies in elected positions to the President
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MEMBERSHIP AFFAIRS COMMITTEE Name Region Country Natalie Hosea, Chair North America United States Christine Beedham Europe United Kingdom Ziqiang Cheng Asia Pacific China Nina Isoherranen North America United States David Stresser North America United States Ping Zhao
North America
United States
Primary Duties: • Advise Council on initiatives for improving the relationship between the Society and its members • Advise Council on initiatives to enhance member services and benefits, and on strategies to increase Society membership • Implement initiatives intended to increase the involvement of new investigators in ISSX activities • Review requests for membership grants and recommend potential recipients to Council Continued on next page
SCIENTIFIC AFFAIRS COMMITTEE Name Region Country R. Scott Obach, Chair North America United States Tom Baillie North America United States Eric Chan Asia Pacific Singapore Marcel Hop North America United States Barry Jones Europe United Kingdom Ross McKinnon Asia Pacific Australia Mario Monshouwer North America United States Yoichi Osawa North America United States Ikumi Tamai Asia Pacific Japan Ylva Terelius
Europe
Sweden
C. Roland Wolf
Europe
United Kingdom
Yasushi Yamazoe
Asia Pacific
Japan
Mike Zientek
North America
United States
Primary Duties: • Work with Council and staff to initiate and plan meetings of the Society • Develop, along with Council and ISSX staff, a specific plan and calendar for the next five years' of regional and international meetings • Review the scientific content of Society meetings and provide feedback to MOCs and Council • Engage the Council effectively in strategic initiatives such as partnership with other meetings (e.g. MDO, JSSX, and CSSX)
CONTINUING EDUCATION COMMITTEE New this year is the Continuing Education Committee. Its initial commission is to recommend, develop, and execute a series of online learning activities of appropriate scientific nature in the form of webinars to increase awareness of ISSX, especially to nonmembers, provide additional member benefits and value to members, and deliver education between regular ISSX scientific meetings. Inaugural members of this committee are:
Elizabeth Gillam
Asia Pacific
Australia
We tremendously value the support and service of our committee members. If you are interested in serving the Society as part of a task force or as a committee or Council member, we want to hear from you! Express your interest by visiting issx.org/volunteer.
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Andrew Parkinson North America United States Natalie Hosea North America United States
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Name Region Country Jasminder Sahi, Chair Asia Pacific China Cyrus Khojasteh North America United States Steve Wrighton North America United States Margaret James North America United States Barry Jones Europe United Kingdom Michael Sinz North America United States
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 issx.org/advertising or contact Steve Rabeor at srabeor@issx.org.
Change of Address
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 website. If you have forgotten your username and/or password, please contact information@issx.org.
Deadline for the submission of material to the ISSX Office: ISSUE
MATERIALS DEADLINE*
RELEASE DATE
Issue 3, 2016
September 1, 2016
October 2016
Issue 4, 2016
November 1, 2016
December 2016
*
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, it is also available to anyone who visits the ISSX website. Visit issx.org/advertising or contact Steve Rabeor at srabeor@issx.org.
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