Volume 40 Issue 4, 2017 ISSX President’s Message

By Geoff Tucker, ISSX President

The North American Meeting in or European regions were successful Finally, the time Providence, Rhode Island at the in the last round of elections. This for me to step end of September attracted 630 may reflect the current make-up of down as attendees, and Meeting Chairs ISSX membership, being 61% from President is Jash Unadkat and Alan Rettie are to North America and 19% from both approaching be congratulated on their excellent Asia Pacific and Europe, and is rapidly. In organization of a well-balanced clearly not sustainable for an Providence I program. For me, a highlight of international society. Accordingly, already passed the meeting was the outstanding Council agreed that the by-laws the chain of Geoff Tucker, Ph.D. presentations by the recipients should be modified to rectify the office (a rather ISSX President. of the North American Scientific situation. How exactly to assure attractive Achievement Awards, Kathy global representation is under accessory engraved with the names Giacomini and Namandje Bumpus. discussion and, in due course, of all previous Presidents that Steve members will be asked to ratify a Kemp keeps under lock and key) A face-to-face meeting of Council proposed change to the statutes. to my successor, Tom Baillie. in Providence allowed time for a Serving ISSX in the role of President reflective and productive discussion Meanwhile, programming plans for over the last two years has been on strategic issues, with focus the upcoming 2018 meetings in an interesting and enjoyable particularly on membership benefits, Montreal and China are proceeding experience. For that I have to thank conference programing, and Council apace, and further webinars are my fellow Council members for their structure and function. Expect to planned. The most recent webinar continued support and, of course, see outcomes in terms of action was presented on October 26 by Phil Steve and the management team over the next year. A specific Smith and was titled ‘Quantitative for their awesome efficiency, without issue that was discussed was targeted absolute proteomics which the job would have been the disappointing fact that no (QTAP): Methods and applications infinitely harder. My best wishes nominations for new Council for studies of proteins that modulate to Tom as the incoming captain in members from the Asia Pacific xenobiotic disposition.’ steering ISSX to new horizons.

IN THIS ISSUE

2 Book Review 6 22nd North American ISSX Meeting 12 Save the Date for Future Meetings 3 6th Asia Pacific ISSX Meeting 11 ISSX Welcomes New Members Book Review

NATURAL PRODUCTS TARGETING Toxicological Implications,’ ‘Targeting Enzymatic CLINICALLY RELEVANT Pathways with Marine-Derived Clinical Agents,’ ‘Anti- Editors: P.B. Andrade, P. Valentao, D.M. Pereira. Malarial Drug Discovery: New Inhibitors,’ John Wiley and Sons Inc. ‘Natural Plant-Derived Acetylcholinesterase 352pp., ISBN-13: 978-3-527-34205-1 Inhibitors: Relevance for Alzheimer’s Disease.’

Natural products have been exploited by mankind for As well as containing a wealth of information, each aeons as potential medicinal aids, albeit typically as chapter has its own reference section citing more crude mixtures. Recently such bioactive molecules detailed texts and original observations and a lengthy have been isolated, purified and examined for index allows easy searching and cross referencing. their usage within the field of therapeutics. Usually As usual, these books are well-made and pleasing results are confusing with many molecules having a to read. Recommended for those whose interests ‘significant effect’ but the underlying reasoning has lie within field or are slanting towards the area been evasive. This book collects together and presents of natural product medicines. The wide coverage information on enzyme systems that are known to be also provides a useful ‘entry’ into the topic. targeted by natural products and seeks to integrate and understand probable mechanisms of action. As Reviewed by explained in the promotion, ‘this volume serves as Steve Mitchell a companion for the medicinal chemist looking for Faculty of Medicine innovative small molecule compounds as well as for Imperial College London pharmacologist interested in the clinical effects and London SW7 2AZ, UK mode of action of herbal and traditional medicines.’ Book Ordering Information: Some 50 or so authors have collectively presented the John Wiley and Sons text as twelve chapters that are copiously subdivided Corporate Headquarters into many sections. The major chapter headings are; 111 River Street ‘Natural products as enzyme inhibitors,’ ‘Molecular Hoboken, NJ 07030-5774 Targets of Clinically Relevant Natural Products United States of America from Filamentous Marine Cyanobacteria,’ ‘Natural Telephone: 201.748.6000 Angiotensin Converting Enzyme (ACE) Inhibitors with Facsimile: 201.748.6088 Antihypertensive Properties,’ ‘Phospholipase A2 Email: [email protected] Inhibitors of Marine Origin,’ ‘β-Secretase (BACE1) Inhibitors from Natural Products,’ ‘Hypoglycaemic The Atrium Effects of Plants Food Constituents via Inhibition Southern Gate, Chichester of Carbohydrate-Hydrolysing Enzymes: From West Sussex PO19 8SQ Chemistry to Future Applications,’ ‘Natural Products England Targeting Clinically Relevant Enzymes of Eicosanoid Telephone: 44.1243.779777 Biosynthesis Implicated in Inflammation and Cancer,’ Facsimile: 44.1243.775878 ‘Anti-HIV Natural Products,’ ‘Natural Inhibitors of Mitochondrial Respiratory Chain: Therapeutic and Issue 4, 2017 / ISSX Newsletter / 2 6th Asia Pacific ISSX Meeting Zhejiang University • Hangzhou, China • May 11–14, 2018

Make plans to attend the 6th Asia Pacific ISSX Meeting Industry-Sponsored Sessions in exciting Hangzhou—the capital of China’s Zhejiang province. Zhejiang University is the home of the 6th Asia Parallel Sessions: Pacific ISSX Meeting. Sometimes referred to as Zheda, Zhejiang University was founded in 1897. It is one of In Vivo Function and Regulation of Drug Transporters China's oldest, most selective, and most prestigious Chairs: Yuichi Sugiyama and Wooin Lee, and Hua Li institutions of higher education. Called a splendid city by visitor Marco Polo, you will agree that Hangzhou Use of “Extended Clearance Concept” to Predict is a beautiful part of China not to be missed. Clinical Outcomes from In Vitro and Transport Data; Focusing on the Transporters Submit an abstract today at www.issx.org/apabstract. in the Liver Abstract submission deadline is February 28, 2018. Yuichi Sugiyama, RIKEN Institute

Scientific Program The Use and Abuse of Extended Clearance Concept (Preliminary and subject to change) Ayman El-Kattan, Pfizer, USA

Friday, May 11, 2018 Time-dependent and Long-lasting Inhibition of OATP Transporters Short Courses/Workshops: Yoshihisa Shitara, Sanofi

Integrated DMPK IND Enabling Studies Complexity and Diversity in SLCO Transporters, via Epigenetic and Splicing Regulation Mechanistic PK/PD Modeling and Simulation: Wooin Lee, Seoul National University Steps to Become a PBPK/QSP Modeler Chair: Yanyan Zhang Role of P-glycoprotein in BBB Penetration and Respiratory Toxicity of Opioid Drugs Application of PBPK Modeling in Drug Discovery Hua Li, Academy of Military Medical Sciences and Development: Case Studies Chair: Houfu Liu ADMET of Drugs and Chemicals Chairs: Bill Smith, Sylvia Zhao, and Genfu Chen Career Development Implications of Human P450 Structures Career Development Session for Drug Design James Halpert, University of Connecticut Saturday, May 12, 2018

Utility of Transgenic Mice for Identification Issue 4, 2017 of Biomarkers and Metabolism-Mediated Opening Ceremony Toxicological Mechanisms Xinxin Ding, University of Albany Keynote Lectures: From Enzymology to Human ADME: Case study

• Targeted Covalent Drugs and the Promise / of a Disproportionate Metabolite of Personalized Medicine ISSX Newsletter Bill Smith, Gilead Sciences, Inc. Tom Baillie, University of Washington Unraveling the Contribution of Aldehyde Oxidase • Cellular Pharmacokinetics to Drug Clearance: Getting Closer to an Elusive Guangji Wang, China Pharmaceutical University Parameter Mike Zientek, Takeda Poster Sessions / 3 Continued on next page 6th Asia Pacific ISSX Meeting Continued from previous page

MicroRNAs in the Regulation of DMPK Poster Sessions Yu Am, University of California, Davis Drug Interactions and Regulatory Guidance Panel Discussion and Q&A Chairs: Dafang Zhong and Chuang Lu

Poster Session Comparative Evaluation of Coproporphyrins I and III with other Endogenous Compounds as Markers of Welcome Reception OATP Inhibition in Healthy Subjects Hong Shen, Bristol-Myers Squibb Sunday, May 13, 2018 Clinical Trials Using Radiolabeled Drugs Keynote Lecture: Dafang Zhong, Chinese Academy of Sciences

• Role of Transporters in Pharmacokinetics (PK)/ How PBPK Modeling Can be Leveraged for Drug-drug Pharmacodynamics (PD )/Toxicodynamics (TD) Interactions Professor Yuichi Sugiyama, RIKEN Institute Lu Chuang, Sanofi

Parallel Symposia: ADMET of Herbal Medicine Chairs: Ge Lin and Chuan Li Personalized Medicine—Roles of Omics and Disease States CYP-mediated Metabolic Activation and Pyrrole- Chairs: John Miners & Min Huang Protein Adduct Formation—The Cause and Biomarker of Pyrrolizidine Alkaloid N-Oxide Induced Predictive Pharmacogenomic Biomarkers Herbal Hepatotoxicity for Personalized Medicine Tomorrow Ge Lin, Shanghai Institute of Materia Medica Magnus Ingelman-Sundberg, Karolinska Instuitute Metabolism-mediated Toxicities of Terpene Pharmacogenomic of Drug-induced SCARs Furanoids Wichittra Tassaneeyakul, Khon Kaen University Jian Zheng

Omics-based Personalized Medicine Role of the Herbal Medicine in Drug Interactions: Min Huang, Sun Yat Sen University Perpetrator and Victim Chuan Li, Chinese Academy of Sciences The Role of the Kidney in Drug Metabolic Clearance: Renal and the Effects of Impaired Awards for Best Abstracts and Young Speakers Renal Function on Non-Renal Drug Metabolic Clearance Banquet John O. Miners, Flinders University Monday, May 14, 2018—Sunrise Forum Drug Interactions and Liver Injury Session Chairs: Mike Sinz & Eric Chan Hot Topics in Drug Metabolism Drug-Drug Interactions: Enzyme Induction Mike Sinz, Bristol-Myers Squibb Development of Natural Products via Uncommon CYP Reactions PBPK-modeling of Complex DDIs between Li Sy, Quindao Institute of Bioenergy and Bioprocess Rivaroxaban and Amiodarone Technology, Chinese Academy of Sciences Eric Chan, National University of Singapore

Issue 3, 2017 Role of Gut Microbiota in Drug Metabolism / Disease Effect on Liver Drug Metabolism Yan Ru, University of Macau Wen Xie, University of Pittsburgh Epigenetic Activation of the Drug Transporters Disruption of Mitochondria Glucose Oxidation in Cancer Cell Pathway Sensitizes Liver to Acute Injury Prof. Yu, Zhejiang University Li Wang, University of Connecticut ISSX Newsletter

/ Industry-Sponsored Sessions Continued on next page 4 6th Asia Pacific ISSX Meeting Continued from previous page

Emerging Field of DMPK Mediated Efficacy and Toxicity Interaction Potential of New Chemical Entities Sandhya Mandlekar, Bristol-Myers Squibb Drug Interaction of Metformin and Scutellariae Radix in Mice Development and Application of Specific Probes Young Hee Choi, Dongguk University and Biosensors of Metabolizing Enzymes G. Ge, Shanghai University of Chinese Medicine Application of PBPK in Patient Treatment with Co-administered Drugs DMPK in Drug Discovery and Development XQ Xiang, Fudan University Disposition of Cell Therapeutics Regulation of Metabolizing Enzymes and HF Song, Beijing National Proteomics Research Transporters via P53 and its Effect on Liver Injury Center Bihui Zhong, Sun Yat Sen University Direct Quantification of Drugs in Organelles Application of Advanced Drug Metabolism Models from Living Cell by Mass Spectrometry Kenji Yahata, Sanofi Characterization and Application of Novel P450 Knockout Rat Models New DMPK Approach to Botanical Drug Development X. Wang, East China Normal University Mingshe Zhu, MassDefect Technologies

Animal Models in the Prediction of Drug-Drug Closing Ceremony

Meeting Organizing Committee Chairs: Su Zeng, Zhejiang University Jasminder Sahi, Sanofi, China Committee Members: Scientific Advisory Board: Eric Chan, National University of Singapore, Singapore Thomas Baillie, United States Haiping Hao, China Pharmaceutical University, Nanjing Uwe Fuhr, Germany Hiroyuki Kusuhara, University of Tokyo, Japan Frank Gonzalez, United States Zuohan Hu, Research Institute for Liver Disease, Shanghai James Halpert, United States Min Huang, Sun Yat-sen University, Guangzhou Natalie Hosea, United States Huidi Jiang, Zhejiang University, Hangzhou William Griffith Humphreys, United States John O. Miners, Flinders University, Australia Urs A. Meyer, Switzerland Hua Li, Institute of and Toxicology, Beijing Sonia de Morais, United States Ge Lin, Hong Kong Chinese University, Hong Kong Scott Obach, United States Houfu Liu, GlaxoSmithKline, Shanghai Bill J. Smith, United States Michael Sinz, Bristol-Myers Squibb, India Yuichi Sugiyama, Japan Wichittra Tassaneeyakul, Khon Kaen University, Thailand Geoff Tucker, United Kingdom Young Jin Chun, Chungang University, South Korea Nicolas P.E. Vermeulen, the Netherlands Lushan Yu, Zhejiang University, Hangzhou Hiroshi Yamazaki, Japan Issue 4, 2017 Zahurin Mohamed, University of Malaya, Malaysia Su Zeng, China Jiang Zheng, Shenyang Pharmaceutical University, Shenyang Mike Zientek, United States Dafang Zhong, Shanghai Institute of Materia Medica, Shanghai Mingshe Zhu, MassDefect Technologies, United States / ISSX Newsletter Hangzhou has direct and frequent flights with major Submit an abstract today at www.issx.org/apabstract. cities in China and also some international destinations, including Paris, Tokyo, Seoul, Singapore, and Bangkok. Information regarding meeting registration will It is within the fast transport network of east China, be posted soon. and enjoys convenient high-speed rail and highway

connection with popular tourist cities in this area, like / Shanghai, Suzhou and Nanjing. 5 22nd North American ISSX Meeting Palais des congrès de Montréal • July 15–19, 2018

Make plans to join us at the must attend event of • A vail yourself of the many opportunities for 2018—the 22nd North American ISSX Meeting. With a substantive conversation and networking with broad range of highly relevant short courses, symposia, scientists worldwide and poster presentations; new investigator and ISSX Focus Group sessions, social events, save the dates • Lear n more about and participate in one or of July 15–19, 2018 for an exciting scientific program more of our Focus Group sessions in one of Canada’s best meeting venues. • Meet with our exhibitors who will showcase This meeting will bring together individuals who are the products and services that could be helpful actively working on drug/ xenobiotic research in diverse solutions for you in your research and development fields including basic and clinical pharmacology and therapeutics, toxicology, oncology, endocrinology, • Engage with other new investigators in a special physiology, biochemistry, medicinal chemistry, molecular session designed just for you and structural biology, and genetics. If you work in the fields of toxicology, pharmacology, or molecular biology • Compete for prizes in the student and postdoc or if you study xenobiotics, you will want to attend the poster competition 22nd North American ISSX Meeting where you can: • Enjoy informal social interactions with fellow • Par ticipate in your choice of multiple short courses researchers, and also enjoy exploring Montreal designed to deliver a broad-based educational and its historical sites, trendy shops, modern experience galleries, and exceptional restaurants.

• Attend outstanding lectures delivered by leading A striking union of European charm and North American scientists who will share the latest developments attitude, Montréal provides visitors with a harmonious in their areas of research pairing of the historic and the new, from exquisite architecture to fine dining. We’ll have great science, • Gain recognition and feedback on your research time to meet with vendors offering the latest products by submitting an abstract and presenting a poster and services important to aid in your research, and plenty of opportunity for making new acquaintances and rekindling friendships in the heart of beautiful Montréal!

Meeting Organizing Committee

Jack Uetrecht, Chairman Ahmed Almousa Tom Massey University of Toronto University of Saskatchewan Queen’s University

Tom Baillie Rachel Tyndale Rommel Tirona University of Washington University of Toronto University of Toronto

Issue 4, 2017 Scott Obach Chantalle Guillemette Leanne Bedard

/ Pfizer Inc. Laval University Bedard ADME-Tox Solutions

Sonia de Morais Shinya Ito William (Griff) Humphreys Hospital for Sick Children Bristol-Myers Squibb ISSX Newsletter /

6 Continued on next page 22nd North American ISSX Meeting Continued from previous page

Scientific Program 11:00–11:35 Data Fitting/Interpretation (Subject to Change. Speakers to be Invited.) Jane Kenny, Genentech

Sunday, July 15, 2018 11:35–12:15 PBPK Modeling Ping Zhao, Bill & Melinda 09:00–12:15 | Short Courses 1 and 2 Gates Foundation

Short Course 1: Model Systems and Methods for 13:30–16:45 | Short Courses 3 and 4 Assessing Uptake and Efflux of Small Molecules Co-chairs: Yurong Lai, Gilead Sciences, and Short Course 3: Modeling: Incorporating Quantitative Sonia de Morais Proteomic Data from both Drug Metabolizing Enzyme and Transporter Tissue Expression into Models to 09:00–09:45 Novel in vitro Models Improve Prediction of DDI, Drug-disease Interaction, to Study Transporters Relevance of Pharmacogenetics and Drug Response Yurong Lai, Gilead Chair: Iain Gardner, Certara

09:45–10:30 Animal Models for Drug Transporters 13:30–13:50 Why is Modeling of in vitro Data (Genetically Modified Mice, Monkeys, Important? etc.) Iain Gardner, Certara Dan Bow, AbbVie 13:50–14:10 Experimental Approaches to 10:30–10:45 Refreshment Break Understand Intracellular Based Drug Bioavailability 10:45–11:30 PET imaging to Understand Per Artursson, Uppsala Hepatobiliary Transporters Yuichi Sugiyama, RIKEN 14:10–14:30 In silico Approaches to Modeling Transporter Data 11:30–12:15 Pr obe Drugs for Transporter Manthena Varma, Pfizer Phenotyping Mitch Taub, Boehringer Ingelheim 14:30–14:50 Mechanistic Modeling of in vitro Assays to Improve in vitro/in vivo Short Course 2: Enzyme Induction and Regulatory Extrapolation Guidance Viera Lukacova, Simulations Plus Co-chairs: Niresh Hariparsad, Vertex Pharmaceuticals, and Eva Gil Berglund, European Medicines Agency 14:50–15:05 Refreshment Break

09:00–09:35 Intr oduction to the Fundamentals 15:05–15:25 Simultaneous Modeling of of Induction Metabolism, Competitive and Michael Sinz, BMS Mechanism Based Inhibition Howard Burt, Certara Issue 4, 2017 09:35–10:10 Gene Regulation (Transcription Factor, Non-nuclear Receptor and 15:25–15:55 Hands on Exercise Modeling in vitro miRNA) Metabolism Data Masahiko Negishi, National Institute of Environmental Health Sciences 15:55–16:45 V irtual Cell Models to Predict Binding

and Distribution of Chemicals in in / 10:10–10:45 T echnical Aspects Related to in vitro vitro Toxicity Assays ISSX Newsletter Induction Assessment Ciaran Fisher, Certara Steve Ferguson, National Institute of Environmental Health Sciences

10:45–11:00 Refreshment Break / 7 Continued on next page 22nd North American ISSX Meeting Continued from previous page

Short Course 4: Immunotoxicology 14:00–16:00 | Parallel Symposia 1 and 2 Chair: Jinze (Robert) Li, Genentech Symposium 1: Transporters as Determinants of Target 13:30–14:10 Developmental Immunotoxicology Organ Toxicities and Regulation of Drug Transporters Mark Collinge, Pfizer and Metabolizing Enzymes by Nuclear Receptors: Implications in Clinical Drug Disposition and 14:10–14:50 On-tar get related Immunotoxicity Therapeutics Lee Dong, Genentech Chair: Rommel Tirona, University of Toronto

14:50–15:05 Refreshment Break 14:00–14:30 Kidney Transporters and Nephrotoxicity 15:05–15:45 Immunological Components Rosalinde Masereeuw, Utrecht of Liver Injury University Cynthia Ju, McGovern Medical School 14:30–15:00 T ransporters and DILI 15:45–16:15 Nonclinical Immunotoxicity Testing Kim Brouwer, UNC Assessment Jennifer Wheeler, BMS 15:00–15:30 T ransporters and Heavy Metal Toxicity Elaine Leslie, University of Alberta 17:00–18:00 | New Investigators Meet Up 15:30–16:00 Unconventional ABC Efflux 18:00–18:15 | Opening and Welcome Remarks Transporters and Drug Toxicity ISSX President, Tom Baillie, University of Washington, John Schuetz, St. Jude Children’s and Meeting Chair Jack Uetrecht, University of Toronto Research Hospital

18:15–19:00 | Opening Keynote Lecture Symposium 2: Development of Guidelines to Implement Pharmacogenomics-based Clinical Decision 19:00–21:00 | Opening Welcome Reception Chair: Rachel Tyndale, University of Toronto in Exhibit Hall 14:00–14:30 Phar macogenomics in Drug Response Monday, July 16, 2018 and Safety Assessment Ann Daly, Newcastle University 08:30 - 09:30 | Parallel ISSX Focus Group Sessions 14:30–15:00 Academic and Industry Perspectives FG 1: Biotransformation Mechanisms & Pathways on Pharmacogenomics: Drug Co-chairs: Amit S. Kalgutkar, Pfizer, and Barry Jones, Optimization AstraZeneca Alan Shuldiner, University of Maryland School of Medicine and Geisinger FG 2: Modeling & Simulations Co-chairs: Hartmut Derendorf, University of Florida, 15:00–15:30 Using Electronic Medical Records to and Yusuke Tanigawara, Keio University Advance Genomic Medicine - Novel Approaches for Finding Actionable 09:45–10:30 | Plenary Lecture 1 Pharmacogenomics Novel Approaches for Measurement of Intracellular Joshua Denny, Vanderbilt Drug Concentrations: Utility in Clinical Translation Dennis Smith, University of Capetown 15:30–16:00 Bioinfor matics: Accumulating and Implementing Pharmacogenomics Issue 4, 2017

/ 11:00–12:30 | Society Awards Presentations Information and Lectures Teri Klein, PharmGKB/Stanford

12:30–14:00 | Lunch on Own, Visit with Exhibitors, 16:30–18:30 | Oral Presentation of Selected Abstracts Posters Attended by Authors from New Investigators ISSX Newsletter /

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18:30–20:00 | New Investigators Session 12:00–13:30 | Lunch Break, Visit with Exhibitors, and Reception Posters Attended by Authors

Tuesday, July 17, 2018 13:30–14:30 | Debate

07:30– 08:30 | Parallel Industry Symposia 14:30–18:00 | Free Afternoon to Explore Montréal

08:45–09:30 | Plenary Lecture 2 Wednesday, July 18, 2018

Novel Synthetic and Computational Approaches 07:30–08:30 | Parallel Industry Symposia to the Discovery of Drugs Targeting Nonalcoholic Fatty Liver Disease 08:45–09:30 | Plenary Lecture 3 Wes Westlin, Nimbus Therapeutics Site-specific Deuterium Labeling: A Viable Approach 10:00–12:00 | Parallel Symposia 3 and 4 in Drug Discovery and Development Margaret Bradbury, Teva Pharmaceuticals Symposium 3: The Impact of Pregnancy on Xenobiotic Disposition 10:00–12:00 | Parallel Symposia 5 and 6 Chair: Shinya Ito, Hospital for Sick Children Symposium 5: Revisiting the Regulatory Guidelines 10:30–11:00 Dysr egulation of Transporters in (FDA, EMA) for Drug Interaction Studies and Maternal Disease; Potential Impact Regulatory DMPK on Fetal Drug Exposure Chair: Niresh Hariparsad, Vertex or Donald Tweedie, Micheline Piquette-Miller, University Merck of Toronto 10:00–10:30 In vitro to in vivo Extrapolation 11:00–11:30 Pr edicting and Verifying Maternal- Ken Grime, AstraZeneca Fetal Exposure to Drugs During Pregnancy 10:30–11:00 Regulator y Requirements to Assess Jashvant Unadkat, University Induction of Washington Eva Gil Berglund, European Medicines Agency Symposium 4: Genomic Approaches for Revealing Mechanisms of Cancer Drug Efficacy and Toxicity 11:00–11:30 Considerations from the IQ Induction Co-chairs: Chantal Guillemette, Université Working Group in Response to Drug- Laval, and Tom Massey, Queen’s University Drug Interaction Guidances from Regulatory Agencies 10:00–10:30 Genetic Predictors and Underlying Niresh Hariparsad, Vertex Mechanism of Treatment-Related Complications in Childhood Acute 11:30–12:00 Futur e Perspectives Related Lymphoblastic Leukemia to Induction Maja Krajinovic, University of Montreal Ed LeCluyse, LifeNet Health Issue 4, 2017

10:30–11:00 Genome-guided Medications Symposium 6: Microphysiological Systems/Organs for Safer and More Effective on a Chip Treatment of Disease Co-chairs: Jinping Gan, BMS, and Sonia de Morais

Colin Ross, University of /

British Columbia​ 10:00–10:30 A Human Liver Microphysiology ISSX Newsletter System for Drug Discovery and 11:00–11:30 Newest Approaches to Safety Development Assessment in Drug Development Lansing Taylor, University of Pittsburgh Jeffrey Willy, Lilly

11:30–12:00 Selected Abstract Presentations / 9 Continued on next page 22nd North American ISSX Meeting Continued from previous page

10:30–11:00 Linked Organs-on-Chips for Probing Symposium 8: Endogenous Biomarkers for Drug Xenobiotic Bioactivation, Transport Metabolism and Transporter Activity. Predicting Drug and Toxicity Interactions in Clinical Development and for Ed Kelly, University of Washington Application in Precision Medicine Chair: Griff Humphreys, BMS 11:00–11:30 The Utility of Liver Spheroids in Addressing Current Issues in Drug 16:00–16:30 Development of Endogenous Metabolism and Liver Toxicity Biomarkers for CYP3A to be Used Evaluations in Drug Interaction Studies Jinping Gan, BMS Tommy B. Andersson, Astra Zeneca

11:30–12:00 Micr ophysiological Systems in 16:30–17:00 Lectur e Title Pending Pharma: Evolving a Paradigm Kathy Giacomini, UCSF Brian Berridge, GSK 17:00–17:30 Lectur e Title Pending 12:00–13:30 | Lunch on Own, Visit with Exhibitors, Hiroyuki Kusuhara, University of Tokyo Posters Attended by Authors 17:30–18:00 Lectur e Title Pending 13:30–15:30 | Plenary Session Hong Shen, BMS

The Role of the Microbiome in Drug Metabolism Thursday, July 19, 2018 and How this Influences Drug Toxicity Chair: Tom Baillie, University of Washington 07:30–08:30 | Parallel Industry Symposia Peter Turnbaugh, UCSF 16:00–18:00 | Parallel Symposia 7 and 8 08:45–09:30 | Plenary Lecture 4

Symposium 7: Antibody Drug Conjugates (ADCs) Opportunities and Challenges in the Discovery Disposition and Modeling of Novel Agents for the Treatment of Malaria Chair: Ilaria Badagnani, Theravance Biopharma US, Inc. Jeremy Burrows, Medicines for Malaria Venture

16:00–16:30 Systems Pharmacokinetic Modeling 09:30–10:00 | Presentation of the ISSX Poster Awards of ADCs Presentation of 1st - 3rd Place Poster Awards for Dhaval Shah, SUNY Buffalo Predoctoral/Graduate Posters and for Postdoctoral Posters 16:30–17:00 Intra-tissue Catabolite Characterization is a Missing Link 10:15–12:15 | Parallel Symposia 9 and 10 in Discovery of ADCs Donglu Zhang, Genentech Symposium 9: Analytical Technology Session Based Around New Methods for Bioanalysis Metabolite 17:00–17:30 In vitro and in vivo Mechanisms Identification, etc. of ADCs Disposition and Activity Co-chairs: Mingshe Zhu, BMS, and Kevin Bateman, Merck Colin Philips, AbbVie 10:15–10:45 Peptides as Drugs - Challenges 17:30–18:00 Characterization and ADME Properties in Bioanalysis, Metabolism, of a Novel Auristatin Payload-based Permeability, etc. ADC Mark Cancilla, Merck Issue 4, 2017 Mauricio Leal, Pfizer / 10:45–11:15 Dr ug Target Quantitation, Translational PK/PD Hendrik Neubert, Pfizer

11:15–11:45 Biotransfor mation of ADCs Donglu Zhang, Genentech ISSX Newsletter /

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Symposium 10: Designed Covalent Inhibitors, ADME 12:15–12:30 | Closing Session Aspects of Design, Characterization and Risk Assessment Submit an Abstract Chair: Tom Baillie, University of Washington Poster presentations are an integral component of ISSX meetings. We encourage all those involved in 10:15–10:45 T argeted Covalent Inhibitors the fields of metabolism, pharmacology, toxicology, for Drug Design molecular biology and other related disciplines Tom Baillie, University of Washington to consider submitting an abstract for a poster presentation at the 22nd North American ISSX Meeting. 10:45–11:15 Activity-based Proteomics—Protein We have some slots for poster authors to present and Ligand Discovery on a Global from the podium too. The abstract submission site Scale opens soon! Visit www.issx2018.com for details. Ben Cravatt, Scripps Hotel Lodging 11:15–11:45 How to be Selectively Promiscuous ISSX has reserved a block of rooms at four hotels, each Jack Taunton, UCSF within walking distance to the convention center. Review the lodging options and make your reservation via the 11:45–12:15 Covalent Binding—From 20th Century meeting web site: www.issx2018.com. Liability to 21st Century Targeted Therapies Greg Slatter, Acerta Pharma

ISSX Welcomes New Members

The International Society for the Study of Xenobiotics proudly welcomes the following new members. We greatly appreciate their support and hope that each remains aligned and affiliated with ISSX for many years to come.

Benjamin Barlock Licong Jiang, Vertex Adrian Sheldon, Charles River Labs

Yashpal Singh Chhonker, UNMC Amin Kamel, Takeda Edwin Squirewell, University of Florida Taylor Choi, Achaogen Rui Li, Pfizer Inc.

Archie Thurston, ADME Issue 4, 2017 Kevin Colizza, University Bo Liu, Novarits Solutions, Inc. of Rhode Island Enrique Martinez, Oxford Leon van Haandel, Childrens Shanal De Silva, University Biomedical Research, Inc. Mercy Hospital of Saskatchewan

Jane McGuffog, Proximagen Pengcheng Wang, / Sara Eyal, The Hebrew University of Pittsburgh ISSX Newsletter University of Jerusalem Chandrasekhar Natarajan, Tufts School of Medicine Jeff Weber, Q2 Solutions Ryan Hitzman Natalie Nguyen, Takeda Sucha Zhang, Enanta Md Amin Hossain, Tufts University California Inc. Pharmaceuticals, Inc.

Karen Houseknecht, / 11 University of New England Save the Dates for Future ISSX Meetings

The scientific meetings organized by ISSX provide most current evidence. The chance to view the latest exceptional opportunities for members of the scientific product lines and learn about the services of the community to exchange ideas and expertise, to companies participating in the trade exhibitions develop a common vision, and to create and nurture drive even more value to your investment. Moreover, collaborations in fields related to the study of chemicals the people that you will meet at our meetings are that are foreign to the human body. extraordinary. They are contributing to the expanding base of knowledge crucial to broadening the We offer the chance to present your research via understanding of the effects of drugs, the mechanism multiple formats at our meetings that we hold in North of their actions, and the movement of drugs throughout America, Asia, and in Europe. organisms.

Short courses at our meetings on a variety of important Please be sure to include funds in your training budget topics are a popular way to gain invaluable training. for you as well as your scientific team and participate Scientific symposia tracks offer a multitude of options in our very high quality meetings that are organized by and forums for attendees to learn the most recent teams of leading educators and investigators worldwide: developments incorporating the newest ideas and the

6th Asia Pacific ISSX Meeting 22nd North American ISSX Meeting Zhejiang University Palais des congrès de Montréal Hangzhou, China Montreal, QC Canada May 11–14, 2018 July 15–19, 2018 Meeting Chairs: Su Zeng, Ph.D., Meeting Chair: Jack Uetrecht, M.D., Ph.D. Jasminder Sahi, PhD., and Zhuohan Hu, Ph.D.

12th International ISSX Meeting ISSX Joint Scientific Meeting with 23rd ISSX North American Portland Convention Center The European Association for and 35th JSSX Meeting Portland, Oregon, USA Clinical Pharmacology and Hilton Waikoloa Village July 29–August 1, 2019 Therapeutics Waikoloa, Hawaii, USA Meeting Chairs: Aleksandra Galetin, Centre International de October 4–8, 2020 Ph.D., Hiroyuki Kusuhara, Ph.D., and Conférences Genève Meeting Chairs: Allen Rettie, Ph.D. Deepak Dalvi, Ph.D. June 7–11, 2020 and Hiroshi Yamazaki, Ph.D. Meeting Chairs: Jules Desmeultes, Ph.D. and Caroline Samer, Ph.D.

ISSX seeks proposals from members who may wish via ISSX Headquarters at least 4-5 years in advance to organize scientific meetings. Individuals who wish of the contemplated date of the meeting. For more to organize an ISSX meeting are welcome to submit a information, go to www.issx.org/submit.

Issue 4, 2017 proposal and contact the Scientific Affairs Committee / ISSX Newsletter / 12 ISSXS Full Page Ad 8.5 by 11_Final for Print.pdf 1 11/10/2017 4:48:15 PM

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High quality, TRANSPORTER Comprehensive in vitro liver ACCULIVER™ kits, when combined with TRANSPORTER CERTIFIED CERTIFIEDTM and LIVERPOOLTM programs to assess ADME-Tox and efficacy. hepatocytes, have demonstrated hepatocytes to ensure consistent in better in vitro - in vivo correlation vivo relevant data for your research. than conventional models.

Discover how our products and services can accelerate your research by visiting www.bioivt.com.

LIVERPOOL® and BioreclamationIVT are registered trademarks and trademarks of BioreclamationIVT. TRANSPORTER CERTIFIED™ and ACCULIVER are trademarks of Qualyst Transporter Solutions. Header ISSX Newsletter is published quarterly in the spring, Change of Address summer, autumn, and winter. For information If your mailing address, telephone, fax number, or e-mail concerning advertising in this publication, including has changed or will change, please let us know as soon rates and specifications, please visit issx.org/advertising as possible. You may update your contact information or contact Stephanie Young at [email protected]. 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 [email protected].

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