ASIAN ADMET SYMPOSIUM REPORT 2009
OVERVIEW
The first Asian Symposium on ADMET Profiling in Drug Discovery was successfully
held on the 15th-16th September 2009, at the NUSS Kent Ridge Guild House. The
specific emphasis of this Symposium was Metabolism and Medication Safety. The
objectives of this symposium are two-fold: to create an awareness of the relevance and
implication of ADMET to pharmaceutical sciences and drug development amongst the
burgeoning regional research communities; and secondly, bring together local and
regional scientists for potential collaborative research and exchange of ideas in this
exciting field. Additionally, this symposium also included an educational outreach effort
by including a series of talks by graduate student/post-doc from around the world through
an in-house Travel Award Program. Overall, the event was very well subscribed and the
feedback was highly encouraging. We will share some of the highlights of this event.
GOH speech
(1st and 2nd picture, left to right) A/Prof Go Mei Lin delivering the opening speech for the inaugural Asian
Symposium on ADMET Profiling in Drug Discovery; (Last picture) A/Prof Chan Sui Yung, HoD of
Department of Pharmacy, presenting a token of appreciation to A/Prof Go Mei Lin.
Department of Pharmacy, National University of Singapore
2009
ASIAN ADMET SYMPOSIUM REPORT 2009
Our guest-of-honor for the Symposium is A/Prof Go Mei Lin, Deputy Head of the
Department of Pharmacy. She gave the opening address and also presented the Travel
Awards to respective recipients. Below is an excerpt from her speech:
“Distinguished Speakers, Invited Guests, Ladies and Gentlemen, I bid you a warm
welcome to the Asian Symposium on ADMET Profiling for Drug Discovery. The Theme
of the Symposium is Metabolism and Drug Safety.
Safety and Efficacy are the twin requirements for any therapeutic agent. Unfortunately,
they do not always go hand-in-hand and herein lies the dilemma. Issues relating to safety
of the administered agent can surface at any phase of the development pipeline. In 2006,
a phase 1 trial with a monoclonal antibody TGN 1412 went horribly wrong, resulting in
all its six male volunteers taken seriously ill with multiple organ failure. About two years
earlier, there was the widely publicized drug withdrawal of the Cox-2 inhibitor rofecoxib
(Vioxx) from the US market. Lack of safety and efficacy are the two main reasons why
clinical candidates continue to fail in development. Thus, the topics discussed in this
symposium provide a timely reminder of the urgency of the matter and how we may do
better in this area.
Over the next two days, renowned experts will provide authoritative views on this topic.
There will be presentations on the central role of ADME in drug safety with specific
reference to reactive metabolites from the view point of structure-toxicity relationships,
covalent binding properties of these metabolites, and quinones- a notorious
representative of this class. You will also hear of the predictive aspects of ADMET
profiling, namely metabolomics and physiologically based PK modeling , as well as the
practical – namely PK/PD in children, microdosing in PK analysis and pharmacogenetics.
May I extend my congratulations to the organizing committee chaired by Dr Eric Chan
and Dr Ho Han Kiat of the Department of Pharmacy, for their hard work and dedicated
effort in putting together an outstanding programme. Special thanks to the sponsors for
their generous support in providing travel grants to 6 participants from India, Vietnam,
USA, Malaysia and Singapore who will be sharing their research findings in this meeting.
Finally, to all present, especially the graduate students, may you have an enriching
learning experience and a great time forging new ties and renewing old ones.”
PROGRAMME
DAY ONE: 15th September 2009, Tuesday:
9:00 – 9:30 AM
Registration
9:30 – 10:00 AM
Welcome Address and Award Presentation
Department of Pharmacy, National University of Singapore
2009
ASIAN ADMET SYMPOSIUM REPORT 2009
10:00 – 10:50 AM
Keynote Speaker: Prof Dhiren Thakker, University of
North Carolina
Title: Role of ADME in adverse effects of drugs
10:50 – 11:20 PM
TEA BREAK
11:20 – 12:10 PM
Prof Sid Nelson, University of Washington
Title: Structure toxicity relationships in reactive
metabolite-mediated drug toxicities
12:10 – 1:00 PM
Prof Salmaan H Inayat-Hussain, Universiti Kebangsaan
Malaysia
Title: Quinone toxicity- Friend or foe?
1:00 – 2:20 PM
LUNCH
2:20 – 3:10 PM
Prof James McElnay, Queen’s University Belfast
Title: PK/PD studies in children
3:10 – 4:00 PM
Dr. Peter Chan, PhD, DABT, PCTS Specialty Chemicals
Pte Ltd
Title: Risk assessment of chemicals from the perspective of
physiologically-based pharmacokinetics modeling
4:00 – 4:30 PM
TEA BREAK
4:30 – 5:00 PM
Travel award recipient: Bhagwat Prasad, NIPER, India
5:00 - 5:30 PM
Travel award recipient: Dr. Khac-Minh Thai, Univ of
Medicine and Pharmacy at Ho Chi Minh, Vietnam
5:30 – 8:45 PM
Dinner with Speakers and Award Recipients
DAY TWO: 16th September 2009, Wednesday:
8:55 – 9:00 AM
Day 2 introduction
9:00 – 9:50 AM
Dr. Hector Keun, Imperial College
Title: Metabonomics as a tool for predicting drug response
9:50 – 10:40 AM
Dr. Stephen Wise, Lilly
Title: Early clinical drug development and and utility of
pharmacogenetics
Department of Pharmacy, National University of Singapore
2009
ASIAN ADMET SYMPOSIUM REPORT 2009
10:40 – 11:10 AM
TEA-BREAK
11:10 – 12:00 PM
Dr. Ronald White, BMS
Title: Covalent binding of reactive metabolites as a
problem in industrial drug discovery
12:00 – 12:50 PM
Mr. Jason Neo, ABI
Title: Microdosing in PK analysis
12:50 – 2:00 PM
LUNCH- Meet the experts
2:00 – 2:50 PM
Dr. Vijay Suppiah, Westmead Millennium Institute
Title: Pharmacogenetics- the hepatitis C story
2:50 – 3:20 PM
Travel award recipient: William Proctor, Univ of North
Carolina, USA
Title: A Novel Mechanism for Intestinal Absorption of the
Type II Diabetes Drug Metformin: Potential Role in
Metformin Pharmacology and Adverse Effects
3:20 – 3:50 PM
TEA-BREAK
3:50 – 4:20 PM
Travel award recipient: Dr. Chan Kok Meng, Universiti
Kebangsaan Malaysia
Title: Molecular Mechanisms Of Goniothalamin-Induced
Apoptosis On Coronary Artery Smooth Muscle Cells
4:20 – 4:50 PM
Travel award recipient: Uttam Bhaumik, Jadavpur
University, India
Title: Development and validation of a LC-MS/MS method
for bioanalytical application with ranolazine
4:50 – 5:20 PM
Local award recipient: Sudipta Saha, National Univ of
Singapore
Title: Investigation of the role of the thiazolidinedione ring
and sulfo-conjugate of troglitazone in inducing
hepatotoxicity
-END-
Department of Pharmacy, National University of Singapore
2009
ASIAN ADMET SYMPOSIUM REPORT 2009
PLENARY SPEAKER
Our plenary speaker is Prof Dhiren Thakker, Associate Dean of
the School of Pharmacy at University of North Carolina. Prof
Thakker also served as the scientific advisor for our symposium.
He gave a keynote lecture that broadly address the need for
ADMET profiling in optimizing safety and efficacy of new drug
candidates in the drug development. He ended his talk strongly by
tracing the historical beginnings of drug metabolism that
confirmed its role to drug toxicity. These early principles defined
and perpetuated the advancements in the field that we are
experiencing today.
SPEAKERS
Group photo of the speakers, Department of Pharmacy staff and the award winners:
(Front row, left to right) A/Prof Chan Sui Yung, Dr. Peter Chan, Prof Salmaan Inayat-Hussain, Dr. Ronald
White, Prof Dhiren Thakker, Prof Sid Nelson and Dr. Khac-Minh Thai, Dr. Hector Keun.
(Front row, left to right) Dr Eric Chan Chun Yong, Dr. Chan Kok Meng, A/Prof Go Mei Lin, Mr Sudipta
Saha, Mr William Proctor, Mr Bhagwat Prasad, Prof James McElnay, Mr Uttam Bhaumik and Dr Ho Han
Kiat.
We have a total of 10 invited speakers for the symposium. Besides, Prof Thakker, our
overseas speakers included Prof Sid Nelson (University of Washington), Prof Salmaan
Inayat-Hussain (Universiti Kebangsaan Malaysia), Prof James McElnay (Queen’s
University Belfast), Dr. Hector Keun (Imperial College London), Dr. Ronald White
(BMS), Dr. Stephen Wise (Lilly) and Dr. Vijay Suppiah (Westmead Millennium
Department of Pharmacy, National University of Singapore
2009
ASIAN ADMET SYMPOSIUM REPORT 2009
Institute). We also had 2 local speakers namely Dr. Peter Chan (PCTS Chemicals) and
Mr Jason Neo.
Prof Sid Nelson took a more chemical approach to expound the importance of
metabolism to toxicity, identifying critical chemical features that frequently pre-dispose
to drug toxicity. Dr. Ronald White critically addressed the current approaches that
pharmaceutical industries adopt as part of their early profiling of toxicity through
identification of reactive intermediates and metabolites. Subsequently, Prof Salmaan
Inayat-Hussain examined in greater details, one particular chemical feature, the quinones,
and discussed on how the reactivity of such structure can lead to both beneficial and
adverse outcomes.
Dr. Stephen Wise, Prof James McElnay and Dr. Vijay Suppiah expounded a different
aspect of drug pharmacology and toxicology that is linked to genetics. Dr. Stephen Wise
clearly illustrated the impact of pharmacogenomics on drug toxicity and drug responses,
particularly genes those pertaining to drug metabolism. Prof McElnay discussed the
screening of genetic polymorphism in childhood leukemia, while Dr. Suppiah discussed a
separate genetic approach to look at clinical pharmacology of hepatitis C.
Finally, a few speakers addressed emerging technologies that will shape ADMET
profiling in the future. These include Dr. Hector Keun’s numerous examples on the use of
metabonomics study in drug toxicity, Dr. Peter Chan’s discussion on the use
physiologically-based pharmacokinetics modeling to improve the clinical relevance and
accuracy of pharmacokinetics profiling of drug distribution, as well as Mr Jason Neo
addressing the use of micro-dosing for large-scale pharmacokinetics profiling.
Department of Pharmacy, National University of Singapore
2009
ASIAN ADMET SYMPOSIUM REPORT 2009
TRAVEL AWARD WINNERS
A/Prof Go Mei Lin presenting the Travel Award to:
(1st row, from left to right) Mr Bhagwat Prasad, NIPER, (India), Dr. Khac-Minh Thai, University of
Medicine and Pharmacy at Ho Chi Minh (Vietnam) and Mr William Proctor, University of North Carolina
(USA).
(2nd row, from left to right) Dr. Chan Kok Meng, Universiti Kebangsaan Malaysia (Malaysia), Mr Uttam
Bhaumik, Jadavpur University (India) and Mr Sudipta Saha, National University of Singapore (Singapore).
To fulfill one of our objectives of an educational outreach to regional countries, we
instituted a Travel Award scheme whereby 5 recipients were selected based on the
scientific merits of their submitted abstracts. Abstracts were reviewed by our scientific
panel comprising of A/Prof Paul Ho and Dr. Yap Chun Wei from the Department of
Pharmacy. In the end, 5 Travel Awards ($1500 cash award each) and 1 local award
($250) were given out. These recipients presented their abstracts in the form of 25-min
talks and 5-min Q&A each, during the symposium. The winners also participated actively
in the rest of the symposium and were given ample opportunities to mingle with the guest
speakers and organizers. Some of them also participated in a half-day tour of NUS and
Biopolis the day before the symposium. The list of the winners is as shown below:
1. Mr. Bhagwat Prasad, National Institute of Pharmaceutical Education and
Research (NIPER, India)
Recipient of GSK – Dhiren Thakker Travel Award
Title: In silico and in vitro studies for identification of major CYP450 involved in
biotransformation of rifamycin derivatives
2. Dr. Khac-Minh Thai, University of Medicine and Pharmacy at Ho Chi Minh City
(Vietnam)
Recipient of Applied Biosystems – Sidney Nelson Travel Award
Title: Overcoming hERG activity in drug discovery: The systematic concept
Department of Pharmacy, National University of Singapore
2009
ASIAN ADMET SYMPOSIUM REPORT 2009
3. Mr. William Ross Proctor III, University of North Carolina (USA)
Recipient of Singapore – BMRC Travel Award
Title: A Novel Mechanism for Intestinal Absorption of the Type II Diabetes Drug
Metformin: Potential Role in Metformin Pharmacology and Adverse Effects
4. Dr. Kok Meng Chan, Universiti Kebangsaan Malaysia (Malaysia)
Recipient of Agilent Travel Award
Title: Molecular Mechanisms Of Goniothalamin-Induced Apoptosis On Coronary
Artery Smooth Muscle Cells
5. Mr. Uttam Bhaumik, Jadavpur University (India)
Recipient of Shimadzu – James McElnay Travel Award
Title: Development and validation of a LC-MS/MS method for bioanalytical
application with ranolazine
6. Mr. Sudipta Saha, National University of Singapore (Singapore)
Recipient of ADMET Local Award
Title: Investigation of the role of the thiazolidinedione ring and sulfo-conjugate of
troglitazone in inducing hepatotoxicity
PARTICIPANTS
Publicity for the event was mainly through email circulation and departmental
announcements across relevant departments in NUS, NTU, polytechnics, research
institutes and research divisions of pharmaceutical companies based in Singapore.
Approximately 160 participants registered for the event, exceeding our initial target of
120 participants. The registrants included a large number of academic scientists,
pharmaceutical scientists from the industry and research institutes, undergraduate and
postgraduate students, as well as interested individuals from relevant vendors and
licensing offices. The insightful talks presented catalyzed interactive discussions with the
audience during Q&A as well as lunches and tea breaks. Many requests for speakers’
presentation slides were communicated to the organizers.
Department of Pharmacy, National University of Singapore
2009
ASIAN ADMET SYMPOSIUM REPORT 2009
SPONSORSHIPS
Sponsorships for the event were overwhelming, allowing us to keep the event free-ofcharge so as to encourage participation (particularly helpful for undergraduate and
postgraduate students). In all, we received sponsorships amounting to $23550. The
breakdown of sponsorships by company is as shown in the table below.
Source
NUS, Faculty of Science
A*STAR BMRC Local Symposium Sponsorship
Applied Biosystems
BD Gentest
Agilent
GSK
Shimadzu
Alpha Analytical
NUSS (for allowing additional chairs without charge)
Department of Pharmacy (Miscellaneous)
Total
Amount
$10000
$5000
$2500
$2250
$1000
$1000
$1000
$800
$2268.83
$25818.83
Reported by:
Ho Han Kiat
Eric Chan Chun Yong
Department of Pharmacy, National University of Singapore
2009