TS1: INTRODUCTION TO SMALL MOLECULE DRUG METABOLISM AND APPLICATIONS TO DISCOVERY AND DEVELOPMENT
April 10-11, 2019 | SAN DIEGO CONVENTION CENTER, SAN DIEGO
WEDNESDAY, APRIL 10 | 1:30 - 5:30 PM
THURSDAY, APRIL 11 | 8:00 AM - 5:50 PM
Room Location: 31A
DAY 1: WEDNESDAY
1:30 – 5:30 pm Training Seminar in Session
3:40 – 4:30 pm Refreshment Break in Exhibit Hall
DAY 2: THURSDAY
10:45 am – 5:50 pm Training Seminar in Session
8:45 – 9:45 am Plenary Keynote Session
9:45 – 10:40 am Coffee Break in Exhibit Hall
12:30 – 1:30 pm Lunch Provided
1:30 – 2:15 pm Dessert Break in Exhibit Hall
3:50 – 4:20 pm Networking Refreshment Break
About this Training Seminar: This 1.5-day lecture-based interactive seminar, which focuses on small molecule drug metabolism, will begin with a historical background to the origin of the field before reviewing the both well recognized
and more recently discovered drug metabolism pathways. In vitro assays used to access metabolic clearance and medicinal chemistry strategies for modifying structures to overcome metabolism dependent clearance during lead-optimization will be discussed.
The topic of drug toxicity will be discussed in the context of drugs that are toxic through bioactivation to reactive metabolites, examples of drug structure-toxicity relationships and the relevance of idiosyncratic toxicity to the pharmaceutical
industry. The role of metabolite identification studies in preclinical and clinical development will be compared and the steps involved in identifying and characterizing metabolites by mass spectrometry will be explained. Advances in the use of
in silico tools in the context of drug metabolism will be explored. An overview of the pharmacological properties and functions of drug transporters and some preclinical approaches to investigate drug transport mechanisms
will be presented as well as current regulatory guidance on transporters.
Participants will see the importance of understanding drug metabolism in the different stages and processes required to advance a new chemical entity from discovery through development into the clinic, through examples and case studies. This seminar is
intended for scientists in either academia or industry who would like to become more familiar with small molecule drug metabolism.
Topics to be covered in the seminar:
- Historical background to the field of drug metabolism
- Basic drug biotransformation reactions and the enzymes responsible
- Newly recognized drug biotransformation reactions
- In vitro assays used to access metabolism-based clearance
- Medicinal chemistry strategies for overcoming poor metabolic stability
- Bioactivation pathways to reactive drug metabolites
- Role of reactive metabolites in drug toxicity, including idiosyncratic toxicity
- Role of metabolite identification studies in discovery and development
- Four steps for identifying and characterizing drug metabolites by mass spectrometry
- In silico tools to address drug metabolism and reactive metabolite formation
- Pharmacological properties and functions of drug transporters
- Preclinical approaches to investigate drug transport mechanisms
- Role of transporters in drug PK, PD, efficacy, safety, and drug-drug interactions (DDI)
- Impact of transporter studies on drug discovery and development
- Recommendations from the current regulatory guidance and International Transporter Consortium (ITC) white papers on transporter evaluation during drug development
Instructors:
John C.L. Erve, PhD, DABT, President, Jerve Scientific Consulting, Inc.
Michelle Liao, PhD, Associate Director, Clinical Pharmacology and DMPK, Clovis Oncology
Instructor Biographies:
John Erve, PhD, DABT, Jerve Scientific Consulting, Inc.
John
Erve is from Chicago and received degrees in Chemistry (BS, MS) from the University of Chicago and earned a PhD in Toxicology at Oregon State University under the supervision of Dr. Donald Reed. Following postdoctoral work at Vanderbilt (1995-1999)
he joined BD-Biosciences (Woburn, MA) as a Study Director. In 2002, he joined AstraZeneca (Sweden) where he was involved in characterizing reactive metabolites and their protein adducts in an effort to better understand the role of reactive intermediates
in drug toxicity. In 2004 he joined Wyeth (Collegeville, PA) as a Principal Scientist responsible for metabolite identification. Following the merger with Pfizer in 2010, John joined Novartis Institutes of Biomedical Research (Cambridge, MA) as a
Lab Head in Analytical Sciences. John returned to the field of drug metabolism by joining Elan Pharmaceuticals (San Francisco, CA) in 2012 and after Elan was sold, created Jerve Scientific Consulting focusing on helping small biotech companies in
the Bay area with their drug discovery efforts. His research interests include mechanistic toxicology and using mass spectrometry to characterize metabolites and metabolic pathways.
Michelle Liao, PhD, Associate Director, Clinical Pharmacology and DMPK, Clovis Oncology
Michelle Liao is
an Associate Director of Clinical Pharmacology and Drug Metabolism and Pharmacokinetics (DMPK) at Clovis Oncology. Prior to that, she was a Senior Scientist and group leader of DMPK at Takeda Pharmaceuticals International Co. since June 2007. She
was responsible for the in vitro permeability and transport studies to support projects at all stages of discovery and development. She obtained her Ph.D. degree in Molecular Biology and Biochemistry from Peking Union Medical College, and
did her postdoctoral research at Dr. Maria Almira Correia’s lab at University of California, San Francisco (UCSF).
Training Seminar Information
Each CHI Training Seminar offers 1.5 days of instruction with start and stop times for each day shown above, and on the Event-at-a-Glance published in the onsite Program & Event Guide. Training Seminars
will include morning and afternoon refreshment breaks, as applicable, and lunch will be provided to all registered attendees on the full day of the class.
Each person registered specifically for the training seminar will be provided with a hard
copy handbook for the seminar in which they are registered. A limited number of additional handbooks will be available for other delegates who wish to attend the seminar, but after these have been distributed, no additional books will be available.
Though CHI encourages track hopping between conference programs, we ask that Training Seminars not be disturbed once they have begun. In the interest of maintaining the highest quality learning environment for Training Seminar attendees, and because Seminars
are conducted differently than conference programming, we ask that attendees commit to attending the entire program, and not engage in track hopping, as to not disturb the hands-on style instruction being offered to the other participants.
Training Seminar Information
Each CHI Training Seminar offers 1.5 days of instruction with start and stop times for each day shown above and on the Event-at-a-Glance published in the onsite Program & Event Guide. Training Seminars will include morning and afternoon refreshment
breaks, as applicable, and lunch will be provided to all registered attendees on the full day of the class.
Each person registered specifically for the Training Seminar will be provided with a hard copy handbook for the seminar in which they are registered. A limited number of additional handbooks will be available for other delegates who wish to attend
the seminar, but after these have been distributed, no additional books will be available.
Though CHI encourages track hopping between conference programs, we ask that Training Seminars not be disturbed once they have begun. In the interest of maintaining the highest quality learning environment for Training Seminar attendees, and because
seminars are conducted differently than conference programming, we ask that attendees commit to attending the entire program, and not engage in track hopping, as to not disturb the hands-on style instruction being offered to the other participants.
