Date: July 17, 2018
Speaker: T. Eric Ballard, PhD, Pfizer
Title: Applications of a micropatterned cocultured (MPCC) hepatocyte system to support small molecule drug discovery
Educational Needs Statement: This symposium is intended to provide an overview of how a human and preclinical species micropatterned cocultured (MPCC) hepatocyte system can be used to better investigate the metabolism and clearance mechanisms of small molecules in drug discovery.
Date: July 17, 2018
Time: 07:30 - 08:30
Speaker: Ray Cooke, Principal Scientist
Title: Radiolabelled ADME Studies of Large Molecules: What are the Options?
Educational Needs Statement
This symposium is intended to provide an overview of the options available to pharmaceutical/biotech companies when considering ADME studies for large molecule entities being developed for therapeutic use.
Title: Use of modified cell lines to study drug permeability and transport.
Proposed Speaker: Scott Hauser, Senior Scientist at MilliporeSigma, In Vitro Safety Systems Group
Educational Needs Statement: This symposium is intended to present on MilliporeSigma’s engineered cell based models for predictive ADME Tox assays with the intestinal and kidney cell lines.
Title: Metabolic Profiling in Early Drug Discovery: Comparison of Hepatocyte and S9 Cocktail Strategies for Assessment of Species-Dependent Metabolism
Proposed Speaker(s): Kevin Kennedy and Shantanu Roychowdhury
Educational Needs Statement:
Drugs that undergo biotransformation in vivo may produce pharmacologically active or chemically reactive metabolites which can result in unexpected effects or potential toxicities. With increased emphasis on testing earlier in development, reducing costs and improving drug attrition, participants will learn the importance of employing effective metabolic profiling tools early in development to aid in predicting human outcomes.
This symposium will highlight strategies and solutions for addressing metabolite identification and profiling issues early in drug discovery. This involves strategies around screening compounds early in drug discovery using various test systems, including, S9 liver and intestinal fractions supplemented with co-factors (cocktail method), hepatocytes, and from relevant species, enabling effective characterization of metabolic products of a drug compound.
Target Audience: DMPK Scientists, Laboratory Leads, Regulatory Scientists
In this symposium, we address the importance of early metabolic profiling for new molecular entities in drug discovery. We will discuss how identification of metabolites can further elucidate potential routes of elimination or identify toxic metabolites that can be early indicators of adverse events. Cross-species metabolic profiling is also valuable for selection of a non-human model for pre-clinical safety testing, as outlined in the recent FDA Guidance for Industry, Safety Testing of Drug Metabolites. Our presentation will include an overview of in vivo drug metabolism, including phase I reactions, mainly involving enzymes (e.g., Cytochrome P450’s) that catalyze the functionalization of a compound (e.g. oxidation) and phase II reactions, whereby enzymes such as UGT’s, SULT’s, and GST’s catalyze the conjugation of compounds. Data will be presented demonstrating the development and validation of a multiple test systems, including, S9 liver and intestinal fractions supplemented with co-factors (cocktail method), hepatocytes, as well as species-dependent differences within these systems that enable effective characterization of metabolic products of a drug compound. The symposium will provide attendees with a good understanding of how employing early screening tools containing robust phase I and phase II metabolism can aid in the effective elucidation of metabolic profiles for new molecular entities.