Mechanisms of Chemically-Induced Toxicity for Medicinal Chemistry
May 18 - 20, 2008 | The Sheraton Society Hill| Philadelphia, PA
Overview
Conference chairs F. Peter Guengerich, Professor of Biochemistry and the Director of Vanderbilt’s Center in Molecular Toxicology, and Dr. James MacDonald, EVP of Preclinical Development at the Schering-Plough Research Institute, have developed this program to cover the chemical basis of toxicity as it applies to medicinal chemistry.
Sessions will be held on reactive metabolites and alternative mechanisms, with an emphasis on specific chemical groups and methods of screening. Numerous case studies will be given throughout the program by scientists from Pfizer, Schering Plough, and Merck, among others.
The conference will also cover some newer methods and even future approaches to assessing the toxicity potential of compounds in humans, including “omics” approaches, and will provide a view of the current regulatory environment -- and therefore the level of likely acceptance of those methods.
On Sunday, a one-day short course will be offered, designed to get participants up to speed on the subject matter that the conference covers. Topics will include: the essentials of drug metabolism and pharmacokinetics; enzymes involved in drug metabolism (both human & animal) and their relevance to drug interactions and toxicity; covalent binding, and an overview of related biology and its relevance to toxicity; and examples of approaches with drugs: defining mechanisms, developing new screens, and using chemical synthesis to improve the probability of success.
Speakers
Keynote
Gerald Miwa, formerly of Millennium
Reactive Metabolite-Mediated Toxicity
Kaushik Mitra, Department of Drug Metabolism and Pharmacokinetics, Merck on “Minimizing Metabolic Activation during Pharmaceutical Lead Optimization: Progress, Gaps and Future Directions”
Amit Kalgutakar of Pfizer on “Chemical Toxicophores and Their Potential for Trouble”
Mike Freeman, Prof. Radiation Oncology, Radiology, Cancer Biology at Vanderbilt University School of Medicine on “Coupling LC/MS/MS analysis with biochemical and cell biology-based approaches to identify reactive Keap1 cysteine residues that are critical for function: Insights into mechanisms regulating induction of Phase II metabolism”
Daniel C. Liebler, Director of the Jim Ayers Institute for Precancer Detection and Diagnosis and Professor of Biochemistry, Pharmacology and Biomedical Informatics at Vanderbilt University School of Medicine on “Covalent adduction of kinase sensors and induction of apoptosis”
Alternative Mechanisms of Chemical Toxicity
Jim Klaunig, Professor & Director of Toxicology; Director, Center for Environmental Health; Associate Director, IU Simon Cancer Centerat Indiana University on “Mechanisms of Epigenetic Carcinogenesis”
Ellen Evans, Senior Director, Clinical Pathology and Immunotoxicology at Schering-Plough Research Institute on “Toxicity of the Immune System: overview and case summaries”
Alan Bass, Senior Fellow at Schering Plough Research Institute on “Identifying Unintended Cardiovascular Toxicity in Discovery and Development of New Molecules”
Steven Duddy, partner and CSO, Integrated Nonclinical Development Solutions on “Toxicities Associated with PPARs and their Agonists: Considerations for Human Risk Assessment”
Human Risk Assessment of Chemically-Mediated Toxicity
Tom Begley of SUNY Albany on “Systems Biology and Functional Genomics Approaches for the Identification of Cellular Responses to Toxicants”
Bill Schaefer of Merck on “Proteomics and Metabolomics in Safety Assessment”
Rusty Thomas of the Hamner Institute/CIIT on “The Application of Transcriptomic Technology for Evaluating the Tumorigenic Potential of Chemicals”
Future Approaches to Assessment of Toxic Potential
John Bucher, Associate Director, National Toxicology Program at the National Institute of Environmental Health Sciences (NIEHS), on “Transforming Environmental Health Protection”
David Jacobson-Kram of the Office of New Drugs/Center for Drug Evaluation and Research at the FDA on where the field is going and the relative value of some of the newer technologies
Jiri Aubrecht of Pfizer on the future of tox testing