About The Meeting

The idea that small, unreactive organic compounds could kill cells by undergoing biotransformation to chemically reactive metabolites stems from work done in the laboratory of Dr. Bernard Brodie at the NIH starting in the late 1960s. Since then an avalanche of chemical and biological studies of "covalent binding" has appeared in the literature. Xenobiotic-adducted proteins released by dying cells, as well as those formed by reactive metabolites that escape cells, are found circulating in plasma and are being considered as biomarkers for potential toxicity. These collective findings have significantly influenced the drug development process in industry and regulatory thinking on the part of government agencies. Yet, it is still not clear exactly how cells recognize and react when their proteins experience xenobiotic post-translational modification by chemically reactive metabolites. The talk will present a retrospective over some of the important technical and conceptual advances in the chemistry and biology of reactive metabolites that have occurred since Brodie's seminal work, and some of the questions that remain.

About Dr. Hanzlik

Dr. Hanzlik earned a B.A in Chemistry and Biology from Southern Illinois University ('66) and a Ph.D. in Organic Chemistry from Stanford University ('70) where he worked on the biosynthesis of lanosterol under the direction of Professor Eugene van Tamelen. After a postdoctoral year as a NATO-NSF Fellow in Cambridge working on chemical models for oxygenase enzymes with Professor Jack Lewis, he joined the University of Kansas where he is currently Professor of Medicinal Chemistry.

He is an active member of the scientific community, having served on NIH study sections and Editorial Advisory Boards for several journals. He is a Charter Member and Past President of ISSX and has also held elective office in the SOT and AAAS. In addition he is a member of the ACS, the Royal Society of Chemistry and the Protein Society. He has trained more than 50 graduate and postdoctoral students at Kansas where he currently teaches graduate courses in the physiological aspects of medicinal chemistry and principles of drug design. He also directs a NIH COBRE Center in Protein Structure and Function.

His research interests encompass a broad range of biology and chemistry. His laboratory has been active in the field of drug metabolism and reactive metabolite toxicology for almost 40 years. His work has focused on bromobenzene, thiobenzamide and thioacetamide as model hepatotoxins, with an emphasis on elucidating the structure and reactivity of their chemically reactive metabolites. As this work progressed it evolved to include proteomics for identifying reactive metabolite target proteins and bioinformatics for exploring the connection between protein covalent binding and the resulting cytotoxicity. Outside the lab his main interests are jogging, backpacking and windsurfing.

Our April 2015 meeting is generously sponsored by:

National University

Silver Sponsors

Optivia Biotechnology

Bronze Sponsors

Agilux Laboratories

For more information on sponsoring SCDMDG, please refer to our sponsorship guidelines.

Prior presentations:

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Speaker	PDF	Topic	Date
J. Ernest Simpson, Ph.D.		The Chemistry Of Wine	October 28, 2014
Lawrence J. Marnett, Ph.D., F.C.P		Next Generation NSAIDs That Selectively Inhibit Endocannabinoid Metabolism by COX-2	May 6, 2014
Lawrence J. Lesko, Ph.D., F.C.P.		Drug Interaction Studies: Differences and Similarities in How to Meet the Regulatory Expectations in FDA Guidance and EMA Guidelines	May 14, 2013
Thomas Tozer, Ph.D.		Pharmacokinetics of Protein Drugs	October 23, 2012
Shujuan Chen		Application of Animal Models for Human Glucuronidation	October 23, 2012
Caroline Decker		The Use of Modified Bacterial CYPs for Metabolite Generation	October 23, 2012
Mary Dwyer, Ph.D.		Cancer Therapeutics: A Novel Approach	October 23, 2012
Justin Hoffman PharmD MS		Population Pharmacokinetics (PK) of LopinavirDuring Pregnancy and Postpartum	October 23, 2012
David A. Yee		Observations on the Urine Metabolic Ratio of Oxymorphone to Oxycodone in Pain Patients	October 23, 2012
Nabil Hanna, Ph.D.		The Discovery and Development of Rituxan	April 10, 2012
Dr. Richard Kim		Drug Transporters: In Vitro and Knockout Model Systems, Pharmacogenomics, and Clinical Relevance	April 19, 2011
Dr. Jerry Galluppi		Biotherapeutic Drug Research and Development: A Growing Role for the DMPK Scientist	October 5, 2010
Dr. Dennis Smith		Does drug metabolism hold its future in its own hands?	April 27, 2010
Dr. Paul F. Hollenberg		Mechanism-Based Inactivation of Human Cytochromes P450	October 6, 2009
Dr. Jack H. Dean Dr. Thomas Baillie		Challenges & Opportunities in Drug Development from a Drug Safety and Metabolism Perspective	May 19, 2009
Eric Johnson, Ph.D.		Characterization of Substrate/Inhibitor Binding to Drug-Metabolizing Cytochrome P450 Monooxygenases using X-ray Crystallography	September 30, 2008
Dr. Kenneth E. Thummel, Ph.D.		Regulation Of Intestinal CYP3A By VDR: Implications And Safety Of Oral Therapeutics	May 7, 2008
Dr. Anthony Lu, Ph.D.		Why Is The Liver Microsomal Cytochrome P450 Such A Versatile And Unique Enzyme?	September 12, 2007
Dr. Scott Obach, Ph.D.		Leveraging ADME Data In Metabolites In Safety Testing (MIST)	April 18, 2007
Dr. Sidney Nelson, Ph.D.		Drug Metabolism and Chemical Structural Alerts	September 27, 2006
Richard B. Kim, MD		Relevance and Utility of Transporters to Drug Discovery and Development	September 21, 2005
Dr. Frederick P. Guengerich, Ph.D.		Human Cytochrome P450 2A6 as a Case History:  Flavors, Smoke, Blue Roses, New Drugs & Basics of a P450	April 27, 2005
Dr. Leslie Benet, Ph.D.		Predicting Drug Disposition via Application of BCS: Transport/Absorption/Elimination Interplay and BDDCS	September 29, 2004
Dr. Christopher A. Lipinski, Ph.D.		ADME/Tox: How Low Can You Go And How Do You Recover?	April 21, 2004