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SCDMDG presents:

Next Generation NSAIDs That Selectively Inhibit Endocannabinoid Metabolism by COX-2

Tuesday May 6, 2014
Lawrence J. Marnett, Ph.D., F.C.P
Professor of Biochemistry, Chemistry and Pharmacology
Mary Geddes Stahlman Professor of Cancer Research
Director, Vanderbilt Institute of Chemical Biology
Vanderbilt University
Nashville, TN

Lawrence J. Marnett

Dr. Marnett has research interests in the areas of protein structure and function, nucleic acid chemistry, drug design and synthesis, and chemical genomics. Much of his work focuses on the biochemistry and molecular biology of oxidation of natural and synthetic chemicals. Areas of interest include: mechanisms of oxidation of arachidonic acid and endocannabinoids by cyclooxygenase and lipoxygenase enzymes, design, synthesis, and biochemical evaluation of lipoxygenase and selective cyclooxygenase-2 (COX-2) inhibitors; chemistry and biology of DNA damage by lipid oxidation products; and endogenous pathways of DNA damage in the genesis of human cancer.

Cyclooxygenase-2 (COX-2) is the molecular target of non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors. Dr. Marnett's laboratory has combined structural analysis with functional studies to define the molecular determinants of the interaction of ligands (substrates and inhibitors) with COX-2. For example, the lab recently reported the identification of a critical H-bonding interaction that leads to the selectivity of aspirin for acetylation of Ser-530 in COX-2. Many NSAIDs are aralkyl carboxylic acids. Comparative analysis of the effect of site-directed mutation of active site residues on the binding of substrates and inhibitors to COX-1 and COX-2 led us to hypothesize that neutral derivatives of esters and amides would bind selectively to COX-2. They tested this hypothesis by synthesizing a series of neutral derivatives of NSAIDs and demonstrating increases in selectivity for COX-2 of several orders of magnitude. Dr. Marnett is exploiting this discovery to prepare novel COX-2 inhibitors as anti-inflammatory drugs and cancer preventive agents.

Recent publications include:

Date:   Tuesday May 6, 2014 – 5:00 p.m. (Buffet), 7:00 p.m. (Presentation)
Location:   Sanford Consortium for Regenerative Medicine
2880 Torrey Pines Scenic Drive
La Jolla, CA 92037
Price:   $20 Registration in advance or at the door (includes buffet dinner and soft drinks/beer/wine)

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Our May 2014 meeting is generously sponsored by:

Silver Sponsors

Bioreclamation IVT
Optivia Bio
Optivia Bio

Bronze Sponsors


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

Prior presentations:

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Speaker PDF Topic Date
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