Reactive Metabolites in Drug Discovery and Development: A Critical Examination of the Issues



Wednesday, August 18
11:30 am - 1:00 pm EST


John C Erve, Ph.D., D.A.B.T., Independent Pharmaceutical Research Consultant, Former Principal Research Scientist II, Pfizer Inc.
Course Description
Many drugs withdrawn from the market for toxicity reasons have later been shown to undergo bioactivation to reactive intermediates.  Still, there remain unanswered questions regarding the relationship between reactive metabolites and idiosyncratic toxicity.  For example, although the issue of protein binding has been recognized for decades, the exact mechanisms leading to drug toxicity are still being worked out.  Strategies that medicinal chemists employ in designing drugs with the best safety profile should incorporate our current understanding of structure-toxicity relationships and should also reflect our knowledge about the relationship of dose and risk of idiosyncratic toxicity.  Newer tools such as in silico modeling of drug metabolism can also address bioactivation issues and may be a valuable tool to help design safer drugs.

Learning Objectives

  • Bioactivation pathways that lead to reactive metabolites
  • Toxicophores and Structural Alerts
  • Evidence linking reactive metabolites and Idiosyncratic drug toxicity
  • Reactive metabolites and covalent protein binding
  • In silico tools to address bioactivation


Who Should Attend

  • Bench level scientists interested in understanding the significance of reactive metabolites
  • Medicinal chemists, toxicologists and drug metabolism scientists
  • Drug discovery project leaders, especially first-timers
  • Academic researchers interested in understanding the role of drug metabolism to toxicity
  • Non-scientists managing drug discovery efforts who want to have a deeper understanding of the science involved in drug discovery and development.

Instructor Biography
John is a pharmaceutical professional with 15 years of diverse scientific experience encompassing drug discovery and early clinical development, primarily in the area of drug biotransformation. As a former member of the Biotransformation Group at Pfizer, he was involved in performing metabolite identification studies of over a dozen compounds for advancement to clinical development. He has extensive experience using mass spectrometry to identify metabolites in preclinical toxicology species as well as from first in human studies.
John received his Ph.D. in Toxicology from Oregon State University, and completed a postdoctoral fellowship in the Dept. of Pathology at the Vanderbilt University School of Medicine and center for Molecular Toxicology. He is the author of numerous publications and is also a Diplomat of the American Board of Toxicology.

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