Understanding and avoiding safety risks associated with Toxicophores and Structure Alerts

Speaker

Instructor: Bryan Norman
Product ID: 706327

Location
  • Duration: 60 Min
Structure Alerts, also known as toxicophores, are classes of chemicals, functional groups or substructures that, when present in drugs or drug candidates, have been linked to preclinical toxicity and/or adverse drug reactions in humans. This webinar will define and describe many of those structure alerts and outline the mechanisms that have been associated with their toxicity. Mitigation strategies will also be discussed.
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Why Should You Attend:

Are you and others in your organization aware of the many mechanisms in which structure alerts can induce risks in drug discovery? This webinar will highlight the most common structure alerts associated with preclinical and clinical toxicity and demonstrate appropriate mitigation strategies that can be used to lessen those risks and identify safer drug candidates.

Structure Alerts, also known as Toxicophores, are classes of chemicals, functional groups or substructures that, when present in drugs or drug candidates, have been linked to adverse drug reactions (ADRs). Structure alerts have been known to impart ADR risks via multiple mechanisms, some of which are directly associated with the structure of the drug and some that require metabolic activation (bioactivation) of the drug to form an offending metabolite. Some Structure Alerts are inherently electrophilic or are polycyclic aromatic structures that are known to bind to DNA. However, the most common are compounds that undergo metabolic bioactivation to produce electrophilic reactive metabolites that can bind to endogenous nucleophiles, such as proteins or nucleic acids, resulting in ADRs. This webinar will define and describe many of those structure alerts and outline the mechanisms that have been associated with their toxicity. Mitigation strategies will also be discussed.

While the focus is on medicinal chemistry methods, this webinar will benefit all scientists who participate in the cross functional execution of drug discovery programs.

Areas Covered in the Webinar:

  • Identification and description of Structure Alerts
  • Mechanisms whereby Structure Alerts induce risk
    • Inherent chemical reactivity
    • Bioactivation and formation of reactive metabolites
    • Structures that bind DNA
  • Assays used to detect and characterize risks associated with Structure Alerts
  • Emerging industry strategies to mitigate risks associated with structure alerts
    • Avoidance and replacement
    • Mitigation of bioactivation pathways
    • Tuning steric and electronic effects
    • Metabolic switching

Who Will Benefit:

  • Medicinal chemists, toxicologists, biologists, pharmacologists, pharmacokineticists and program managers will all gain valuable insights into modern preclinical safety assessment and mitigation strategies.
  • Educational levels: B.S., M.S., Ph.D.
  • Best suited for drug discovery researchers in early to mid career.

Free Materials:

  • Reference documents
  • Rule documents or guidance
  • Checklist
  • SOP template
  • Easy fill in forms
  • Articles
Instructor Profile:
Bryan Norman

Bryan Norman
President, Norman Drug Discovery Training and Consulting LLC

Bryan H. Norman received his Ph.D. in Organic Chemistry at Emory University and was an NIH Postdoctoral Fellow at Penn State University. After three years at Monsanto/Searle, Bryan joined Eli Lilly and Company in 1993, where he led multiple cross functional drug discovery efforts, many of which culminated in clinical candidates for oncology, endocrine and pain indications. In addition to his expertise in medicinal chemistry, Bryan has significant cross functional drug discovery experience and expertise in additional disciplines, such as biomarkers, pharmacokinetic/pharmacodynamic (PK/PD) relationships, mechanisms of drug metabolism and toxicology. He has specific expertise in the mechanisms and mitigation strategies to avoid drug-induced liver injury (DILI). The breadth of his background has led to his service on many Due Diligence teams to assess potential in-license opportunities. In addition to drug discovery training and consulting activities, Bryan is currently an Adjunct Professor at the Indiana University School of Medicine, where he teaches multiple drug discovery topics. He is a Volume Editor and serves on the Editorial Board of Burger’s Medicinal Chemistry, Drug Discovery and Development. Bryan is currently on the Board of Directors of the Medicinal and Bioorganic Chemistry Foundation and serves on various grant review committees. He has published over 45 papers in peer-reviewed scientific journals, been named an inventor on over 30 U.S. patents and given many invited lectures at scientific conferences and universities. His most recent research interests have focused on the identification of mechanisms associated with drug-induced liver injury and the discovery of novel analgesic agents for use in chronic pain.

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