MEDI 222 |
| Some drugs either have been removed from the market, or have been labeled with "black box" warnings because they have caused life-threatening toxic effects. Most of these toxicities are idiosyncratic, and evidence suggests that most are caused by reactive metabolites. Over the past 25 years, knowledge has accumulated concerning chemical substructures that form reactive metabolites, which will be one focus of this presentation. A second focus will be a discussion of two general approaches that some pharmaceutical companies are using in their discovery and development programs to help make benefit/risk decisions concerning drug candidates. One approach uses methodologies (e.g. covalent binding) that can be said to rapidly, but crudely, assess reactive metabolite interactions with cellular proteins. Other approaches utilize "omic" technologies to assess possible effects of reactive metabolites on dysregulation of various cellular regulatory pathways. Examples of each approach will be highlighted with examples. Finally, there will be some discussion of the advantages and disadvantages of each approach, and how some improvements to each might yield information that is more revealing concerning mechanisms of toxicity. |
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Drug Safety
9:00 AM-12:00 PM, Tuesday, August 21, 2007 BCEC -- 210A, Oral
Division of Medicinal Chemistry |