Structural alert/reactive metabolite concept as applied in medicinal chemistry to mitigate the risk of idiosyncratic drug toxicity: a perspective based on the critical examination of trends in the top 200 drugs marketed in the United States.

@article{Stepan2011StructuralAM,
  title={Structural alert/reactive metabolite concept as applied in medicinal chemistry to mitigate the risk of idiosyncratic drug toxicity: a perspective based on the critical examination of trends in the top 200 drugs marketed in the United States.},
  author={Antonia F Stepan and Daniel P Walker and Jonathan N. Bauman and David A. Price and Thomas A Baillie and Amit S Kalgutkar and Michael D Aleo},
  journal={Chemical research in toxicology},
  year={2011},
  volume={24 9},
  pages={1345-410}
}
Because of a preconceived notion that eliminating reactive metabolite (RM) formation with new drug candidates could mitigate the risk of idiosyncratic drug toxicity, the potential for RM formation is routinely examined as part of lead optimization efforts in drug discovery. Likewise, avoidance of "structural alerts" is almost a norm in drug design. However, there is a growing concern that the perceived safety hazards associated with structural alerts and/or RM screening tools as standalone… CONTINUE READING