Structural Alerts for Toxicity

Abstract This chapter summarizes structural alerts where there is a significant weight of evidence that their incorporation into a drug candidate molecule is likely to result in a higher than average incidence of attrition due to adverse safety/or toxicity findings. The mechanism of formation of reactive metabolites from each structural alert is summarized. The structure–toxicity relationships and the boundary of definition for each structural alert are discussed. The benefits of low exposure and alternative routes of metabolism are highlighted along with screening methods to manage the risks associated with structural alerts.