Reactive metabolite formation prediction

To date, there are no examples where in silico tools have been utilized in a proactive fashion to predict reactive metabolite formation with small molecules. There are virtual or experimental techniques that can predict metabolic outcomes including the potential for forming reactive metabolites to some degree or the other. At best, these techniques have been used to rationalize published experimental observations on bioactivation pathways. Exploitation of these tools in drug discovery in a proactive fashion would necessitate additional experimental studies to validate the predictions. 

Liability assessments can be based on structural features (e.g., known tox-ophores or structural features leading to the formation of reactive metabolites) or predictive models for liability targets, like the hERG channel [44] or CYP inhibition [45]. 

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