Discussion

There is increasing interest in applying in vitro methods to characterize the potential toxicity of drugs and chemicals. While data-driven approaches to build predictive models can be helpful for risk assessment, the ability to inform an in depth understanding of toxicity mechanisms is highly advantageous as this increases confidence in the predicted outcomes. Here we describe a chemical biology approach for elucidating potential toxicity mechanisms for thrombosis-related side effects in humans. This effort takes advantage of a large chemical biology data set comprising the effects of a large collection of known, well-characterized reference compounds and drugs on the levels of tissue factor (TF) in a primary human endothelial cell-based model of vascular inflammation, the BioMAP® 3C system.