Abstract

Optimizing chemical structures to create potentially safe drugs during discovery and early development relies on a combination of predictive algorithms, screening, formal toxicology studies, and early clinical trials. Early in the process three critical questions emerge that must be answered by a detailed profiling approach. These questions are: 1) is there a correlation between the chemical structure and potential toxicity that can be used to optimize structures of lead compounds, 2) can specific markers of potential toxicity can be identified early and used as mechanistic decision-making screens, and 3) will exposures (plasma levels) in animal studies correlate with exposures encountered in the clinic thereby providing coverage for safety? Depending on the therapeutic class of compounds being considered and the level of knowledge available, feedback loops of information can be established to guide the development process.

Keywords: Toxicity, Pharmaceuticals, Toxicants