Assessing the Potential Toxicity of New Pharmaceuticals，Dale
E. Johnson* and Grushenka H.I. Wolfgang，ddplatform. LLC 6027 Christie Ave.
Emeryville, CA 94608, USA
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.