In silico methods to predict drug toxicity

• In silico models facilitate the expert to evaluate toxicity, analyzing results of a battery of models.
• In silico models can address among others, the presence of structural alerts, ADME processes and binding to receptors.
• The validity of in silico models depends on the availability of data, since these methods are basically statistical methods.
• In silico models are nowadays used in an integrated way, providing different insights into toxicity phenomena.

This review describes in silico methods to characterize the toxicity of pharmaceuticals, including tools which predict toxicity endpoints such as genotoxicity or organ-specific models, tools addressing ADME processes, and methods focusing on protein–ligand docking binding.These in silico tools are rapidly evolving. Nowadays, the interest has shifted from classical studies to support toxicity screening of candidates, toward the use of in silico methods to support the expert. These methods, previously considered useful only to provide a rough, initial estimation, currently have attracted interest as they can assist the expert in investigating toxic potential. They provide the expert with safety perspectives and insights within a weight-of-evidence strategy. This represents a shift of the general philosophy of in silico methodology, and it is likely to further evolve especially exploiting links with system biology.