Mini-Review on Chemical Similarity and Prediction of Toxicity

The notion of similarity relates to a relative comparison between different systems. The process of establishing similarities and analogies by humans is heuristic and subjective. Similarity is a context dependent and a relative measure. It is only meaningful to say that x is similar to y with respect to z. In toxicology and drug design, it is important to have an objective measure of similarity to compare two or more chemicals with respect to their activity or toxicity. Similarity assessment based on structures is a convenient and popular means of comparison but needs to account for each specific activity or toxicity. This mini review starts by providing an overview of the history and philosophy of similarity in general. It describes the different means of quantifying chemicals and how these numerical descriptors can be applied in so-called similarity indices to compare chemicals with respect to their activity or toxicity. The use of a varied wealth of similarity indices applied to the same study case is analyzed and compared throughout.