In addition to in vitro and in vivo methods, in silico methods can enhance serendipity and help to rationalize phenomena that experimental methods alone cannot explain. For example, serendipity in drug design can lead to unexpected but potentially positive results, as exemplified by the discovery of Lyrica (pregabalin) . An excellent opportunity for ligand-based methods to enhance compound comparisons is through the addition or augmentation [15] of chemical and physicochemical property data, of in vitro, in vivo, and 'omics' biological data, and of preclinical, clinical, and post-marketing pharmacovigilance data. The added information would support the development of a comprehensive similarity searching capability that would likely, in specific instances, be able to identify chemical mimetics capable of reverting disease signatures. For example, drug-design procedures might be developed for reversing (or preventing) molecular pathway alterations or for predicting toxicity or safety issues for marketed drugs .