Polypharmacology prediction: the long road toward comprehensively anticipating small-molecule selectivity to de-risk drug discovery.

Polypharmacology prediction has made impressive progress over the last decades and contributed to identify many off-targets. However, data incompleteness currently limits most approaches to comprehensively predict selectivity. Moreover, our limited agreement on model assessment challenges the identification of the best algorithms - which at present show modest performance in prospective real-world applications. Despite these limitations, the exponential increase of multidisciplinary Big Data and AI hold much potential to better polypharmacology prediction and de-risk drug discovery.