PROMISCUOUS: a database for network-based drug-repositioning

TLDR

Drug approval is slow, costly, and risky, yet accidental multi‑specificity of approved drugs has produced blockbuster repositioning opportunities, and predicting off‑target effects offers a rational basis for understanding side‑effects. The study aims to systematically identify new applications for known drugs. PROMISCUOUS compiles 25,000 drugs—including withdrawn and experimental ones—annotated with 21,500 drug‑protein and 104,000 protein‑protein relationships from public resources, and links drug structural similarity and side‑effect data to protein interaction networks to enable multi‑pharmacology analysis, and is publicly available at bioinformatics.charite.de/promiscuous. The network‑based approach offers a starting point for drug‑repositioning.

Abstract

The procedure of drug approval is time-consuming, costly and risky. Accidental findings regarding multi-specificity of approved drugs led to block-busters in new indication areas. Therefore, the interest in systematically elucidating new areas of application for known drugs is rising. Furthermore, the knowledge, understanding and prediction of so-called off-target effects allow a rational approach to the understanding of side-effects. With PROMISCUOUS we provide an exhaustive set of drugs (25,000), including withdrawn or experimental drugs, annotated with drug-protein and protein-protein relationships (21,500/104,000) compiled from public resources via text and data mining including manual curation. Measures of structural similarity for drugs as well as known side-effects can be easily connected to protein-protein interactions to establish and analyse networks responsible for multi-pharmacology. This network-based approach can provide a starting point for drug-repositioning. PROMISCUOUS is publicly available at http://bioinformatics.charite.de/promiscuous.