PROMISCUOUS 2.0: a resource for drug-repositioning

Abstract

The development of new drugs for diseases is a time-consuming, costly and risky process. In recent years, many drugs could be approved for other indications. This repurposing process allows to effectively reduce development costs, time and, ultimately, save patients' lives. During the ongoing COVID-19 pandemic, drug repositioning has gained widespread attention as a fast opportunity to find potential treatments against the newly emerging disease. In order to expand this field to researchers with varying levels of experience, we made an effort to open it to all users (meaning novices as well as experts in cheminformatics) by significantly improving the entry-level user experience. The browsing functionality can be used as a global entry point to collect further information with regards to small molecules (∼1 million), side-effects (∼110 000) or drug-target interactions (∼3 million). The drug-repositioning tab for small molecules will also suggest possible drug-repositioning opportunities to the user by using structural similarity measurements for small molecules using two different approaches. Additionally, using information from the Promiscuous 2.0 Database, lists of candidate drugs for given indications were precomputed, including a section dedicated to potential treatments for COVID-19. All the information is interconnected by a dynamic network-based visualization to identify new indications for available compounds. Promiscuous 2.0 is unique in its functionality and is publicly available at http://bioinformatics.charite.de/promiscuous2.

Figure 1.

Schema showing the different resources (A) used to create Promiscuous 2.0 and a collection of features such as predicted targets (B), the results of the drug repositioning option (C), an example network (D) and the integrated drug search options (E).

Figure 2.

Network representation of new indication for warfarin. (A) Starting with the indication G20–G26 to explore the database for possible new drugs (1 click to add indication-target interactions); (B), GLUL appears for a common target in the treatment of e.g. Parkinson, which is part of the input indication of A (click two times to add target-drug interactions); (C), one known drug for GLUL is ‘ethyl biscoumacetate’ (search for drug-drug-interactions); (D) by this, warfarin becomes visible. Due to the cheminformatics behaviour of similar structures as well as the fact that drugs affect each other share similar mechanism of actions, it could be suggested for the starting indication from A.