Abstract
Modern phenotypic high-throughput screens (HTS) present several challenges including identifying the target(s) that mediate the effect seen in the screen, characterizing ‘hits’ with a polypharmacologic target profile, and contextualizing screen data within the large space of drugs and screening models. To address these challenges, we developed the Drug–Target Explorer. This tool allows users to query molecules within a database of experimentally-derived and curated compound-target interactions to identify structurally similar molecules and their targets. It enables network-based visualizations of the compound-target interaction space, and incorporates comparisons to publicly-available in vitro HTS datasets. Furthermore, users can identify molecules using a query target or set of targets. The Drug Target Explorer is a multifunctional platform for exploring chemical space as it relates to biological targets, and may be useful at several steps along the drug development pipeline including target discovery, structure–activity relationship, and lead compound identification studies.
Highlights
In the modern drug discovery and development process, high-throughput screens (HTS) of drugs have become a common and important step in the identification of novel treatments for disease
Hypothesis generation of targets for newly‐discovered molecules To highlight the use of this app to find potential off-targets of a novel molecule, we queried the Drug–Target Explorer for C21, a recently-published Polo like kinase (PLK) inhibitor that is not captured in our database [34]
Starting at a similarity of 1, we decreased the similarity cutoff until we identified the most similar molecule in the database at a similarity of 0.74 (CHEMBL3609309), a BRD4-binding molecule
Summary
In the modern drug discovery and development process, high-throughput screens (HTS) of drugs have become a common and important step in the identification of novel treatments for disease. DGIdb and ChEMBLSpace cannot be used to explore similar chemical space to the query molecule These two, plus SuperTarget and CarlsbadOne, cannot be queried using molecules that are not in the database; a feature that might help users with novel preclinical candidate drugs. No tools other than STITCH and Probes & Drugs perform gene list enrichment, which may help users interpret the biological MoAs of polypharmacologic molecules These tools do not allow users to evaluate query drugs in the context of publically available high throughput drug screening datasets. To address these gaps, we developed the Drug–Target Explorer.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
