Probing the chemical-biological relationship space with the Drug Target Explorer

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 potential space of drugs and biological screening model combinations. To address these challenges, we developed an interactive web application that enables exploration of the chemical-biological interaction space. Compound-target interaction data from public resources were quantified for over 280,000 molecules. Each molecule was annotated with a name and chemical structure, and every target was annotated with gene identifiers. The Drug-Target Explorer allows users to query molecules within this database of experimentally-derived and curated compound-target interactions and identify structurally similar molecules. It also enables network-based visualizations of the compound-target interaction space, and incorporates comparisons to publicly-available in vitro HTS datasets. Users can also identify compounds given one or more targets of interest. 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.