Identification of potential aryl hydrocarbon receptor ligands by virtual screening of industrial chemicals

We have developed a virtual screening procedure to identify potential ligands to the aryl hydrocarbon receptor (AhR) among a set of industrial chemicals. AhR is a key target for dioxin-like compounds, which is related to these compounds’ potential to induce cancer and a wide range of endocrine and immune system-related effects. The virtual screening procedure included an initial filtration aiming at identifying chemicals with structural similarities to 66 known AhR binders, followed by 3 enrichment methods run in parallel. These include two ligand-based methods (structural fingerprints and nearest neighbor analysis) and one structure-based method using an AhR homology model. A set of 6445 commonly used industrial chemicals was processed, and each step identified unique potential ligands. Seven compounds were identified by all three enrichment methods, and these compounds included known activators and suppressors of AhR. Only approximately 0.7% (41 compounds) of the studied industrial compounds was identified as potential AhR ligands and among these, 28 compounds have to our knowledge not been tested for AhR-mediated effects or have been screened with low purity. We suggest assessment of AhR-related activities of these compounds and in particular 2-chlorotrityl chloride, 3-p-hydroxyanilino-carbazole, and 3-(2-chloro-4-nitrophenyl)-5-(1,1-dimethylethyl)-1,3,4-oxadiazol-2(3H)-one. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11356-017-0437-9) contains supplementary material, which is available to authorized users.