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Open AccessArticle

Computational Study of Drugs Targeting Nuclear Receptors

Faculty of Pharmacy; University of Ljubljana, Aškerčeva cesta 7, SI-1000 Ljubljana, Slovenia
Author to whom correspondence should be addressed.
Academic Editor: Marjan Vračko
Molecules 2020, 25(7), 1616;
Received: 14 March 2020 / Revised: 28 March 2020 / Accepted: 31 March 2020 / Published: 1 April 2020
(This article belongs to the Special Issue Integrated QSAR)
Endocrine-disrupting chemicals have been shown to interfere with the endocrine system function at the level of hormone synthesis, transport, metabolism, binding, action, and elimination. They are associated with several health problems in humans: obesity, diabetes mellitus, infertility, impaired thyroid and neuroendocrine functions, neurodevelopmental problems, and cancer are among them. As drugs are chemicals humans can be frequently exposed to for longer periods of time, special emphasis should be put on their endocrine-disrupting potential. In this study, we conducted a screen of 1046 US-approved and marketed small-molecule drugs (molecular weight between 60 and 600) for estimating their endocrine-disrupting properties. Binding affinity to 12 nuclear receptors was assessed with a molecular-docking program, Endocrine Disruptome. We identified 130 drugs with a high binding affinity to a nuclear receptor that is not their pharmacological target. In a subset of drugs with predicted high binding affinities to a nuclear receptor with Endocrine Disruptome, the positive predictive value was 0.66 when evaluated with in silico results obtained with another molecular docking program, VirtualToxLab, and 0.32 when evaluated with in vitro results from the Tox21 database. Computational screening was proven useful in prioritizing drugs for in vitro testing. We suggest that the novel interactions of drugs with nuclear receptors predicted here are further investigated. View Full-Text
Keywords: endocrine-disrupting chemicals; drugs; databases; nuclear receptors; molecular docking; multidimensional QSAR. endocrine-disrupting chemicals; drugs; databases; nuclear receptors; molecular docking; multidimensional QSAR.
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Kenda, M.; Sollner Dolenc, M. Computational Study of Drugs Targeting Nuclear Receptors. Molecules 2020, 25, 1616.

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