Identification of estrogen receptor α ligands with virtual screening techniques

Journal of Molecular Graphics & Modelling
Sanna P NiinivehmasOlli T Pentikäinen

Abstract

Utilization of computer-aided molecular discovery methods in virtual screening (VS) is a cost-effective approach to identify novel bioactive small molecules. Unfortunately, no universal VS strategy can guarantee high hit rates for all biological targets, but each target requires distinct, fine-tuned solutions. Here, we have studied in retrospective manner the effectiveness and usefulness of common pharmacophore hypothesis, molecular docking and negative image-based screening as potential VS tools for a widely applied drug discovery target, estrogen receptor α (ERα). The comparison of the methods helps to demonstrate the differences in their ability to identify active molecules. For example, structure-based methods identified an already known active ligand from the widely-used bechmarking decoy molecule set. Although prospective VS against one commercially available database with around 100,000 drug-like molecules did not retrieve many testworthy hits, one novel hit molecule with pIC50 value of 6.6, was identified. Furthermore, our small in-house compound collection of easy-to-synthesize molecules was virtually screened against ERα, yielding to five hit candidates, which were found to be active in vitro having pIC50 values from ...Continue Reading

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Citations

Mar 31, 2016·International Journal of Environmental Research and Public Health·Huixiao HongWeida Tong
Jul 13, 2016·Journal of Receptor and Signal Transduction Research·Guy LeclercqYves Jacquot
Apr 6, 2018·Journal of Enzyme Inhibition and Medicinal Chemistry·Sanna NiinivehmasOlli T Pentikäinen
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Jun 9, 2019·International Journal of Molecular Sciences·Mira AhinkoPekka A Postila
Jul 2, 2019·Chemical Biology & Drug Design·Elmeri M JokinenOlli T Pentikäinen
Oct 9, 2019·Molecular Neurobiology·Pekka A Postila, Tomasz Róg
Jun 18, 2020·International Journal of Molecular Sciences·Divya BafnaArtem Cherkasov
Aug 6, 2020·International Journal of Molecular Sciences·Mari Ishigami-Yuasa, Hiroyuki Kagechika
Jun 5, 2018·Oxidative Medicine and Cellular Longevity·Xiaocong PangGuan-Hua Du
Mar 20, 2018·Frontiers in Chemistry·Sanna RauhamäkiOlli T Pentikäinen
Jun 10, 2020·Current Topics in Medicinal Chemistry·Rodrigo Santos Aquino de AraújoFrancisco Jaime Bezerra Mendonça-Junior
Jan 12, 2021·Saudi Journal of Biological Sciences·Jesudass Joseph SahayarayanAmalorpavanaden Nicholas Daniel
Mar 30, 2021·Heliyon·Shweta JakhmolaHem Chandra Jha

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