Institute of Biomolecular Chemistry (ICB), Consiglio Nazionale delle Ricerche (CNR), Via Campi Flegrei 34, I-80078, Pozzuoli, Napoli, Italy; Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084, Fisciano, SA, Italy.
Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084, Fisciano, SA, Italy.
Eur J Med Chem. 2018 May 25;152:253-263. doi: 10.1016/j.ejmech.2018.04.018. Epub 2018 Apr 12.
Inverse Virtual Screening (IVS) is a docking based approach aimed to the evaluation of the virtual ability of a single compound to interact with a library of proteins. For the first time, we applied this methodology to a library of synthetic compounds, which proved to be inactive towards the target they were initially designed for. Trifluoromethyl-benzenesulfonamides 3-21 were repositioned by means of IVS identifying new lead compounds (14-16, 19 and 20) for the inhibition of erbB4 in the low micromolar range. Among these, compound 20 exhibited an interesting value of IC on MCF7 cell lines, thus validating IVS in lead repurposing.
反向虚拟筛选（IVS）是一种基于对接的方法，旨在评估单个化合物与蛋白质文库相互作用的虚拟能力。我们首次将这种方法应用于一系列合成化合物，这些化合物对其最初设计的靶点没有活性。通过 IVS，三氟甲基苯磺酰胺 3-21 被重新定位，发现了新的抑制 erbB4 的先导化合物（14-16、19 和 20），其抑制活性达到低微摩尔范围。其中，化合物 20 在 MCF7 细胞系中表现出有趣的 IC 值，从而验证了 IVS 在先导化合物重新定位中的应用。
