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. 2019 May 13;9:7260. doi: 10.1038/s41598-019-43677-7

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Identification of the binding site. Molecular docking model of IQM-PC332 (a) and IQM-PC330 (b) in complex with DREAM. Amino acids within 4 Å of the ligand are shown; yellow dashed lines indicated hydrogen bonds. For clarity non-polar hydrogens are not shown. (c) Direct binding of IQM-PC332 and IQM-PC330 in SPR assays to immobilized wtDREAM compared to Tyr118Ala and Tyr130Ala DREAM mutants. (d) Comparative response of sensitized STHdhQ^111/111 cells to H₂O₂-induced oxidative stress after overexpression of wild type, Tyr118Ala or Tyr130Ala DREAM. One-way ANOVA with Holm-Sidak’s multiple comparison test (n = 6). ****p < 0.0001, *p < 0.05 vs empty vector (LV). (e) Effect of vehicle (DMSO), 130 nM IQM-PC332 or 40 nM IQM-PC330 in wild type DREAM- (DREAM) or Tyr130Ala DREAM-sensitized STHdhQ^111/111 cells (Y130A). Control bar represents DREAM- or Tyr130Ala DREAM sensitized STHdhQ^111/111 cells non-exposed to H₂O₂, respectively. The concentrations of IQM-PC compounds used in these experiments correspond to the minimum concentration able to fully reverse the effect of H₂O₂ exposure. Non-parametric Mann-Whitney t-test *p < 0.05 vs corresponding compound in wild type DREAM sensitized STHdhQ^111/111 cells.