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. 2018 Aug 13;8:12046. doi: 10.1038/s41598-018-30509-3

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© The Author(s) 2018

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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BET and CDK2,7 and 9 inhibition work synergistically in BL. (A) Relative viability data indicates synergistic drug interactions between SNS-032 and OTX015. IC50 curves for OTX015 (blue) and SNS-032 (green) as single agents show lower toxicity compared to the IC50 of the combination of SNS-032 (in 10 concentrations) and OTX015 at 200 nM (red). (B) Boxplot of combination indices for SNS-032 and OTX015 in 18 cell lines. (C) Relative viability (%) data in a 10 × 10 matrix experiment (mean of duplicate values) for combinations of OTX015 with SNS-032. Drugs and respective concentrations are listed on x and y-axis. The effect on viability is colour coded (green high viability, red low viability). The diagonal box marks viability data used for constant-concentration-ratio analysis of drug interaction, which resulted in the Fa-CI plots (Fraction affected combination index³⁵). We confirmed synergy in Namalwa and Raji using viability gradient in a 10 × 10 matrix and Fa-CI plots. For Namalwa most combination index values lay below the CI = 1 line, which indicates dose-dependent synergy of the combination of OTX015 and SNS-032. For Raji all data points lie below the horizontal line, which indicates strong synergy.