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. 2017 Oct 6;7:12758. doi: 10.1038/s41598-017-12630-x

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© The Author(s) 2017

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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Activity of mIDH1 inhibitors in 3D cellular spheroids. (A) Representative images of 3D cellular spheroids of HT1080 (top left), JJ012 (top right), U87 (R132H) (bottom left), and RBE (bottom right) cells (scale = 500 µm). (B) Concentration of 2-HG in media produced from 3D cellular spheroid cultures after 4 days. Bars represent average and SD of 2-HG concentrations determined by MS analysis (n = 12). Dose-response analysis of mIDH1 inhibitor effects on 2-HG production in (C) HT1080(R132C), (D) U87(R132H), (E) JJ012(R132G), (D) RBE(R132S) 3D cellular spheroids (n = 3). (G) Heat map of Log IC₅₀ values of mIDH1 inhibitors from the four 3D cellular spheroids. Cell line dendrogram was generated using the UPGMA clustering method with Euclidean distance measures. (H) Comparison of mIDH1 inhibitor Log IC₅₀ values between 2D and 3D HT1080 (R132C) cellular assays show a strong correlation (R² = 0.95, P value = < 0.0001). (I), Comparison of mIDH1 inhibitor Log IC₅₀ values between 2D and 3D U87 (R132H) cellular assays show a strong correlation (R² = 0.86, P value = 0.0009).