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. 2020 Oct 15;10:17472. doi: 10.1038/s41598-020-74346-9

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© The Author(s) 2020

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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.

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TEC-1 is structurally similar to SMN-C3 or risdiplam and modulates SMN2 splicing. (a) Pharmacophore model and alignment of TEC-1 (green), risdiplam (pink), and SMN-C3 (blue) with MOE2018.01. Pharmacophore annotation: Aromatic and other pi-system rings (orange), H-bond donor heavy atom (magenta), H-bond acceptor heavy atom (pale blue). (b) Structure of TEC-1. (c) Structure of SMN-C3. (d) Structure of risdiplam. (e) qPCR analysis of FL-SMN2 transcripts in SMA type II fibroblasts (GM03813) exposed to each compound for 24 h. The amounts of mRNA were normalized to those of GAPDH. (f) qPCR analysis of Δ7 transcripts of GM03813 cells exposed to each compound for 24 h. The amounts of mRNA were normalized to those of GAPDH. Data are from two biologically independent samples in e, f. a-d were derived by by Axcelead Drug Discovery Partners, Inc.