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. 2021 Oct 6;11:19810. doi: 10.1038/s41598-021-99184-1

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© The Author(s) 2021, corrected publication 2021

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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Synergism of ivacaftor (VX-770) and elexacaftor (VX-445) in potentiating G551D-CFTR in HNE cells. (A) Representative I_t recordings of G551D-HNE cells showing acute actions of VX-770 and VX-445. (B–C) Changes in I_t after acute addition of VX-770 in the absence and presence of VX-445 (B) and in response to the acute addition of VX-445 in the absence and presence of VX-770 (C). (D–E) Changes in I_t after the additions of test compounds for the experiment presented in (A). G551D-CFTR mediated I_t is greatest after acute potentiation by both VX-770 and VX-445. (F) Representative I_t recordings of G551D-HNE treated for 24 h with DMSO, the double combination of VX-770 and VX-445, or the triple combination of VX-661, VX-770, and VX-445 (i.e., Trikafta). (G) CFTR_inh-172 inhibited I_t for the experiment presented in (F). See SI for additional experimental details and for supporting data. All data are presented as mean ± standard error. Bars with different letters (A, B, C…) are significantly different from each other (ANOVA; P < 0.05). Asterisks indicate specific P values: ****P < 0.0001.