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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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Acute potentiation of CFTR by elexacaftor (VX-445) in primary-derived non-CF human nasal epithelia. (A) Representative I_t recordings showing response to acute additions of amiloride (100 µM), DMSO, VX-445 (100 nM), Fsk (20 µM)/IBMX (100 µM), and/or CFTR_inh-172 (100 µM). Acute additions indicated by a letter (X, Y, Z…) correspond to interventions listed in the key in Panel A. (B) Changes in I_t after the additions of test compounds for the experiment presented in Panel A. (C) Change in I_t after acute addition Y, demonstrating the CFTR-specific potentiation of VX-445. (D) Intracellular cAMP after 30 min exposure to DMSO, Fsk, or VX-445. (E) Sidedness of immediate (within 5 min) action of VX-445 compared to DMSO controls. (F) Concentration–response curve for VX-445 and other CFTR correctors, tezacaftor (VX-661) or lumacaftor (VX-809). Only VX-445 significantly increased I_t compared to a DMSO control (denoted by asterisks; EC₅₀: 1.50 ± 1.40 nM). See Supplementary Materials 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 < 0.01; ***P < 0.001.