Pharmaceuticals, Volume 16, Issue 12
2023 December - 111 articles
Cover Story: Combining in silico and in vitro approaches allowed us to investigate the mechanism of action as CFTR correctors of three hybrid derivatives (2a, 7a and 7m) featuring the thiazole core tethered to the benzodioxole motif of VX809. Molecular modelling suggested that 2a, 7a and 7m interact with the MSD1/NBD1 interface. Biochemical analyses confirmed these data, showing that the three molecules affect the expression and stability of the F508del NBD1. We tested the ability of combinations of 2a, 7a and 7m with correctors already in clinical use to increase the activity of the F508del CFTR channel. We used VX661, a class I corrector binding to MSD1, and VX445, increasing the expression and stability of MSD2. A YFP assay was applied to confirm the additive influence of 2a, 7a and 7m on F508del CFTR function to that of VX661 and VX445. view this paper - Issues are regarded as officially published after their release is announced to the table of contents alert mailing list .
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