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- W2896815913 abstract "ABSTRACT The epithelial sodium channel (ENaC) plays a pivotal role in sodium homeostasis, and the development of drugs that modulate ENaC activity is of great potential therapeutic relevance. We screened 6100 chemicals for their ability to activate sodium permeability of ENaC. We used a two-step strategy: a high throughput cell-based assay and an electrophysiological assay. Five compounds were identified showing common structural features including an indole or benzothiophene ring. ENaC consists of three subunits: α, β, and γ. Changing the heteromeric combination of human and mouse ENaC αβγ subunits, we found that all five compounds activated the human β subunit but not the mouse subunit. However, four of them exhibited lower activity when the human γ subunit was substituted by the mouse γ subunit. Our findings provide a structural basis for designing human ENaC activity modulators. Abbreviations: ENaC: Epithelial sodium channel; ΔRFU: delta relative fluorescence units; EC50: Half-maximal effective concentration; Emax: maximum effect value." @default.
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- W2896815913 date "2019-02-01" @default.
- W2896815913 modified "2023-10-03" @default.
- W2896815913 title "Novel indole and benzothiophene ring derivatives showing differential modulatory activity against human epithelial sodium channel subunits, ENaC β and γ" @default.
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- W2896815913 doi "https://doi.org/10.1080/09168451.2018.1533802" @default.
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