Novel indole and benzothiophene ring derivatives showing differential modulatory activity against human epithelial sodium channel subunits, ENaC β and γ

Yoichi Kasahara, Takanobu Sakurai, Ryusei Matsuda, Masataka Narukawa, Akihito Yasuoka, Naoki Mori, Hidenori Watanabe, Takayoshi Okabe, Hirotatsu Kojima, Keiko Abe, Takumi Misaka, Tomiko Asakura

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)243-250
Number of pages8
JournalBioscience, Biotechnology and Biochemistry
Volume83
Issue number2
DOIs
Publication statusPublished - 2019
Externally publishedYes

Keywords

  • Chemical library
  • ENaC (epithelial sodium channel)
  • Sodium channel

ASJC Scopus subject areas

  • Biotechnology
  • Analytical Chemistry
  • Biochemistry
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Organic Chemistry

Fingerprint Dive into the research topics of 'Novel indole and benzothiophene ring derivatives showing differential modulatory activity against human epithelial sodium channel subunits, ENaC β and γ'. Together they form a unique fingerprint.

Cite this