Scholarlink

<p>Na<sub>v</sub>1.5 is the main sodium channel subtype in the heart, playing a crucial role in maintaining regular cardiac electrical activity. It is a well-established therapeutic target for class I antiarrhythmic drugs used to treat both inherited and acquired arrhythmias. In this study, we report a highly effective (IC<sub>50</sub> = 1.38 ± 0.28 μM) and novel Na<sub>v</sub>1.5 inhibitor, KH2, identified through an integrated drug discovery approach. Molecular dynamics (MD) simulations and experimental findings reveal that, unlike traditional class I antiarrhythmic drugs, KH2 shows a completely novel binding mechanism. Moreover, using electrophysiological mapping systems on rat isolated hearts, we found that KH2 significantly reduced cardiac conduction, highlighting its potential as a therapeutic agent for arrhythmias. Our finding of KH2 provided a valuable reference for designing drugs targeting Na<sub>v</sub>1.5 to treat arrhythmias.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Discovery of a novel Nav1.5 inhibitor reducing cardiac conduction via structure-based virtual screening and assays

  • 期刊论文

  • 发表日期：

    2026年1月1日

查看全文
  • Ying-ying Wang,
  • Gao-ang Wang,
  • Qing You,
  • Yi-fei Liu,
  • Wang-lin Qu,
  • Yi-hong Chen,
  • Chen-zhang Mu,
  • Xi Zhou,
  • Min Liu,
  • Wei Yang,
  • Ting-jun Hou

摘要

Nav1.5 is the main sodium channel subtype in the heart, playing a crucial role in maintaining regular cardiac electrical activity. It is a well-established therapeutic target for class I antiarrhythmic drugs used to treat both inherited and acquired arrhythmias. In this study, we report a highly effective (IC50 = 1.38 ± 0.28 μM) and novel Nav1.5 inhibitor, KH2, identified through an integrated drug discovery approach. Molecular dynamics (MD) simulations and experimental findings reveal that, unlike traditional class I antiarrhythmic drugs, KH2 shows a completely novel binding mechanism. Moreover, using electrophysiological mapping systems on rat isolated hearts, we found that KH2 significantly reduced cardiac conduction, highlighting its potential as a therapeutic agent for arrhythmias. Our finding of KH2 provided a valuable reference for designing drugs targeting Nav1.5 to treat arrhythmias.