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High-throughput Screening for Small-molecule Modulators of Inward Rectifier Potassium Channels
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The hERG K+ channel: target and antitarget strategies in drug development

Emanuel Raschi1, Valentina Vasina, Elisabetta Poluzzi

  • 1Department of Pharmacology, University of Bologna, Via Irnerio, 48, I-40126 Bologna BO, Bologna, Italy.

Pharmacological Research
|March 11, 2008
PubMed

Insights

Drug blockade of the human ether-à-go-go related gene (hERG) K+ channel causes QT prolongation and arrhythmias. hERG channels in other tissues may offer new therapeutic targets in oncology and cardiology.

Area of Science:

  • Pharmacology
  • Cardiology
  • Molecular Biology

Background:

  • The human ether-à-go-go related gene (hERG) K+ channel is crucial for cardiac repolarization.
  • Drug-induced blockade of hERG channels can cause QT prolongation and torsades de pointes, a life-threatening arrhythmia.
  • Several drugs have been withdrawn or restricted due to hERG channel liabilities, highlighting its role as an antitarget in drug development.

Purpose of the Study:

  • To review the significance of hERG K+ channels in drug safety and development.
  • To explore the emerging roles of hERG channels in non-cardiac tissues.
  • To discuss the potential of hERG channels as therapeutic targets, particularly in oncology and cardiology.

Main Methods:

  • Literature review of studies on hERG channel function, drug interactions, and tissue distribution.
  • Analysis of the implications of hERG channel blockade for drug safety.
  • Evaluation of recent findings on hERG channel expression and function in various tissues.

Main Results:

  • hERG channel blockade is a major cause of drug-induced cardiotoxicity.
  • A significant number of drugs have faced regulatory actions due to hERG liability.
  • hERG channels are expressed in diverse tissues, including neurons, smooth muscle, and cancer cells, suggesting broader physiological roles.

Conclusions:

  • hERG K+ channels represent a critical safety concern in drug development, acting as a primary antitarget.
  • The presence and function of hERG channels in non-cardiac tissues open new avenues for therapeutic intervention.
  • Targeting hERG channels may offer novel strategies for treating conditions in oncology and cardiology.

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