Natural products modulating the hERG channel: heartaches and hope

Natural Product Reports
Jadel M KratzJudith M Rollinger

Abstract

Covering: 1996-December 2016The human Ether-à-go-go Related Gene (hERG) channel is a voltage-gated potassium channel playing an essential role in the normal electrical activity in the heart. It is involved in the repolarization and termination of action potentials in excitable cardiac cells. Mutations in the hERG gene and hERG channel blockage by small molecules are associated with increased risk of fatal arrhythmias. Several drugs have been withdrawn from the market due to hERG channel-related cardiotoxicity. Moreover, as a result of its notorious ligand promiscuity, this ion channel has emerged as an important antitarget in early drug discovery and development. Surprisingly, the hERG channel blocking profile of natural compounds present in frequently consumed botanicals (i.e. dietary supplements, spices, and herbal medicinal products) is not routinely assessed. This comprehensive review will address these issues and provide a critical compilation of hERG channel data for isolated natural products and extracts over the past two decades (1996-2016). In addition, the review will provide (i) a solid basis for the molecular understanding of the physiological functions of the hERG channel, (ii) the translational potential of in vit...Continue Reading

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Citations

Feb 17, 2019·Journal of Cellular Physiology·Habib HaybarNajmaldin Saki
Sep 25, 2019·Cold Spring Harbor Perspectives in Biology·Jacinta Isabelle Kalisch-SmithDuncan Burnaby Sparrow
Sep 4, 2019·PloS One·Bryan CernudaZafir Buraei
Jul 30, 2020·Molecular Informatics·Ya Chen, Johannes Kirchmair
Apr 14, 2020·European Journal of Medicinal Chemistry·Amanda GarridoChristophe Rochais
Mar 18, 2021·European Journal of Pharmacology·Simona SaponaraMassimo Valoti

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Methods Mentioned

BETA
in silico methods
fluorescence resonance
FRET
chip

Software Mentioned

hERG
ChemGPS
Pred
CiPA

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