Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Molecular Pharmacology
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Molecular Pharmacology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

Biophysical Characterization of the New Human Ether-A-Go-Go-Related Gene Channel Opener NS3623 [N-(4-Bromo-2-(1H-tetrazol-5-yl)-phenyl)-N′-(3′-trifluoromethylphenyl)urea]

Rie Schultz Hansen, Thomas Goldin Diness, Torsten Christ, Erich Wettwer, Ursula Ravens, Søren-Peter Olesen and Morten Grunnet
Molecular Pharmacology October 2006, 70 (4) 1319-1329; DOI: https://doi.org/10.1124/mol.106.026492
Rie Schultz Hansen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thomas Goldin Diness
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Torsten Christ
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Erich Wettwer
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ursula Ravens
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Søren-Peter Olesen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Morten Grunnet
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

Within the field of new antiarrhythmic compounds, the interesting idea of activating human ether-a-go-go-related gene (HERG1) potassium channels has recently been introduced. Potentially, drugs that increase HERG1 channel activity will augment the repolarizing current of the cardiac myocytes and stabilize the diastolic interval. This may make the myocardium more resistant to events that cause arrhythmias. We here present the compound N-(4-bromo-2-(1H-tetrazol-5-yl)-phenyl)-N′-(3′-trifluoromethylphenyl)urea (NS3623), which has the ability to activate HERG1 channels expressed in Xenopus laevis oocytes with an EC50 value of 79.4 μM. Exposure of HERG1 channels to NS3623 affects the voltage-dependent release from inactivation, resulting in a half-inactivation voltage that is rightward-shifted by 17.7 mV. Moreover, the compound affects the time constant of inactivation, leading to a slower onset of inactivation of the macroscopic HERG1 currents. We also characterized the ability of NS3623 to increase the activity of different mutated HERG1 channels. The mutants S620T and S631A are severely compromised in their ability to inactivate. Application of NS3623 to any of these two mutants did not result in increased HERG1 current. In contrast, application of NS3623 to the mutant F656M increased HERG1 current to a larger extent than what was observed with wild-type HERG1 channels. Because the amino acid F656 is essential for high-affinity inhibition of HERG1 channels, it is concluded that NS3623 has a dual mode of action, being both an activator and an inhibitor of HERG1 channels. Finally, we show that NS3623 has the ability to shorten action potential durations in guinea pig papillary muscle.

Footnotes

  • This work was supported by the Danish National Research Foundation Center for Cardiac Arrhythmia.

  • ABBREVIATIONS: HERG, human ether-a-go-go-related gene; APD, action potential duration; NS1643, 1,3-bis-(2-hydroxy-5-trifluoromethylphenyl)-urea; NS3623, N-(4-bromo-2-(1H-tetrazol-5-yl)-phenyl)-N′-(3′-trifluoromethylphenyl)urea; HEK, human embryonic kidney.

    • Received May 16, 2006.
    • Accepted July 5, 2006.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Molecular Pharmacology: 70 (4)
Molecular Pharmacology
Vol. 70, Issue 4
1 Oct 2006
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Pharmacology article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Biophysical Characterization of the New Human Ether-A-Go-Go-Related Gene Channel Opener NS3623 [N-(4-Bromo-2-(1H-tetrazol-5-yl)-phenyl)-N′-(3′-trifluoromethylphenyl)urea]
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Biophysical Characterization of the New Human Ether-A-Go-Go-Related Gene Channel Opener NS3623 [N-(4-Bromo-2-(1H-tetrazol-5-yl)-phenyl)-N′-(3′-trifluoromethylphenyl)urea]

Rie Schultz Hansen, Thomas Goldin Diness, Torsten Christ, Erich Wettwer, Ursula Ravens, Søren-Peter Olesen and Morten Grunnet
Molecular Pharmacology October 1, 2006, 70 (4) 1319-1329; DOI: https://doi.org/10.1124/mol.106.026492

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleArticle

Biophysical Characterization of the New Human Ether-A-Go-Go-Related Gene Channel Opener NS3623 [N-(4-Bromo-2-(1H-tetrazol-5-yl)-phenyl)-N′-(3′-trifluoromethylphenyl)urea]

Rie Schultz Hansen, Thomas Goldin Diness, Torsten Christ, Erich Wettwer, Ursula Ravens, Søren-Peter Olesen and Morten Grunnet
Molecular Pharmacology October 1, 2006, 70 (4) 1319-1329; DOI: https://doi.org/10.1124/mol.106.026492
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Mechanism of the selective action of paraherquamide A
  • Use-Dependent Relief of A-887826 Inhibition
  • Benzbromarone Relaxes Airway Smooth Muscle via BK Activation
Show more Articles

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About Molecular Pharmacology
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics