The hERG potassium channel and drug trapping: insights from docking studies with propafenone derivatives
- Author(s)
- Khac Minh Thai, Andreas Windisch, Daniela Stork, Anna Weinzinger, Andrea Schiesaro, H. Robert Guy, Evgeny Timin, Steffen Hering, Gerhard Ecker
- Abstract
The inner cavity of the hERG potassium ion channel can accommodate large, structurally diverse compounds that can be trapped in the channel by closure of the activation gate. A small set of propafenone derivatives was synthesized, and both use-dependency and recovery from block were tested in order to gain insight into the behavior of these compounds with respect to trapping and non-trapping. Ligand-protein docking into homology models of the closed and open state of the hERG channel provides the first evidence for the molecular basis of drug trapping.
- Organisation(s)
- External organisation(s)
- National Institutes of Health (NIH)
- Journal
- ChemMedChem: chemistry enabling drug discovery
- Volume
- 5
- Pages
- 436-442
- No. of pages
- 7
- ISSN
- 1860-7179
- DOI
- https://doi.org/10.1002/cmdc.200900374
- Publication date
- 2010
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 301206 Pharmacology, 106005 Bioinformatics
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/1e8788fa-275b-454f-97b3-b1cfc6519936