Referenced in: none

Automatically associated channels: Kv11.1

Title: Are hERG channel blockers also phospholipidosis inducers?

Authors: Hongmao Sun, Menghang Xia, Sampada A Shahane, Ajit Jadhav, Christopher P Austin, Ruili Huang

Journal, date & volume: Bioorg. Med. Chem. Lett., 2013 Aug 15 , 23, 4587-90

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23856051

Abstract
Both pharmacophore models of the human ether-à-go-go-related gene (hERG) channel blockers and phospholipidosis (PLD) inducers contain a hydrophobic moiety and a hydrophilic motif/positively charged center, so it is interesting to investigate the overlap between the ligand chemical spaces of both targets. We have assayed over 4000 non-redundant drug-like compounds for both their hERG inhibitory activity and PLD inducing potential in a quantitative high throughput screening (qHTS) format. Seventy-seven percent of PLD inducing compounds identified from the screening were also found to be hERG channel blockers, and 96.9% of the dually active compounds were positively charged. Among the 48 compounds that induced PLD without inhibiting hERG channel, 24 compounds (50.0%) carried steroidal structures. According to our results, hERG channel blockers and PLD inducers share a large chemical space. In addition, a positively charged hERG channel blocker will most likely induce PLD, while a steroid PLD inducer is less likely a hERG channel blocker.