Referenced in: none

Automatically associated channels: Kv11.1

Title: A virtual screening method for prediction of the HERG potassium channel liability of compound libraries.

Authors: Olivier Roche, Gerhard Trube, Jochen Zuegge, Pascal Pflimlin, Alexander Alanine, Gisbert Schneider

Journal, date & volume: Chembiochem, 2002 May 3 , 3, 455-9

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/12007180

Abstract
A computer-based method has been developed for prediction of the hERG (human ether-à-go-go related gene) K(+)-channel affinity of low molecular weight compounds. hERG channel blockage is a major concern in drug design, as such blocking agents can cause sudden cardiac death. Various techniques were applied to finding appropriate molecular descriptors for modeling structure-activity relationships: substructure analysis, self-organizing maps (SOM), principal component analysis (PCA), partial least squares fitting (PLS), and supervised neural networks. The most accurate prediction system was based on an artificial neural network. In a validation study, 93 % of the nonblocking agents and 71 % of the hERG channel blockers were correctly classified. This virtual screening method can be used for general compound-library shaping and combinatorial library design.