Insights for Human Ether-a-Go-Go-Related Gene Potassium Channel Inhibition Using Recursive Partitioning and Kohonen and Sammon Mapping Techniques, J. Med. Chem. 2006, 49(17), 5059-5071.
We have collated literature data for 99 diverse hERG inhibitors to generate Kohonen maps, Sammon maps, and recursive partitioning models. Our aim was to investigate whether these computational models could be used either individually or together in a consensus approach to predict the binding of a prospectively selected test set of 35 diverse molecules and at the same time to offer further insights into hERG inhibition. The recursive partitioning model provided a quantitative prediction, which was markedly improved when Tanimoto similarity was included as a filter to remove molecules from the test set that were too dissimilar to the training set (r2 = 0.83, Spearman rho = 0.75, p = 0.0003 for the 18 remaining molecules, >0.77 similarity).The datasets can be downloaded from the WSAR world pages: http://www.qsarworld.com/qsar-datasets-ekins.php