Nonlinear classification of hERG channel inhibitory activity by unsupervised classification method.
The side effects that occur in the central nervous system and circulatory system due to medicines are expected to be prevented by research and development. However, many of the compounds in medicines have the possibility of causing arrhythmia, and methods developed to detect this problem at the early stage of drug development are not always successful. In the present study, we classified drug compounds according to their activity using only structural information. To classify compounds, we used a self-organizing map (SOM), which is a nonlinear unsupervised classification method. We first analyzed a small-scale dataset, and an excellent classification result was obtained. We then applied our method to a large-scale dataset containing numerous inert compounds and were again able to classify the compounds according to their activity. Both classifications showed some compound activity, although a few differences between the two SOM maps were seen.
Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka, Suita, Osaka, Japan. ttakagi@phs.osaka-u.ac.jp
Shinnosuke
S
Hidaka
Hiroyuki
H
Yamasaki
Yoshihiro
Y
Ohmayu
Akiko
A
Matsuura
Kousuke
K
Okamoto
Norihito
N
Kawashita
Tatsuya
T
Takagi
D000818:Animals; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors*; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced; D015201:Meta-Analysis as Topic; D008722:Methods; D008958:Models, Molecular; D004364:Pharmaceutical Preparations / Q000145:classification*; D021281:Quantitative Structure-Activity Relationship
D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D004364:Pharmaceutical Preparations