A discriminant model constructed by the support vector machine method for HERG potassium channel inhibitors.

Article Details

Citation

Tobita M, Nishikawa T, Nagashima R

A discriminant model constructed by the support vector machine method for HERG potassium channel inhibitors.

Bioorg Med Chem Lett. 2005 Jun 2;15(11):2886-90.

PubMed ID
15911273 [ View in PubMed
]
Abstract

HERG attracts attention as a risk factor for arrhythmia, which might trigger torsade de pointes. A highly accurate classifier of chemical compounds for inhibition of the HERG potassium channel is constructed using support vector machine. For two test sets, our discriminant models achieved 90% and 95% accuracy, respectively. The classifier is even applied for the prediction of cardio vascular adverse effects to achieve about 70% accuracy. While modest inhibitors are partly characterized by properties linked to global structure of a molecule including hydrophobicity and diameter, strong inhibitors are exclusively characterized by properties linked to substructures of a molecule.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
AmiodaroneHERG human cardiac K+ channelIC 50 (nM)10000N/AN/ADetails
AstemizolePotassium voltage-gated channel subfamily H member 2IC 50 (nM)10N/AN/ADetails
AzimilidePotassium voltage-gated channel subfamily H member 2IC 50 (nM)1412.54N/AN/ADetails
BepridilPotassium voltage-gated channel subfamily H member 2IC 50 (nM)549.54N/AN/ADetails
CarvedilolPotassium voltage-gated channel subfamily H member 2IC 50 (nM)10471.29N/AN/ADetails
ChlorpromazinePotassium voltage-gated channel subfamily H member 2IC 50 (nM)1479.11N/AN/ADetails
CisapridePotassium voltage-gated channel subfamily H member 2IC 50 (nM)39.81N/AN/ADetails
ClarithromycinPotassium voltage-gated channel subfamily H member 2IC 50 (nM)58884.37N/AN/ADetails
DisopyramidePotassium voltage-gated channel subfamily H member 2IC 50 (nM)91201.08N/AN/ADetails
DofetilidePotassium voltage-gated channel subfamily H member 2IC 50 (nM)10N/AN/ADetails
FlecainidePotassium voltage-gated channel subfamily H member 2IC 50 (nM)3890.45N/AN/ADetails
FluoxetinePotassium voltage-gated channel subfamily H member 2IC 50 (nM)1513.56N/AN/ADetails
HalofantrinePotassium voltage-gated channel subfamily H member 2IC 50 (nM)200N/AN/ADetails
IbutilidePotassium voltage-gated channel subfamily H member 2IC 50 (nM)10N/AN/ADetails
ImipraminePotassium voltage-gated channel subfamily H member 2IC 50 (nM)3388.44N/AN/ADetails
LoratadinePotassium voltage-gated channel subfamily H member 2IC 50 (nM)169.82N/AN/ADetails
PimozidePotassium voltage-gated channel subfamily H member 2IC 50 (nM)50.12N/AN/ADetails
PrazosinPotassium voltage-gated channel subfamily H member 2IC 50 (nM)1584.89N/AN/ADetails
ProcainamidePotassium voltage-gated channel subfamily H member 2IC 50 (nM)138038.43N/AN/ADetails
SertindolePotassium voltage-gated channel subfamily H member 2IC 50 (nM)10N/AN/ADetails
TerfenadinePotassium voltage-gated channel subfamily H member 2IC 50 (nM)200N/AN/ADetails
ThioridazinePotassium voltage-gated channel subfamily H member 2IC 50 (nM)190.55N/AN/ADetails