Prediction of hERG Channel Inhibition Using In Silico Techniques - Ion Channels and Their Inhibitors - page 192

inhibitory activity of hits and lead compounds thus is of major importance in the
drug discovery and development process. Both structure- and ligand-based
approaches were used to develop models, which shed light on the molecular basis
of hERG channel inhibition. In this article, an overview on recent approaches for
prediction of hERG channel blockers has been provided.

Keywords hERG • Pharmacophore • QSAR • Classification • Homology
model • Docking

Abbreviations

ADMET Absorption, distribution, metabolism, elimination and toxicity

AUC Area under the curve

CCR Chemokine receptor

CoMFA Comparative molecular field analysis

CoMSIA Comparative molecular similarity indices analysis

CPG-NN Counter-propagation neural network

CSD Cambridge structural database

eag Ether-a-go-go

ECG Electrocardiogram

Human ether-a-go-go-related-gene K þ channel

hERG

ISA Iterative simulated annealing

KNN k Nearest neighbor

LDA Linear discriminant analysis

LIE Linear interaction energy

LMS Least median squares

LQTs Long QT syndrome

LSER Linear solvation energy relationship

MD Molecular dynamics

PCA Principal component analysis

PLS Partial least squares

PLS-DA Partial least squares discriminant analysis

PNN Probabilistic neural network

QA Quaternary ammonium

QSAR Quantitative structure-activity relationship

RF Random forest

ROC Receiver operating characteristic

S Transmembrane domain

SA Simulated annealing

SAR Structure-activity relationship

SOM Self-organizing maps

SVM Support vector machine

SVR Support vector regression

TdP Torsade de Pointes