In silico prediction of hERG inhibition.
The voltage-gated potassium channel encoded by hERG carries a delayed rectifying potassium current (IKr) underlying repolarization of the cardiac action potential. Pharmacological blockade of the hERG channel results in slowed repolarization and therefore prolongation of action potential duration and an increase in the QT interval as measured on an electrocardiogram. Those are possible to cause sudden death, leading to the withdrawals of many drugs, which is the reason for hERG screening. Computational in silico prediction models provide a rapid, economic way to screen compounds during early drug discovery. In this review, hERG prediction models are classified as 2D and 3D quantitative structure-activity relationship models, pharmacophore models, classification models, and structure based models (using homology models of hERG).
Biogen Idec, 250 Binney Street, Cambridge, MA 02142, USA.
Yankang
Y
Jing
Alison
A
Easter
David
D
Peters
Norman
N
Kim
Istvan J
IJ
Enyedy
D003198:Computer Simulation; D017076:Computer-Aided Design; D055808:Drug Discovery / Q000379:methods*; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D026902:Potassium Channel Blockers / Q000737:chemistry* / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship
D051638:Ether-A-Go-Go Potassium Channels; D026902:Potassium Channel Blockers