A binary QSAR model for classification of hERG potassium channel blockers.
Acquired long QT syndrome causes severe cardiac side effects and represents a major problem in clinical studies of drug candidates. One of the reasons for development of arrhythmias related to long QT is inhibition of the human ether-a-go-go-related-gene (hERG) potassium channel. Therefore, early prediction of hERG K(+) channel affinity of drug candidates is becoming increasingly important in the drug discovery process. Binary QSAR models with threshold values at IC(50)=1 and of 10 microM, respectively, were generated using two different sets of descriptors. One set comprising 32 P_VSA descriptors and the other one utilizing a set of descriptors identified out of a large set via a feature selection algorithm. For the full dataset, the power for classification of hERG blockers was 82-88%, which meets prior classification models. Considering the fact that 2D descriptors are fast and easy to calculate, these binary QSAR models are versatile tools for use in virtual screening protocols.
Thai
Khac-Minh
KM
Emerging Field Pharmacoinformatics, Department of Medicinal Chemistry, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria.
Ecker
Gerhard F
GF
D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D015394:Molecular Structure; D026902:Potassium Channel Blockers / Q000737:chemistry* / Q000145:classification / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship
D051638:Ether-A-Go-Go Potassium Channels; D026902:Potassium Channel Blockers