A binary QSAR model for classification of hERG potassium channel blockers

Bioorganic & Medicinal Chemistry
2008.0

Abstract

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.

Knowledge Graph

Similar Paper

A binary QSAR model for classification of hERG potassium channel blockers
Bioorganic & Medicinal Chemistry 2008.0
Prediction of hERG potassium channel affinity by traditional and hologram qSAR methods
Bioorganic & Medicinal Chemistry Letters 2003.0
Toward a Pharmacophore for Drugs Inducing the Long QT Syndrome:  Insights from a CoMFA Study of HERG K<sup>+</sup> Channel Blockers
Journal of Medicinal Chemistry 2002.0
Support vector machines classification of hERG liabilities based on atom types
Bioorganic &amp; Medicinal Chemistry 2008.0
A discriminant model constructed by the support vector machine method for HERG potassium channel inhibitors
Bioorganic &amp; Medicinal Chemistry Letters 2005.0
Development, Validation, and Use of Quantitative Structure−Activity Relationship Models of 5-Hydroxytryptamine (2B) Receptor Ligands to Identify Novel Receptor Binders and Putative Valvulopathic Compounds among Common Drugs
Journal of Medicinal Chemistry 2010.0
Predicting hERG activities of compounds from their 3D structures: Development and evaluation of a global descriptors based QSAR model
European Journal of Medicinal Chemistry 2011.0
Predictive model for L‐type channel inhibition: multichannel block in QT prolongation risk assessment
Journal of Applied Toxicology 2012.0
Identification of “toxicophoric” features for predicting drug-induced QT interval prolongation
European Journal of Medicinal Chemistry 2008.0
Simulation of multiple ion channel block provides improved early prediction of compounds’ clinical torsadogenic risk
Cardiovascular Research 2011.0