Prediction of hERG potassium channel affinity by traditional and hologram qSAR methods.

Article Details

Citation

Keseru GM

Prediction of hERG potassium channel affinity by traditional and hologram qSAR methods.

Bioorg Med Chem Lett. 2003 Aug 18;13(16):2773-5.

PubMed ID
12873512 [ View in PubMed
]
Abstract

Traditional and hologram QSAR (HQSAR) models were developed for the prediction of hERG potassium channel affinities. The models were validated on three different test sets including compounds with published patch-clamp IC(50) data and two subsets from the World Drug Index (compounds indicated to have ECG modifying adverse effect and drugs marked to be approved, respectively). Discriminant analysis performed on the full set of hERG data resulted in a traditional QSAR model that classified 83% of actives and 87% of inactives correctly. Analysis of our HQSAR model revealed it to be predictive in both IC(50) and discrimination studies.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
CiprofloxacinPotassium voltage-gated channel subfamily H member 2ProteinHumans
Unknown
Not AvailableDetails
ClarithromycinPotassium voltage-gated channel subfamily H member 2ProteinHumans
Unknown
Not AvailableDetails
Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
AmiodaroneHERG human cardiac K+ channelIC 50 (nM)10000N/AN/ADetails
AstemizolePotassium voltage-gated channel subfamily H member 2IC 50 (nM)6N/AN/ADetails
AzimilidePotassium voltage-gated channel subfamily H member 2IC 50 (nM)1413N/AN/ADetails
BepridilPotassium voltage-gated channel subfamily H member 2IC 50 (nM)550N/AN/ADetails
CarvedilolPotassium voltage-gated channel subfamily H member 2IC 50 (nM)10471N/AN/ADetails
ChlorpromazinePotassium voltage-gated channel subfamily H member 2IC 50 (nM)1479N/AN/ADetails
CisapridePotassium voltage-gated channel subfamily H member 2IC 50 (nM)40N/AN/ADetails
ClarithromycinPotassium voltage-gated channel subfamily H member 2IC 50 (nM)58884.37N/AN/ADetails
ClarithromycinPotassium voltage-gated channel subfamily H member 2IC 50 (nM)33113.11N/AN/ADetails
DisopyramidePotassium voltage-gated channel subfamily H member 2IC 50 (nM)91201N/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)3890N/AN/ADetails
FluoxetinePotassium voltage-gated channel subfamily H member 2IC 50 (nM)1514N/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)3388N/AN/ADetails
LoratadinePotassium voltage-gated channel subfamily H member 2IC 50 (nM)170N/AN/ADetails
PerhexilinePotassium voltage-gated channel subfamily H member 2IC 50 (nM)7762N/AN/ADetails
PimozidePotassium voltage-gated channel subfamily H member 2IC 50 (nM)50N/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)363N/AN/ADetails