Predictive in silico modeling for hERG channel blockers.
hERG-mediated sudden death as a side effect of non-antiarrhythmic drugs has been receiving increased regulatory attention. Perhaps owing to the unique shape of the ligand-binding site and its hydrophobic character, the hERG channel has been shown to interact with pharmaceuticals of widely varying structure. Several in silico approaches have attempted to predict hERG channel blockade. Some of these approaches are aimed primarily at filtering out potential hERG blockers in the context of virtual libraries, others involve understanding structure-activity relationships governing hERG-drug interactions. This review summarizes the most recent efforts in this emerging field.
Aronov
Alex M
AM
Vertex Pharmaceuticals Inc., 130 Waverly St., Cambridge, MA 02139-4242, USA. alex_aronov@vrtx.com
D027682:Cation Transport Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D003645:Death, Sudden / Q000209:etiology; D064420:Drug-Related Side Effects and Adverse Reactions; D051638:Ether-A-Go-Go Potassium Channels; D006801:Humans; D008958:Models, Molecular; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000145:classification; D026902:Potassium Channel Blockers / Q000737:chemistry* / Q000145:classification; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship
D027682:Cation Transport Proteins; D051638:Ether-A-Go-Go Potassium Channels; C092509:KCNH6 protein, human; D004364:Pharmaceutical Preparations; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated