Advancing Torsades de pointes risk prediction: unveiling the role of drug metabolites through molecular docking.

ABSTRACT: This study explores the risk of Torsades de Pointes (TdP) arrhythmia, focusing on the interactions of parent drugs and their metabolites with the Human ether-à-go-go-related gene (hERG) channel, which is crucial in cardiac electrical activity and TdP risk assessment. Using a dual-strategy molecular docking approach with AutoDock Vina and PatchDock, we analyzed clinically relevant ligand pairs: astemizole/desmethylastemizole, terfenadine/fexofenadine, and quetiapine/norquetiapine. Quantitative analysis revealed that high binding affinity does not always correlate with toxicity. For instance, the non-cardiotoxic metabolite fexofenadine exhibited a higher binding affinity (-9.3 kcal/mol) compared to its toxic parent terfenadine (-8.9 kcal/mol), but its safety is explained by physicochemical c

SUBMITTER: Bilgin E 

PROVIDER: S-EPMC12853304 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature