In Silico Toxicology
Predicting drug-induced arrhythmias (Torsades de Pointes) via hERG channel blockade simulation.
Target Channel
hERG (Kv11.1)
Potassium Repolarization Current
IC50 Value
10.0 nM
Half-maximal inhibitory conc.
Safety Margin
5.0x
Therapeutic Index (TI)
TdP Risk
HIGH
At >50nM concentration
Dose-Response Curve (APD90)
Action Potential Duration vs. Drug Concentration. Note the sharp rise (QT Prolongation) starting at 20nM.
Mechanism of Action
hERG Blockade
The drug binds to the inner pore of the hERG channel, preventing K+ efflux.
Repolarization Delay
Without K+ exit, the cell stays positive longer (Plateau Phase extends).
EAD Formation
Calcium channels reactivate during the long plateau, causing "Early Afterdepolarizations" → Torsades.
Safety Warning
This compound shows significant QT prolongation at 5x therapeutic dose. Recommendation: DO NOT PROCEED to Phase 1 Human Trials without structural modification.