Key result
Hirsutenone directly blocked hERG K+ channels in a concentration-dependent manner with an IC50 of 14.9 μM by modifying channel inactivation kinetics.
Why the study?
Does hirsutenone block hERG K+ channels and alter their kinetics in hERG-expressing CHO cells?
Does hirsutenone block hERG K+ channels and alter their kinetics in hERG-expressing CHO cells?
Effect estimate: IC50 14.9 μM
p-value: p=<0.01
Hirsutenone acts as a direct blocker of hERG K+ channels by modifying inactivation kinetics, suggesting a potential risk for drug-induced long QT syndrome if administered systemically.
The aim of the present study was to investigate whether hirsutenone affects the human ether-a-go-go related gene (hERG) K(+) channels. Many drugs promote formation of the acquired form of long QT syndrome (LQTS) by blocking the hERG K(+) channels. Hirsutenone, a new candidate for the treatment inflammatory skin lesions, induced a concentration-dependent decrease in hERG K(+) current amplitudes. Hirsutenone significantly decreased the time constants at the onset of inactivation. However, the reductions in the time constants of steady-state inactivation and the recovery from inactivation after hirsutenone treatment were not significant. In addition, the drug had no effect on the voltage-dependent activation curve or the steady-state inactivation curve. In summary, hirsutenone potentially acts as a blocker of hERG K(+) channels functioning by modifying the channel inactivation kinetics.
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Yun et al. (2011) studied Drug-induced Long QT Syndrome potential. Hirsutenone vs. Control (untreated/vehicle) was evaluated on hERG K+ current amplitude (Itail) (IC50 14.9 μM, p=<0.01). Hirsutenone directly blocked hERG K+ channels in a concentration-dependent manner with an IC50 of 14.9 μM by modifying channel inactivation kinetics.
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