Key result
CJ-033466 demonstrated lower hERG-blocking potency (IC50 2.6 x 10^-6 M) than cisapride (IC50 9.4 x 10^-9 M), suggesting a wider safety margin for cardiac arrhythmia risk.
The novel 5-HT4 agonist CJ-033466 demonstrates a wider safety margin for hERG channel blockade compared to cisapride and mosapride, suggesting a lower risk of drug-induced arrhythmias.
May prioritize 5-HT4 agonists with wider hERG margins in development; leaves open clinical arrhythmia risk confirmation.
The blocking effect of three 5-HT(4) agonists, cisapride, mosapride, and the newly discovered CJ-033466 on the human ether-a-go-go-related gene (hERG) channel was studied using a whole cell patch-clamp technique in HEK293 cells. Cisapride was found to be the most potent of the hERG blockers. CJ-033466 had the widest safety margin between its hERG blocking activity and 5-HT(4) agonism among the tested compounds. This suggests a lower clinical risk of cardiac arrhythmia in CJ-033466 compared with the other 2 agonists. Therefore, CJ-033466 has the potential to be a drug with higher therapeutic efficacy and less cardiac risk than both cisapride and mosapride.
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Toga et al. (2007) studied hERG channel blocking (cardiac safety) (n=45). CJ-033466 vs. Cisapride and Mosapride was evaluated on hERG channel blocking activity (IC50). CJ-033466 demonstrated lower hERG-blocking potency (IC50 2.6 x 10^-6 M) than cisapride (IC50 9.4 x 10^-9 M), suggesting a wider safety margin for cardiac arrhythmia risk.
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