Biochem/physiol Actions

LUF7346 is a Kv11.1 (hERG) allosteric modulator that prevents proarrhythmic effects caused by hERG blockers in rat ventricular myocyte cultures. LUF7346 reduces Kv11.1 (ERG) affinity toward known Kv11.1 channel blockers dofetilide (Ki for hERG = 4.8 nM without and 12 nM with 10 µM LUF7346) and astemizole (Ki for for hERG = 1.3 nM without and 5.3 nM with 10 µM LUF7346) and effectively suppresses astemizole-induced arrhythmogenic events in a dose-dependent manner among Long-QT syndrome/LQTS (LQT1, JLNS, LQT2) and control isogenic human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). LUF7346 is shown to slow IKr deactivation and positively shifts IKr inactivation among LQTS and control isogenic hiPSC-CMs without affecting KCNQ1/KCNE1-dependent IKs or L-type calcium current ICaL.

LUF7346 has the ability to enhance the potassium current (IKr) in a heterologous system. It is found to be highly effective than other human ether-a-go-go-related gene (hERG) activators, such as Rottlerin and NS1643.

Packaging

5, 25 mg in glass bottle