CaMKII (Ca2+/calmodulin-dependent protein kinase II), a multi functional protein kinase, is ubiquitously involved in many physiological processes including control of cell cycle, apoptosis, gene expression, and neurotransmission. KN-93, as a membrane permeant compound of CaMKII-selective inhibitor, can intensively prevent CaMK-II activation by antagonizing CaM binding. In contrast to KN-93, KN-92 is a congener of KN-93 without CaM kinase inhibitory activity and has been used as an experimental control. KN-93 inhibited proliferation of LX-2 cells in a dose- and time-dependent manner, but KN-92 was ineffective in blocking cell growth. KN-92 showed little impact on p53 expression, demonstrating that it was KN-93 rather than KN-92 increased p53 expression in a dose-dependent manner[3]. The incidence of EADs (early after-depolarizations) and I(Ca, L) in the hypertrophic cardiomyocytes were evaluated after treatment with different concentrations of KN-92. The incidence of EADs was 10/12 in KN-92 group (0.5 μmol/L). When the drug concentration was increased to 1 μmol/L in KN-92 group, the incidence of EADs remained the same. When the drug concentration was 0.5 μmol/L in KN-92 groups, the peak I(Ca, L) at 0 mV was decreased by (9.4 ± 2.8)% in the hypertrophic cardiomyocytes (P>0.05, n=12). When the drug concentration was increased to 1 μmol/L, the peak I(Ca, L) value was lowered by (13.4 ± 3.7)% (P<0.01, n=12)[4].
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