KN-92 phosphate is an inactive derivative of KN-93. KN-93 is a selective inhibitor of Ca2+/calmodulin-dependent kinase II (CaMKII), competitively blocking CaM binding to the kinase (Ki = 370 nM).
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KN-92 phosphate is an inactive derivative of KN-93, without CaM kinase inhibitory activity[3]. Incubation of 10 micromol/L KN-93 induced the cell growth reduction in a time-dependent manner from 78.27% at 8 h to 11.48% at 48 h. However, KN-92, an inactive derivative of KN-93, did not inhibit cell proliferation effectively[4]. Inhibition of Ca2+/calmodulin kinase (KN-63, KN-92; 5 microM) reduced Cl--conductance in 50% of the cells investigated without affecting [Ca2+]i[5]. The CaMKII inhibitor, KN-93 (N-[2-(N-(4-Chlorocinnamyl)-N-methylaminomethyl)phenyl]-N-[2-hydroxyethyl]-4-methoxybenzenesulfonamide), but not the inactive isomer, KN-92 (2-[N-(4-Methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzylamine, phosphate), blocked clozapine's augmenting effect on NMDA-evoked responses in pyramidal cells of the rat mPFC. KN-93 also inhibited the facilitatory effect of clozapine on electrically evoked responses in the pyramidal cells, while KN-92 did not show any effect[6].
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