Biological Activity
KN-62 is a selective and potent inhibitor of calmodulin-dependent protein kinase II (CaMK-II) with IC50 of 0.9 μM, KN-62 also displays noncompetitive antagonism at P2X7 receptors in HEK293 cells, with an IC50 value of approximately 15 nM.
In Vitro
KN-62 is a selective antagonist of Ca2+/calmodulin-dependent protein kinase II (CaMKII). KN-62 potently antagonizes ATP-stimulated Ba2+ influx into fura-2 loaded human lymphocytes with an IC50 of 12.7±1.5 nM (n=3) and complete inhibition of the flux at a concentration of 500 nM. Similarly, KN-62 inhibits ATP-stimulated ethidium+ uptake, measured by time resolved flow cytometry, with an IC50 of 13.1±2.6 nM (n=4) and complete inhibition of the flux at 500 nM[1]. KN-62 is found to be a potent antagonist in a functional assay, inhibition of ATP-induced K+efflux in HEK293 cells expressing recombinant human P2X7 receptors. In human leukemic B lymphocytes, KN-62 reduces the rate of permeability increase to larger permeant cations, like ethidium, induced by Bz-ATP with an IC50 of 13.1 nM. KN-62 at a concentration of 3 µM has no effect on ATP-induced ethidium influx through the rat P2X7 receptor, while the IC50 at the human P2X7 receptor is 0.1 µM. KN-62 has considerable selectivity for P2X7 receptors within the P2 family[2].
In Vivo
The antidepressant-like behavior of ZnCl2 (10 mg/kg, p.o.) (p<0.01) is prevented by CAMKII inhibitor KN-62 (1 μg/site, i.c.v.). The two-way ANOVA reveals a significantly main effect of KN-62 treatment [F(1,28)=27.47, p<0.01], no main effect of ZnCl2 treatment [F(1,28)=0.84, p>0.05] and a significant effect of KN-62×ZnCl2 treatment interaction [F(1,28)=22.57, p<0.01] to immobility time. As revealed by the post-hoc analysis, the anti-immobility effect of ZnCl2 is completely prevented by treatment of animals with KN-62. No effect in locomotor activity in the open-field test is observed: (KN-62 treatment [F(1,24)=1.97, p>0.05], ZnCl2 treatment [F(1,24)=3.99, p>0.05] and KN-62×ZnCl2 treatment interaction [F(1,24)=0.61, p>0.05])[3].
References & source
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.
