KN-62

127191-97-3

C38H35N5O6S2

DMSO : >= 100 mg/mL (138.53 mM); H2O : < 0.1 mg/mL (insoluble)

Neuronal Signaling; Membrane Transporter/Ion Channel

KN-62 is a selective and potent inhibitor of calmodulin-dependent protein kinase II (CaMK-II) with IC₅₀ of 0.9 uM, KN-62 also displays noncompetitive antagonism at P2X₇ receptors in HEK293 cells, with an IC₅₀ value of approximately 15 nM. IC50 & Target: IC50: 0.9 uM (CaMK II)^[1], 15 nM (P2X₇ receptor, in HEK293 cells)^[2] 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 uM has no effect on ATP-induced ethidium influx through the rat P2X₇ receptor, while the IC₅₀ at the human P2X₇ receptor is 0.1 uM. 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 ug/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-62xZnCl₂ 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-62xZnCl₂ treatment interaction [F(1, 24)=0.61, p>0.05])^[3].