KN-62

KN-62 is a selective and reversible inhibitor of calmodulin-dependent protein kinase II (CaMK-II) with a K_i of 0.9 μM for rat brain CaMK-II. KN-62 directly binds to the calmodulin binding site of CaMK-II. KN-62 displays noncompetitive antagonism at P2X₇ receptors in HEK293 cells, with an IC₅₀ value of approximately 15 nM. In Vitro: KN-62 potently antagonizes ATP-stimulated Ba²⁺ influx into fura-2 loaded human lymphocytes with an IC₅₀ of 12.7 nM and complete inhibition of the flux at a concentration of 500 nM^[1].
KN-62 does not inhibit the activity of autophosphorylated Ca2+/CaM kinase II. KN-62 inhibits the Ca2+/calmodulin-dependent autophosphorylation of both alpha (50 kDa) and beta (60 kDa) subunits of Ca2+/CaM kinase II dose dependently in the presence or absence of exogenous substrate^[2].
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^[4]. In Vivo: KN62 (5 mg/kg/day; ip; three times a week for 6 weeks) significantly reduces the liver metastatic tumor burden in five weeks old BALB/c athymic nude mice inoculated with TAMR-MCF-7 cells^[3].
KN-62 (1 μg/site, i.c.v.) prevents the antidepressant-like behavior and antidepressant-like behaviors of ZnCl₂ (10 mg/kg, p.o.)^[5].