KN-62 | CAS:127191-97-3

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Name:KN-62; 
Cat. No. :CS-0516
CAS No. :127191-97-3
Formula:C38H35N5O6S2
M. Wt. : 721.84
Solubility:10 mM in DMSO

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.IC50 & Target: IC50: 0.9 μM (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 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.) (p2 treatment [F(1,28)=0.84, p>0.05] and a significant effect of KN-62×ZnCl2 treatment interaction [F(1,28)=22.57, p2 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].

Ravi RG, et al. Potent P2X7 Receptor Antagonists: Tyrosyl Derivatives Synthesized Using a Sequential Parallel Synthetic Approach. Drug Dev Res. 2001 Oct;54(2):75-87. Gargett CE, et al. The isoquinoline derivative KN-62 a potent antagonist of the P2Z-receptor of human lymphocytes. Br J Pharmacol. 1997 Apr;120(8):1483-90. Manosso LM, et al. Antidepressant-like effect of zinc is dependent on signaling pathways implicated in BDNF modulation. Prog Neuropsychopharmacol Biol Psychiatry. 2015 Jun 3;59:59-67.