KN-62 exhibits strong antagonism against ATP-induced Ba2+ influx in 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 hinder the activity of autophosphorylated Ca2+/CaM kinase II. It dose-dependently inhibits the Ca2+/calmodulin-dependent autophosphorylation of both alpha (50 kDa) and beta (60 kDa) subunits of Ca2+/CaM kinase II in the presence or absence of exogenous substrate[2]. KN-62 in human leukemic B lymphocytes diminishes the rate of permeability increase to larger permeant cations, such as ethidium, induced by Bz-ATP, with an IC50 of 13.1 nM[4].
体内研究
KN-62 (5 mg/kg/day; ip; three times a week for 6 weeks) markedly decreases the liver metastatic tumor burden in five-week-old BALB/c athymic nude mice inoculated with TAMR-MCF-7 cells[3].
KN-62 (1 μg/site, i.c.v.) blocks the antidepressant-like behavior and antidepressant-like effects of ZnCl2 (10 mg/kg, pO.)[5].
体外研究
KN-62 exhibits strong antagonism against ATP-induced Ba2+ influx in 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 hinder the activity of autophosphorylated Ca2+/CaM kinase II. It dose-dependently inhibits the Ca2+/calmodulin-dependent autophosphorylation of both alpha (50 kDa) and beta (60 kDa) subunits of Ca2+/CaM kinase II in the presence or absence of exogenous substrate[2].
KN-62 in human leukemic B lymphocytes diminishes the rate of permeability increase to larger permeant cations, such as ethidium, induced by Bz-ATP, with an IC50 of 13.1 nM[4].
KN-62 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Human lymphocytes
12.7 nM (IC50)
5 minutes
Inhibition of ATP-stimulated Ba2+ influx
Br J Pharmacol. 1997 Apr;120(8):1483-90.
Human B-lymphocytes
1 µM
5 min
Inhibited ATP-induced 86Rb+ efflux by 96.0%
Br J Pharmacol. 2004 Jul;142(6):1015-9.
HP cells (HEK-293 cells stably transfected with rat PROT cDNA)
25 µM
1 hour
KN-62 (CaMK II inhibitor) stimulates PRO uptake and abolishes thapsigargin inhibition, indicating PROT regulation by CaMK II.
Br J Pharmacol. 2000 Feb;129(3):465-70.
HP cells (HEK-293 cells stably transfected with rat PROT cDNA)
25 µM
1 hour
KN-62 (a CaMK II inhibitor) stimulates PRO uptake and abolishes the thapsigargin inhibitory effect, indicating that PROT is regulated by CaMK II.
Br J Pharmacol. 2000 Feb;129(3):465-70.
PBMCs
1 µM
24 hours
To evaluate the effect of KN-62 on BzATP-inhibited IL-21 production by cTfh cells. KN-62 partially rescued the IL-21 production by cTfh cells.
Front Immunol. 2024 Jul 9;15:1397098.
PBMCs
1 µM
24 hours
To evaluate the effect of KN-62 on BzATP-induced apoptosis of cTfh cells. KN-62 mitigated the apoptosis of cTfh cells induced by BzATP.
Front Immunol. 2024 Jul 9;15:1397098.
PBMCs
1 µM
3 days
To evaluate the effect of KN-62 on BzATP-inhibited proliferation of cTfh cells. KN-62 partially rescued the proliferative response of cTfh cells.
Front Immunol. 2024 Jul 9;15:1397098.
GT1-7 cells
10 µM
30 min
KN-62 prevented the histamine-induced desensitization of calcium signals in GT1-7 cells, indicating a crucial role for calcium/calmodulin-dependent protein kinase II (CaMKII) in histamine H1 receptor desensitization.
Br J Pharmacol. 1996 Jul;118(5):1119-26.
Adult skeletal muscle fibers
5 µM
30 minutes
KN-62 completely blocked the translocation of HDAC4-GFP from the nucleus to the cytoplasm induced by 10 Hz electrical stimulation
J Cell Biol. 2005 Mar 14;168(6):887-97.
HEK293 cells
86 nM (IC50)
4 min
KN-62 potently inhibited rmP2X7 receptor-mediated currents with an IC50 of 86 nM, and the inhibition was largely irreversible
Br J Pharmacol. 2011 Sep;164(2b):743-54.
Rat atria
10 µM
45 minutes
To investigate the effect of KN-62 on stimulation-induced noradrenaline synthesis, results showed that KN-62 did not affect S-I [3H]-noradrenaline synthesis.
Br J Pharmacol. 1996 Dec;119(8):1605-13.
HeLa-mPanx1 cells
10 µM
5 minutes
To evaluate the effect of CaMKII inhibition on Poly(I:C)-induced Panx1 HC activity. KN-62 preincubation completely prevented the Poly(I:C)-induced increase in DAPI uptake.
Theranostics. 2025 Jan 20;15(6):2470-2486.
Human lymphocytes
31.5 nM (IC50)
5 minutes
Inhibition of ATP-stimulated L-selectin shedding
Br J Pharmacol. 1997 Apr;120(8):1483-90.
Human lymphocytes
5.9 nM (IC50)
5 minutes
Inhibition of ATP-stimulated phospholipase D activity
Br J Pharmacol. 1997 Apr;120(8):1483-90.
Human lymphocytes
13.1 nM (IC50)
5 minutes
Inhibition of ATP-stimulated ethidium+ uptake
Br J Pharmacol. 1997 Apr;120(8):1483-90.
RAW264.7 cells
10 µM
6 hours
To evaluate the effect of CaMKII inhibition on Poly(I:C)-induced inflammatory response. KN-62 preincubation prevented the upregulation of IL-1β and TNF-α mRNA levels induced by Poly(I:C).
Theranostics. 2025 Jan 20;15(6):2470-2486.
Rat ventricular myocytes
10 µM
To investigate the inhibitory effect of KN-62 on IKATP augmented by hypoxia and GSSG. The results showed that KN-62 inhibited the IKATP augmented by hypoxia and GSSG, suggesting that the effects of both GSSG and hypoxia on KATP channels involve the activation of the CaMK II pathway.
Acta Pharmacol Sin. 2009 Oct;30(10):1399-414.
HEK-293 cells
up to 3 µM
To test the inhibitory effect of KN-62 on mouse, human, and rat P2X4 receptors, showing no concentration-dependent inhibition at any of the receptors
Br J Pharmacol. 2000 Jan;129(2):388-94.
KN-62 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Rat
Isolated rat heart ischemia/reperfusion injury model
Perfusion
3 μM
1 min before and 3 min throughout the Ca2+-free solution perfusion, as well as 3 min after restoring normal KH solution
KN-62 alleviated heart injury and calpain activity, and attenuated the binding of CAPN1 to phospho-CaMKII
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