KN-62 |
Catalog No.GC14202
One-Click Copy Product Info
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KN-62 is a selective calmodulin-dependent protein kinase II (CaMKII) inhibitor and also a potent non-competitive P2X7 receptor antagonist.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 127191-97-3
Sample solution is provided at 25 µL, 10mM.
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KN-62 is a selective calmodulin-dependent protein kinase II (CaMKII) inhibitor and also a potent non-competitive P2X7 receptor antagonist[1][2]. CaMKII is a serine/threonine kinase that plays a critical role in calcium signaling by phosphorylating various substrates involved in neurotransmission, muscle contraction, and other cellular processes[3]. P2X7 is an ATP-gated ion channel belonging to the P2X receptor family, which is activated by high concentrations of extracellular ATP and mediates inflammatory responses and cell death[4]. KN-62 is usually used in the research of neural signal transduction, inflammatory response and tumor metastasis mechanisms[5].
In vitro, treatment of tamoxifen-resistant MCF-7 cells with KN-62 (3μM; 24h) inhibits ATP-induced calcium influx, cell proliferation and migration, and reduces small extracellular vesicle secretion and CD63 expression[6].
In vivo, KN-62 (1μg/site; i.c.v.) reversed the ZnCl₂-induced reduction in immobility time in the tail suspension test in Swiss mice[7].
References:
[1] Schweitzer ES, Sanderson MJ, Wasterlain CG. Inhibition of regulated catecholamine secretion from PC12 cells by the Ca2+/calmodulin kinase II inhibitor KN-62. J Cell Sci. 1995;108 ( Pt 7):2619-2628.
[2] Gargett CE, Wiley JS. The isoquinoline derivative KN-62 a potent antagonist of the P2Z-receptor of human lymphocytes. Br J Pharmacol. 1997;120(8):1483-1490.
[3] Reyes Gaido OE, Nkashama LJ, Schole KL, et al. CaMKII as a Therapeutic Target in Cardiovascular Disease. Annu Rev Pharmacol Toxicol. 2023;63:249-272.
[4] Sluyter R. The P2X7 Receptor. Adv Exp Med Biol. 2017;1051:17-53.
[5] Pellicena P, Schulman H. CaMKII inhibitors: from research tools to therapeutic agents. Front Pharmacol. 2014;5:21.
[6] Park M, Kim J, Phuong NTT, et al. Involvement of the P2X7 receptor in the migration and metastasis of tamoxifen-resistant breast cancer: effects on small extracellular vesicles production. Sci Rep. 2019;9(1):11587.
[7] Manosso LM, Moretti M, Ribeiro CM, Gonçalves FM, Leal RB, Rodrigues ALS. Antidepressant-like effect of zinc is dependent on signaling pathways implicated in BDNF modulation. Prog Neuropsychopharmacol Biol Psychiatry. 2015;59:59-67.
| Cell experiment [1]: | |
Cell lines | TAMR-MCF-7 cells |
Preparation Method | TAMR-MCF-7 cells were cultured at 37°C in 5% CO2/95% air in Dulbecco’s modified Eagle’s medium (DMEM) containing 10% fetal bovine serum (FBS) and antibiotics. 5×104 cells were seeded in 96 well-plate, and cells were treated with 3μM KN-62 and 100μM ATP for 24h. The phase percentage of cells were scanned every 4h by using the IncuCyte ZOOMTM Live Cell Anaylsis System. The intracellular calcium contents were measured using a FlexStation scanning fluorimeter with an integrated fluid transfer workstation. Cell migration assay was quantified by both trans-well migration and wound healing assays. And cells were collected for further Western blot and RT-PCR analyses. |
Reaction Conditions | 3μM; 24h |
Applications | Treatment of tamoxifen-resistant MCF-7 cells with KN-62 inhibits ATP-induced calcium influx, cell proliferation and migration, and reduces CD63 expression. |
| Animal experiment [2]: | |
Animal models | Female Swiss mice |
Preparation Method | Female Swiss mice (45–55 days old, weighing 30–45g) were maintained at 20–22°C with free access to water and food, under a 12:12h light:dark cycle (lights on at 7:00 a.m.). The animals were caged in groups of 15 in a 41×34×16-cm cage. All behavioral tests were carried out between 9:00 a.m. and 04:00 p.m. Animals were acclimatized to the laboratory for at least 12h before testing. Mice were pretreated with an effective dose of ZnCl2 (10mg/kg, p.o.), and 30min later they received (i.c.v.) 1μg/site KN-62. The animals were submitted to behavioral tests 30min later (60min after zinc administration). The number of animals used for behavioral tests was 7–8 per group. The total duration of immobility induced by tail suspension was measured. Mice both acoustically and visually isolated were suspended 50cm above the floor by adhesive tape placed approximately 1cm from the tip of the tail. Mice were considered immobile only when they hung passively and completely motionless. The immobility time was recorded during a 6-min period by an experienced observer. A decreased immobility time was considered indicative of an antidepressant-like effect. |
Dosage form | 1μg/site; i.c.v. |
Applications | KN-62 reversed the ZnCl₂-induced reduction in immobility time in the tail suspension test in Swiss mice. |
References: | |
| Cas No. | 127191-97-3 | SDF | |
| Chemical Name | [4-[(2S)-2-[isoquinolin-5-ylsulfonyl(methyl)amino]-3-oxo-3-(4-phenylpiperazin-1-yl)propyl]phenyl] isoquinoline-5-sulfonate | ||
| Canonical SMILES | CN(C(CC1=CC=C(C=C1)OS(=O)(=O)C2=CC=CC3=C2C=CN=C3)C(=O)N4CCN(CC4)C5=CC=CC=C5)S(=O)(=O)C6=CC=CC7=C6C=CN=C7 | ||
| Formula | C38H35N5O6S2 | M.Wt | 721.9 |
| Solubility | ≥ 36.1mg/mL in DMSO, ≥ 15.88 mg/mL in EtOH with ultrasonic | Storage | Desiccate at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.3852 mL | 6.9262 mL | 13.8523 mL |
| 5 mM | 277 μL | 1.3852 mL | 2.7705 mL |
| 10 mM | 138.5 μL | 692.6 μL | 1.3852 mL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Quality Control & SDS
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- Purity: >99.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)