KN-62
(Synonyms: 1-[N,O-二(5-异喹啉磺酰基)-N-甲基-L-型酪氨酸]-4-苯基哌嗪) 目录号 : GC14202
KN-62是一种选择性钙调蛋白依赖性蛋白激酶II（CaMKII）抑制剂，同时是强效非竞争性P2X7受体拮抗剂。
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.
KN-62是一种选择性钙调蛋白依赖性蛋白激酶II（CaMKII）抑制剂，同时是强效非竞争性P2X7受体拮抗剂[1][2]。CaMKII是一种丝氨酸/苏氨酸激酶，通过磷酸化参与神经信号传导、肌肉收缩及其他细胞过程的多种底物，在钙信号转导中发挥关键作用[3]。P2X7是P2X受体家族的ATP门控离子通道，由细胞外高浓度ATP激活，介导炎症反应和细胞死亡[4]。KN-62通常用于神经信号转导、炎症反应及肿瘤转移机制的研究[5]。
在体外，KN-62（3μM；24小时）处理他莫昔芬耐药的MCF-7细胞可抑制ATP诱导的钙内流、细胞增殖和迁移，并减少小细胞外囊泡分泌及CD63表达[6]。
在体内，KN-62（1μg/位点；脑室内注射）可逆转ZnCl₂诱导的Swiss小鼠在悬尾实验中不动时间的缩短[7]。
| 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 | |
| 别名 | 1-[N,O-二(5-异喹啉磺酰基)-N-甲基-L-型酪氨酸]-4-苯基哌嗪 | ||
| 化学名 | [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 | ||
| 分子式 | C38H35N5O6S2 | 分子量 | 721.9 |
| 溶解度 | ≥ 36.1mg/mL in DMSO, ≥ 15.88 mg/mL in EtOH with ultrasonic | 储存条件 | Desiccate at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Quality Control & SDS
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- Purity: >99.00%
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