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KN-93

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Catalog No.
A3532
钙离子-钙调素依赖性蛋白激酶II(CaMKII)抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,300.00
Ship with 10-15 days
1mg
¥ 450.00
Ship with 10-15 days
5mg
¥ 1,160.00
Ship with 10-15 days
10mg
¥ 1,440.00
Ship with 10-15 days
25mg
¥ 3,180.00
Ship with 10-15 days

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Background

KN-93 is a potent and selective inhibitor of CaM kinase II with IC50 value of 0.37μM.[1]
CaM kinase II means Ca2+/calmodulin-dependent protein kinase II which is a serine/threonine-specific protein kinase. It is regulated by the Ca2+/calmodulin complex. CaMKII has 28 different isoforms. The structure governs an autoinhibition which is the Threonine 286 residue. When this site is phosphorylated, it will permanently activate the CaMKII enzyme. The variable and self-associative domains of CaMKII enzyme govern the sensitivity to calcium and calmodulin. CaMKII is related to many signaling pathways. CaMKII is considered to play an important role in learning and memory. CaMKII is also important for reuptake in cardiomyocytes and Ca2+ homeostasis, and CD8 T-cell activation. Misregulation of CaMKII is considered to be related to Alzheimer’s disease, heart arrhythmia , and Angelman syndrome.[2]
KN-93 significantly inhibited CaM kinase activity at 0.5μM in vitro CaM kinase assay. KN-93 potent inhibited CaM kinase II activity In vitro CaM kinase activity with rabbit myocardium with Ki value of 2.58μM. [1] KN-93 inhibited cell growth at 12μM in NIH 3T3 cells and arrested cells in G1 cycle. KN-93 induced cell apoptosis at 24μM in NIH 3T3 cells. [3] KN-93 inhibits expression of Mcl-1which is an anti-apoptotic protein, It also induces p53-independent cell death in PCa cells. KN-93 also induces  the  generation  of ROS and inhibits AR activity then induces cell death.
References:
[1].    Anderson ME, Braun AP, Wu Y, Lu T, Schulman H, Sung RJ: KN-93, an inhibitor of multifunctional Ca++/calmodulin-dependent protein kinase, decreases early afterdepolarizations in rabbit heart. J Pharmacol Exp Ther 1998, 287(3):996-1006.
[2].    Yamauchi T: Neuronal Ca2+/calmodulin-dependent protein kinase II--discovery, progress in a quarter of a century, and perspective: implication for learning and memory. Biol Pharm Bull 2005, 28(8):1342-1354.
[3].    Tombes RM, Grant S, Westin EH, Krystal G: G1 cell cycle arrest and apoptosis are induced in NIH 3T3 cells by KN-93, an inhibitor of CaMK-II (the multifunctional Ca2+/CaM kinase). Cell Growth Differ 1995, 6(9):1063-1070.

文献引用

1. Zhang Y, Zhang L, et al. "YiQiFuMai Powder Injection Attenuates Coronary Artery Ligation-Induced Heart Failure Through Improving Mitochondrial Function via Regulating ROS Generation and CaMKII Signaling Pathways." Front Pharmacol. 2019 Apr 10;10:381. PMID:31031629

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt501.04
Cas No.139298-40-1
FormulaC26H29ClN2O4S
SynonymsKN 93;KN93
Solubility≥19.15mg/mL in DMSO
Chemical NameN-[2-[[[(E)-3-(4-chlorophenyl)prop-2-enyl]-methylamino]methyl]phenyl]-N-(2-hydroxyethyl)-4-methoxybenzenesulfonamide
SDFDownload SDF
Canonical SMILESCN(CC=CC1=CC=C(C=C1)Cl)CC2=CC=CC=C2N(CCO)S(=O)(=O)C3=CC=C(C=C3)OC
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

激酶实验 [1]:

自磷酸化/非自磷酸化CaMKII的活性测定

以syntideII为底物,测定CaMKII的活性。在30°C下,将纯化的CaMKII与测试混合物(35 mM Hepes-Na ( pH 8.0),10 mM MgC12,0.5 μM CaM,5 μM ATP,1 mM CaCl2或1 mM EGTA,总体积为25 μL)混合,使其预培养2分钟。预培养后,将蛋白质底物/放射性ATP混合物加入相同的试管中,将其置于30℃下进一步培养5分钟(最终实验条件:35 mM Hepes-Na (pH 8.0),10 mM MgCl2,0.125 μM CaCl2,20 μM syntideII,11.25 μM [γ-32P] ATP,10 % DMSO和含0.25 mM CaCl2和2 mM EGTA(自我磷酸化样品)或0.25 mM EGTA和2 mM CaCl2(非自我磷酸化样品)的指定浓度KN-93,总体积为100 μL)。加入25 μL 100 % (w/v) 冰冷的TCA终止上述反应。离心后,将80 μL上清液涂覆到磷酸纤维素纸上。在连续搅动下,用75 mM H3PO4洗涤滤纸。洗涤4次后,使用液体闪烁计数器测定滤纸上的放射性残留。

细胞实验 [2]:

细胞系

NIH 3T3成纤维细胞

制备方法

在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应条件

~ 24 μM;70小时

实验结果

KN-93抑制血清诱导的成纤维细胞生长,其IC50值为8 μM。在24 μM的浓度下,KN-93导致延长的G1期阻滞,并诱导细胞凋亡。

动物实验 [3]:

动物模型

帕金森氏病 (PD) 大鼠

给药剂量

1, 2或5 μg;纹状体内给药;每日2次,持续21日

实验结果

在PD大鼠中,KN-93 (5 μg) 下调pGluR1S845表达,从而改善左旋多巴引起的运动障碍。

其它注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1]. Sumi M, Kiuchi K, Ishikawa T, Ishii A, Hagiwara M, Nagatsu T, Hidaka H. The newly synthesized selective Ca2+/calmodulin dependent protein kinase II inhibitor KN-93 reduces dopamine contents in PC12h cells. Biochem Biophys Res Commun. 1991 Dec 31;181(3):968-75.

[2]. Tombes RM, Grant S, Westin EH, Krystal G: G1 cell cycle arrest and apoptosis are induced in NIH 3T3 cells by KN-93, an inhibitor of CaMK-II (the multifunctional Ca2+/CaM kinase). Cell Growth Differ 1995, 6(9):1063-1070.

[3]. Yang X, Wu N, Song L, Liu Z. Intrastriatal injections of KN-93 ameliorates levodopa-induced dyskinesia in a rat model of Parkinson's disease. Neuropsychiatr Dis Treat. 2013;9:1213-20.

生物活性

描述 KN-93是选择性和竞争性Ca2+-钙调素依赖性蛋白激酶II(CaMKII)抑制剂,Ki值为370 nM。
靶点 CaMKII          
IC50 370 nM (Ki)          

质量控制

化学结构

KN-93

相关生物数据

KN-93