KN-93 hydrochloride
目录号 : GC12501
KN-93 hydrochloride是一种有效的、细胞膜通透性的、选择性Ca2+/钙调蛋白依赖性蛋白激酶II（CaMKII）抑制剂，IC50值为0.37μM。
Cas No.:1956426-56-4
Sample solution is provided at 25 µL, 10mM.
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KN-93 hydrochloride is an effective, cell-membrane permeable, and selective inhibitor of Ca2+/calmodulin-dependent protein kinase II (CaMKII) with an IC50 value of 0.37μM[1, 2]. KN-93 hydrochloride inhibits the rapid component of the delayed rectifier potassium current (IKr) in mammalian cardiomyocytes[3]. KN-93 hydrochloride induces nuclear translocation of histone deacetylase 4 (HDAC4), thereby promoting fatty acid oxidation in myocardial infarction[4].
In vitro, treatment of LX-2 human hepatic stellate cells with KN-93 hydrochloride (0-50μM) for 24h decreased cell viability and the expression of cell cycle regulatory proteins p53 and p21 in a dose-dependent manner[5]. Treatment of NMDA-induced neuronal cells with KN-93 hydrochloride (1μM) significantly reduced cell apoptosis, LDH release, and intracellular calcium concentration[6].
In vivo, 21-day treatment of Parkinson's disease rats with KN-93 hydrochloride (2μg, 5μg) via striatal injection significantly alleviated levodopa-induced motor dysfunction, reduced phosphorylation levels of GluR1 in the nucleus accumbens, and decreased the expression levels of glutamate decarboxylase 1 (Gad1) and Nur77 (NR4A1, an orphan receptor of the nuclear receptor superfamily)[7].
References:
[1] Anderson M E, Braun A P, Wu Y, et al. KN-93 hydrochloride, an inhibitor of multifunctional Ca++/calmodulin-dependent protein kinase, decreases early afterdepolarizations in rabbit heart[J]. The Journal of pharmacology and experimental therapeutics, 1998, 287(3): 996-1006.
[2] Agulló L, Garcia-Dorado D, Escalona N, et al. Membrane association of nitric oxide-sensitive guanylyl cyclase in cardiomyocytes[J]. Cardiovascular research, 2005, 68(1): 65-74.
[3] Hegyi B, Chen-Izu Y, Jian Z, et al. KN-93 hydrochloride inhibits IKr in mammalian cardiomyocytes[J]. Journal of Molecular and Cellular Cardiology, 2015, 89: 173-176.
[4] Zhao J, Li L, Wang X, et al. KN-93 hydrochloride promotes HDAC4 nucleus translocation to promote fatty acid oxidation in myocardial infarction[J]. Experimental Cell Research, 2024, 438(2): 114050.
[5] An P, Zhu J Y, Yang Y, et al. KN-93 hydrochloride, a specific inhibitor of CaMKII inhibits human hepatic stellate cell proliferation in vitro[J]. World Journal of Gastroenterology: WJG, 2007, 13(9): 1445.
[6] Liu X, Ma C, Xing R, et al. The calmodulin-dependent protein kinase II inhibitor KN-93 hydrochloride protects rat cerebral cortical neurons from N-methyl-D-aspartic acid-induced injury☆[J]. Neural Regeneration Research, 2013, 8(2): 111-120.
[7] Yang X, Wu N, Song L, et al. Intrastriatal injections of KN-93 hydrochloride ameliorates levodopa-induced dyskinesia in a rat model of Parkinson’s disease[J]. Neuropsychiatric disease and treatment, 2013: 1213-1220.
KN-93 hydrochloride是一种有效的、细胞膜通透性的、选择性Ca2+/钙调蛋白依赖性蛋白激酶II（CaMKII）抑制剂，IC50值为0.37μM[1, 2]。KN-93 hydrochloride能够抑制哺乳动物心肌细胞中延迟整流钾电流的快速成分（IKr）[3]。KN-93 hydrochloride能够诱导组蛋白脱乙酰酶4（HDAC4）向细胞核转位，从而促进心肌梗死中的脂肪酸氧化[4]。
在体外，KN-93 hydrochloride（0-50μM）处理LX-2人肝星形细胞24h，以剂量依赖性方式降低了细胞活力，降低了细胞周期调节蛋白p53和p21的表达[5]。KN-93 hydrochloride（1μM）处理N-甲基-D-天冬氨酸（NMDA）诱导损伤的神经元细胞，显著降低了细胞凋亡率，减少了乳酸脱氢酶（LDH）释放，降低了细胞内钙离子浓度[6]。
在体内，KN-93 hydrochloride（2μg，5μg）通过纹状体注射治疗帕金森病大鼠21天，显著减轻了左旋多巴诱导的运动障碍，降低了内纹核中小鼠谷氨酸受体1（GluR1）的磷酸化水平，降低了谷氨酸脱羧酶1（Gad1）和Nur77（NR4A1，是核受体超家族的孤生受体）的表达水平[7]。
| Cell experiment [1]: | |
Cell lines | LX-2 cells |
Preparation Method | LX-2 cells were incubated with 0, 5, 10, 25, 50μM of KN-93 hydrochloride for 24h, and cell viability was then measured using the CCK-8 assay. |
Reaction Conditions | 0, 5, 10, 25, 50μM; 24h |
Applications | After incubation of KN-93 hydrochloride at various concentrations for 24h, the number of LX-2 cells reduced dramatically from 81.76% (5μM) to 27.15% (50μM). |
| Animal experiment [2]: | |
Animal models | Sprague Dawley rats |
Preparation Method | 6-hydroxydopamine (OHDA) injections were used to create a rat model of Parkinson's disease (PD). After 3 weeks of injections, rats exhibiting stable apomorphine-induced rotations (≥0.7 turns/minute) were selected as valid PD rats. Forty of these PD rats were treated with levodopa plus benserazide twice daily for 21 days. Abnormal involuntary movement (AIM) scores were measured on days 1, 7, 14, and 21 of treatment. In addition, one group of PD rats (PD group, n=10) and another group of sham-operated rats (sham group, n=10) were treated with vehicle twice daily for 21 days. On day 22, the 40 levodopa-treated PD rats were randomly divided into four groups: levodopa+KN-93 hydrochloride (1µg) group, levodopa+KN-93 hydrochloride (2µg) group, levodoap+KN-93 hydrochloride (5µg) group, and levodopa+vehicle group. These rats received intrastriatal injections of different doses of KN-93 hydrochloride (1µg, 2µg, or 5µg) or vehicle before levodopa treatment. As a control, the sham group and PD group rats received intrastriatal injections of vehicle before vehicle treatment. Apomorphine-induced rotations were measured to assess the antiparkinsonian effect of KN-93 hydrochloride on days 1 and 22. AIM scores were measured to assess the antidyskinetic effect of KN-93 hydrochloride on days 1, 7, 14, 21, and 22. At the end of the experiment, rats were euthanized with deep anesthesia using 3% phenobarbital. Western blot analysis was used to determine the levels of GluR1 and pGluR1S845. Real-time polymerase chain reaction (PCR) was used to measure the levels of Gad1 and Nurr77. |
Dosage form | 1, 2, 5μg; 21 days; intrastriatally treated |
Applications | 2µg and 5µg KN-93 hydrochloride treatment lowered AIMs scores in levodopa priming PD rats without affecting the antiparkinsonian effect of levodopa. In agreement with behavioral analysis, KN-93 hydrochloride treatment reduced pGluR1S845 levels in PD rats. Moreover, KN-93 hydrochloride treatment reduced the expression of Gad1 and Nur77 in PD rats. |
References: | |
| Cas No. | 1956426-56-4 | SDF | |
| 化学名 | (E)-N-(2-(((3-(4-chlorophenyl)allyl)(methyl)amino)methyl)phenyl)-N-(2-hydroxyethyl)-4-methoxybenzenesulfonamide hydrochloride | ||
| Canonical SMILES | CN(CC1=CC=CC=C1N(S(C2=CC=C(OC)C=C2)(=O)=O)CCO)C/C([H])=C([H])/C3=CC=C(Cl)C=C3.Cl | ||
| 分子式 | C26H30Cl2N2O4S | 分子量 | 537.5 |
| 溶解度 | ≥ 26.9mg/mL in DMSO | 储存条件 | Store 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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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.8605 mL | 9.3023 mL | 18.6047 mL |
| 5 mM | 372.1 μL | 1.8605 mL | 3.7209 mL |
| 10 mM | 186 μL | 930.2 μL | 1.8605 mL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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Quality Control & SDS
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- Purity: >99.00%
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