KN-92 phosphate
(Synonyms: KN-92磷酸盐,KN 92 phosphate;KN92 phosphate) 目录号 : GC16981
KN-92 phosphate 是 KN-93 的无活性衍生物，没有 CaM 激酶抑制活性。 KN-92 磷酸盐旨在用作旨在阐明 KN-93 拮抗剂活性的研究中的对照化合物。 KN-93 是一种细胞渗透性、可逆性和竞争性 CaMKII 抑制剂。
Cas No.:1135280-28-2
Sample solution is provided at 25 µL, 10mM.
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KN-92 phosphate is an inactive derivative of KN-93. KN-93 is a selective inhibitor of Ca2+/calmodulin-dependent kinase II (CaMKII), competitively blocking CaM binding to the kinase (Ki = 370 nM). IC50 value:Target: KN-92 is intended to be used as a control compound in studies designed to elucidate the antagonist activities of KN-93. KN-93 inhibits histamine-induced aminopyrine uptake in parietal cells (IC50 = 300 nM). KN-93 has been used to implicate roles for CaMKII in Ca2+-induced Ca2+ release in cardiac myocytes, constitutive phosphorylation of 5-lipoxygenase in 3T3 cells, and Ca2+-dependent activation of HIF-1α in colon cancer cell.
References:
[1]. Rokhlin OW, Guseva NV, Taghiyev AF et al. KN-93 inhibits androgen receptor activity and induces cell death irrespective of p53 and Akt status in prostate cancer. Cancer Biol Ther. 2010 Feb;9(3):224-35.
[2]. Park SW, et al. CRABP1 protects the heart from isoproterenol-induced acute and chronic remodeling. J Endocrinol. 2018 Mar;236(3):151-165.
[3]. An P, Zhu JY, Yang Y et al. KN-93, a specific inhibitor of CaMKII inhibits human hepatic stellate cell proliferation in vitro. World J Gastroenterol. 2007 Mar 7;13(9):1445-8.
[4]. Gao L, Blair LA, Marshall J. et al. CaMKII-independent effects of KN93 and its inactive analog KN92: reversible inhibition of L-type calcium channels. Biochem Biophys Res Commun. 2006 Jul 14;345(4):1606-10.
[5]. Rezazadeh S, Claydon TW, Fedida D. et al. KN-93 (2-[N-(2-hydroxyethyl)]-N-(4-methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzylamine), a calcium/calmodulin-dependent protein kinase II inhibitor, is a direct extracellular blocker of voltage-gated potassium channels. J Pharmacol Exp Ther. 2006 Apr;317(1):292-9.
[6]. Anderson ME, Braun AP, Wu Y et al. KN-93, an inhibitor of multifunctional Ca++/calmodulin-dependent protein kinase, decreases early afterdepolarizations in rabbit heart. J Pharmacol Exp Ther. 1998 Dec;287(3):996-1006.
[7]. Sumi M, Kiuchi K, Ishikawa T et al. 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.
| Cell experiment [1]: | |
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Cell lines |
rabbit hypertrophic cardiac myocytes |
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Preparation method |
The solubility of this compound in DMSO is >25mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
0.5 μmol/L and 1 μmol/L |
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Applications |
KN-92 is the inactive analog of KN-93. Under the conditions of low potassium, low magnesium Tyrode’s solution perfusion, and slow frequency electrical stimulation, the incidence of early after-depolarizations (EADs) was 0/12, 11/12, 10/12, and 5/12 in sham group, left ventricular hypertrophy (LVH) group, KN-92 group (0.5 μmol/L), and KN-93 group (0.5 μmol/L), respectively. When the drug concentration was increased to 1 μmol/L in KN-92 group and KN-93 group, the incidence of EADs was 10/12 and 2/12, respectively. When the drug concentration was 0.5 μmol/L in KN-92 and KN-93 groups, the peak ICa, L at 0 mV was decreased by (9.4±2.8)% and (10.5±3.0)%, respectively. When the drug concentration was increased to 1 μmol/L, the peak ICa, L values were lowered by (13.4±3.7)% and (40±4.9)%, respectively. |
| Animal experiment [2]: | |
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Animal models |
Spontaneously hypertensive rats |
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Dosage form |
1 μmol/L |
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Application |
In spontaneously hypertensive rats, action potential duration alternans (APD-ALT) was evoked at significantly lower pacing rate, KN-93 (1 μmol/L), but not its inactive analog, KN-92 (1 μmol/L), completely reversed these changes in APD-ALT. The magnitude of APD-ALT was also significantly greater in SHR than WKY and was completely normalized by KN-93. KN-93 also abolished ventricular fibrillation (VF) induced by rapid pacing in SHR. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Ke J1, Chen F, Zhang C, et al. Effects of calmodulin-dependent protein kinase II inhibitor, KN-93, on electrophysiological features of rabbit hypertrophic cardiac myocytes. J Huazhong Univ Sci Technolog Med Sci. 2012 Aug;32(4):485-9. [2]. Mitsuyama H1, Yokoshiki H2, Watanabe M1, et al. Ca2+/calmodulin-dependent protein kinase II increases the susceptibility to the arrhythmogenic action potential alternans in spontaneously hypertensive rats. Am J Physiol Heart Circ Physiol. 2014 Jul 15;307(2):H199-206. | |
| Cas No. | 1135280-28-2 | SDF | |
| 别名 | KN-92磷酸盐,KN 92 phosphate;KN92 phosphate | ||
| 化学名 | (E)-N-(2-(((3-(4-chlorophenyl)allyl)(methyl)amino)methyl)phenyl)-4-methoxybenzenesulfonamide phosphate | ||
| Canonical SMILES | CN(CC1=CC=CC=C1NS(C2=CC=C(OC)C=C2)(=O)=O)C/C([H])=C([H])/C3=CC=C(Cl)C=C3.OP(O)(O)=O | ||
| 分子式 | C24H28ClN2O7PS | 分子量 | 554.98 |
| 溶解度 | ≥ 25 mg/mL in DMSO, ≥ 43.1 mg/mL in EtOH with gentle warming | 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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| 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 | 1.8019 mL | 9.0093 mL | 18.0187 mL |
| 5 mM | 0.3604 mL | 1.8019 mL | 3.6037 mL |
| 10 mM | 0.1802 mL | 0.9009 mL | 1.8019 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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet