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KN-93

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Chemical Structure| 139298-40-1 同义名 : -
CAS号 : 139298-40-1
货号 : A170870
分子式 : C26H29ClN2O4S
纯度 : 98%
分子量 : 501.038
MDL号 : MFCD00236424
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(99.79 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • CaMKII

    CaMKII, Ki:0.37 μM
描述 KN-93 is a CaMKII (Calcium/calmodulin-dependent protein kinase II) blocker. It elicited potent inhibitory effects on CaMKII phosphorylating activity with an inhibition constant of 0.37μM but had no significant effects on the catalytic activity of CAMP-dependent protein kinase, Ca2+/phospholipid dependent protein kinase, myosin light chain kinase and Ca2+-phosphodiesterase. KN-93 also inhibited the autophosphorylation of both the α- and β-subunits of CaMKII. KN-93 inhibited dopamine formation by modulating the reaction rate of TH to reduce the Ca2+-mediated phosphorylation levels of the tyrosine hydroxylase molecule in PC12h cells[4]. KN-93 also works as a direct extracellular blocker of voltage-gated potassium channels with IC50 value of 307±12nM for block of the Kv1.5. KN-93 acted through promotion and stabilization of C-type inactivation. KN-93 was ineffective as a blocker when applied intracellularly, suggesting that CaMK II-independent effects of KN-93 on Kv channels can be circumvented by intracellular application of KN-93[5]. KN-93 inhibits IKr in mammalian cardiomyocytes[6].
作用机制 KN-93 inhibits CaMKII in a competitive fashion against calmodulin.[4]
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.00mL

0.40mL

0.20mL

9.98mL

2.00mL

1.00mL

19.96mL

3.99mL

2.00mL
参考文献

[1]Sumi M, Kiuchi K, 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.

[2]Rezazadeh S, Claydon TW, 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. Epub 2005 Dec 20.

[3]Hegyi B, Chen-Izu Y, et al. KN-93 inhibits IKr in mammalian cardiomyocytes. J Mol Cell Cardiol. 2015 Dec;89(Pt B):173-6.

[4]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. doi: 10.1016/0006-291x(91)92031-e. PMID: 1662507.

[5]Rezazadeh S, Claydon TW, Fedida D. 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. doi: 10.1124/jpet.105.097618. Epub 2005 Dec 20. PMID: 16368898.

[6]Hegyi B, Chen-Izu Y, Jian Z, Shimkunas R, Izu LT, Banyasz T. KN-93 inhibits IKr in mammalian cardiomyocytes. J Mol Cell Cardiol. 2015 Dec;89(Pt B):173-6. doi: 10.1016/j.yjmcc.2015.10.012. Epub 2015 Oct 14. PMID: 26463508; PMCID: PMC4689637.