KN-93 Phosphate |
| カタログ番号GC12804 |
KN-93 リン酸は、精製されたニューロン CaMK-II の新規な膜透過性合成阻害剤であり、Ki は 370 nM です。
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1188890-41-6
Sample solution is provided at 25 µL, 10mM.
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KN-93 phosphate is the water soluble form of KN-93. It is a potent, selective and cell permeable inhibitor of CaM kinase II (IC50= 0.37 μm, Ki=370 nm) [1]
CaMK II (calcium/calmodulin-dependent protein kinase II) is a multifunctional serine/threonine kinase with various roles in different physiological systems.
Since CaMK II can enhance cell proliferation, the CaMK II inhibitor KN-93 blocked the cell proliferation by regulating the expression of p53 and p21 in human hepatic stellate cells. [2] KN-93 inhibited the autophosphorylation of both α and β subunits of CaMK II. Moreover, KN-93 reduced dopamine level via modulating the TH reaction rate to reduce the Ca2+-mediated phosphorylation levels of the TH molecule in PC12h cells.[1] As CaMK II is necessary for cell cycle progression through G1, KN-93 also induced G1 cell cycle arrest and apoptosis in NIH 3T3 cells.[3]
In MRL/lpr Foxp3-GFP mice, KN-93 promoted the generation of Foxp3 regulatory T cells through the inhibition of CaMK IV in the spleen, peripheral lymph nodes and peripheral blood with decreased skin and kidney damage. [4] In a rat model of Parkinson's disease, intrastriatal injection of KN-93 relieved the levodopa-induced dyskinesia by suppressing the CaMK II activation. [5]
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] An P, Zhu JY, Yang Y, Lv P, Tian YH, Chen MK, Luo HS. 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.
[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 Sep;6(9):1063-70.
[4] Koga T, Mizui M, Yoshida N, Otomo K, Lieberman LA, Crispín JC, Tsokos GC.KN-93, an inhibitor of calcium/calmodulin-dependent protein kinase IV, promotes generation and function of Foxp3⁺ regulatory T cells in MRL/lpr mice. Autoimmunity. 2014 Nov;47(7):445-50.
[5] 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. doi: 10.2147/NDT.S45422.
| Cell experiment [1]: | |
|
Cell lines |
Human hepatic stellate cell line LX-2 |
|
Preparation method |
Soluble in DMSO >30mg/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. |
|
Reacting condition |
5, 10, 25, 50μmol/L for 24h; 10 μmol/L for 4, 8, 16, 24, 48h |
|
Applications |
KN-93 decreased the proliferation of human hepatic stellate cells in a dose dependent manner after 24 h treatment. Incubation of 10 μmol/L KN-93 induced the cell growth reduction in a time-dependent manner. KN-93 reduced the expression of p53 and p21. |
| Animal experiment [2]: | |
|
Animal models |
adult Sprague Dawley female rats (model of PD was induced by 6-hydroxydopamine (OHDA)) |
|
Dosage form |
1μg, 2μg, or 5μg KN-93, intrastriatal injections |
|
Application |
The data indicated that intrastriatal injections of KN-93 were beneficial in reducing the expression of LID (levodopa-induced dyskinesia) by lowering the expression of pGluR1S845(Phosphorylated GluR1(Glutamate receptor 1) at Serine-845) via suppressing the activation of CaMKII (calcium -dependent protein kinase II) in PD rats. Decreased expression of pGluR1S845 further reduced the expression of Gad1(glutamate decarboxylase 1) and nr4a1(nuclear receptor subfamily 4, group A, member 1) in PD rats. |
|
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. |
|
References: [1]. An P, Zhu JY, 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. [2]. Yang X, Wu N, et al, Intrastriatal injections of KN-93 ameliorates levodopa-induced dyskinesia in a rat model of Parkinson's disease. Neuropsychiatr Dis Treat. 2013;9:1213-20. doi: 10.2147/NDT.S45422. | |
| Cas No. | 1188890-41-6 | SDF | |
| Canonical SMILES | CN(C/C=C/C1=CC=C(Cl)C=C1)CC2=CC=CC=C2N(CCO)S(C3=CC=C(OC)C=C3)(=O)=O.O=P(OO)=O.[HH] | ||
| Formula | C26H32ClN2O8PS | M.Wt | 599.03 |
| 溶解度 | ≥ 29.95mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.6694 mL | 8.3468 mL | 16.6937 mL |
| 5 mM | 0.3339 mL | 1.6694 mL | 3.3387 mL |
| 10 mM | 0.1669 mL | 0.8347 mL | 1.6694 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 8 reference(s) in Google Scholar.)
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