KN-93 - CaMK II 抑制劑h - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEKN-93Cat. No.: HY-15465CAS No.: 139298-40-1分式: CHClNOS分量: 501.04作靶點(diǎn): CaMK作通路: Neuronal Signaling儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 50 mg/mL (99.79 mM)* means soluble, but satur

2、ation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 1.9958 mL 9.9792 mL 19.9585 mL5 mM 0.3992 mL 1.9958 mL 3.9917 mL10 mM 0.1996 mL 0.9979 mL 1.9958 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍福渲魄罢?qǐng)先配制澄清的儲(chǔ)備液，再依次添加助溶劑(為保證實(shí)驗(yàn)結(jié)果的可靠性，體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲(chǔ)備液可以根據(jù)儲(chǔ)存

3、條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 0.83 mg/mL (1.66 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 0.83 mg/mL (1.66 mM); Clear solution; Need ultrasonic and warming3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oil

4、1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemESolubility: 0.83 mg/mL (1.66 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 KN-93可滲透細(xì)胞，可逆和競(jìng)爭(zhēng)性的抑制劑鈣調(diào)蛋依賴性激酶II型 (CaMKII) 抑制劑，Ki 為370 nM。IC50 & Target Ki: 370 nM (CaMK)體外研究 After 2 days of KN-93 treatment, 95% of cells are arrested in G1. G1 arrest is reversib

5、le; 1 day after KN-93release, a peak of cells had progressed into S and G2-M. KN-93 also blocks cell growth stimulated by basicfibroblast growth factor, platelet-derived growth factor-BB, and epidermal growth factor in NIH 3T3 fibroblasts1. KN-93 inhibits the H+, K+-ATPase activity but strongly diss

6、ipates the proton gradient formed in thegastric membrane vesicles and reduces the volume of luminal space 2. KN-93 (0.5 M) prevents increasedLV developed pressure during action potential prolongation and early afterdepolarizations. Ca2+-independentCaM kinase activity is increased during early afterd

7、epolarizations and this increase is prevented by KN-933. KN-93 (10 M )significantly inhibits the activation of CaMKII/NF-B signaling induced by elevatedglucose, and subsequently decreases the expression of VEGF, iNOS and ICAM-1 in Mller cells 4.體內(nèi)研究 KN-93 (1 mg/kg/day, i.p.) inhibits retinal vascula

8、r leakage induced by diabetes, and suppressesphosphorylation of CaMKII and NF-B in diabetic retina 4.PROTOCOLCell Assay 4 Cell viability is assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay.Briefly, Mller cells are seeded at a density of 10104 cells per well i

9、n 96-well plates and cultured until sub-confluence. Next, cells are treated with curcumin for 24 h before incubation with MTT (5 mg/mL) at 37C in5% CO2 atmosphere for 4 h. The culture medium is then removed, and the formazan formed in the reactionis dissolved in 150 L DMSO. The optical density of th

10、e solution is measured at 490 nm using amultifunctional microplate reader. Cell viability in each well is presented as a percentage of the control(vehicle-treated group).MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Male Sprague-Dawley rats (8

11、weeks of age) weighing 180-200 g are used in this study. Rats are housed inAdministration 4 ventilated microisolator cages with free access to water and food. The rats are randomLy assigned to receiveeither 60 mg/kg STZ intraperitoneally or citrate buffer alone. Rats are categorized as diabetic when

12、 bloodglucose levels exceeded 16.7 mM at 48 h after STZ treatment. Two weeks after the induction of diabetes,rats are divided randomLy into three subgroups: STZ-diabetic rats (n=12), STZ-treated diabetic ratsadministered curcumin (n=12), or STZ-diabetic rats administered KN93 (n=12) for a 12-week pe

13、riod.Curcumin is suspended in saline containing 0.5% carboxymethylcellulose at a concentration of 20 mg/mLand administered via oral gavage at a total dose of 100 mg/kg/day. KN93 is administered by intraperitonealinjection at 1 mg/kg/day. Control STZ-treated diabetic rats and non-diabetic controls (n

14、=12) are gavageadministered saline containing 0.5% carboxymethylcellulose on a daily basis. Body weights and blood2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEglucose levels are measured every 2 weeks.MCE has not independently confirmed the accuracy of these methods. They are for reference only.

15、戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Cell Syst. 2018 Apr 25;6(4):424-443.e7. Diabetes. 2018 Sep;67(9):1748-1760. J Endocrinol. 2018 Mar;236(3):151-165. Acta Pharmacol Sin. 2019 Jul 17. Front Pharmacol. 2018 Apr 12;9:362.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Tombes RM, et al. G1 cell cycle arr

16、est and apoptosis are induced in NIH 3T3 cells by KN-93, an inhibitor of CaMK (the multifunctionalCa2+/CaM kinase). Cell Growth Differ. 1995 Sep;6(9):1063-70.2. Mamiya N, et al. Inhibition of acid secretion in gastric parietal cells by the Ca2+/calmodulin-dependent protein kinase II inhibitorKN-93.B

17、iochem Biophys Res Commun. 1993 Sep 15;195(2):608-15.3. Anderson ME, et al. KN-93, an inhibitor of multifunctional Ca+/calmodulin-dependent protein kinase, decreases earlyafterdepolarizations in rabbit heart. J Pharmacol Exp Ther. 1998 Dec;287(3):996-1006.4. Li J, et al. Curcumin Attenuates Retinal Vascular Leakage by Inhibiting Calcium/Calmodulin-Dependent Protein Kinase II Activity inStreptozotocin