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1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemESDMACat. No.: HY-101410CAS No.: 30344-00-4Synonyms: Symmetric dimethylarginine; NG,NG-Dimethyl-L-arginine分式: CHNO分量: 202.25作靶點: Endogenous Metabolite作通路: Metabolic Enzyme/Protease儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C
2、 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 50 mg/mL (247.22 mM; ultrasonic and adjust pH to 3 with 1M HCl)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 4.9444 mL 24.7219 mL 49.4438 mL5 mM 0.9889 mL 4.9444 mL 9.8888 mL10 mM 0.4944 mL 2.4722 mL 4.9444 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度,選擇合適的溶劑配制儲備液,并請注意儲備液的保存式和期限。體內(nèi)實驗
3、請根據(jù)您的實驗動物和給藥式選擇適當?shù)娜芙獍?,配制前請先配制澄清的儲備液,再依次添加助溶?為保證實驗結(jié)果的可靠性,體內(nèi)實驗的作液,建議您現(xiàn)現(xiàn)配,當天使;澄清的儲備液可以根據(jù)儲存條件,適當保存;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. 請依序添加每種溶劑: 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (12.36 mM); Clear solution2. 請依序添加每種溶劑: 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (1
4、2.36 mM); Clear solution3. 請依序添加每種溶劑: 10% DMSO 90% corn oil1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemESolubility: 2.5 mg/mL (12.36 mM); Suspended solution; Need ultrasonicBIOLOGICAL ACTIVITY物活性 SDMA (Symmetric dimethylarginine)氧化氮 (NO) 合酶活性的內(nèi)源性抑制劑。IC50 & Target Human Endogenous Metabolite體外研究
5、SDMA is the structural isomer of the cardiovascular risk marker asymmetric dimethylarginine, as anendogenous marker of renal function. SDMA does not directly inhibit NOS but is a competitor of argininetransport. SDMA is primarily eliminated by renal excretion and is a promising endogenous marker ofg
6、lomerular filtration rate 1. SDMA inhibits dose dependently the NO synthesis in intact endothelial cells,whereas it has no effect on protein expression of NOS 1. SDMA is involved in the inflammatory process ofchronic kidney disease, activating NF-B and resulting in enhanced expression of IL-6 and TN
7、F- 2.體內(nèi)研究 SDMA is highly stable in serum and plasma, and the assay demonstrates excellent analytical performance.In unaffected dogs, SDMA remains unchanged whereas in affected dogs, SDMA increases during diseaseprogression, correlating strongly with an increase in sCr and decrease in GFR 3. Chronic
8、SDMA infusionleads to a significant increase of SDMA levels in mice, but the GFR did not change at 4 weeks. Nohistological changes are observed, particularly no effect on fibrosis or endothelias nitric oxide synthaseexpression. There is neither an effect of SDMA on systolic blood pressure nor on eje
9、ction fraction 4.PROTOCOLCell Assay 2 SDMA stock solution is prepared in 0.9% NaCl and diluted in the cell culture medium or in heparinized wholeblood resulting in a maximal uremic concentration of 6.1 M SDMA. Whole blood is incubated with saline(control) or different doses of ADMA (0.6, 3.6, and 36
10、 M) or SDMA (1.5, 3.1, and 6.1 M) for 2 hours in ahumidified atmosphere of 5% CO2 in air at 37C. Cells are finally stained for intracellular TNF- or IL-6.Samples are analyzed with a flow cytometer 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal
11、 Mice: Eight-week-old male C57Bl/6 mice receives vehicle-controlled infusion of SDMA (250 mol/kg/days) forAdministration 4 28 days using osmotic minipumps (n=24/group). Glomerular filtration rate, cardiac function and bloodpressure are monitored. Blood samples for SDMA determination are obtained at
12、baseline, 2 and 4 weeks.Mice are euthanized at 4 weeks to obtain tissue for renal histology 4.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Bode-B?ger SM,et al. Symmetrical dimethylarginine: a new combined parameter for renal function and
13、 extent ofcoronary artery disease.2. Schepers E, et al. Symmetric dimethylarginine as a proinflammatory agent in chronic kidney disease.Clin J Am Soc Nephrol. 2011Oct;6(10):2374-83.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE3. Nabity MB, et al. Symmetric Dimethylarginine Assay Validation, Stab
14、ility, and Evaluation as a Marker for the EarlyDetection of ChronicKidney Disease in Dogs. J Vet Intern Med. 2015 Jul-Aug;29(4):1036-44.4. Veldink H, et al. Effects of chronic SDMA infusion on glomerular filtration rate, blood pressure, myocardial function and renal histology inC57BL6/J mice. Nephrol Dial Transplant. 2013 Jun;28(
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