西地那非檸檬酸鹽作用機制 - Medchemexpress - MCE中國

1、Product Data SheetSildenafil citrateCat. No.: HY-15025ACAS No.: 171599-83-0分式: CHNOS分量: 666.7作靶點: Phosphodiesterase (PDE); Autophagy; Apoptosis作通路: Metabolic Enzyme/Protease; Autophagy; Apoptosis儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 50 mg/mL (75.00 mM

2、; Need ultrasonic)H2O : 2 mg/mL (3.00 mM; Need ultrasonic)SolventMass1 mg 5 mg 10 mgConcentration制備儲備液1 mM 1.4999 mL 7.4996 mL 14.9992 mL5 mM 0.3000 mL 1.4999 mL 2.9998 mL10 mM 0.1500 mL 0.7500 mL 1.4999 mL請根據(jù)產品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；旦配成溶液，請分裝保存，避免反復凍融造成的產品失效。儲備液的保存式和期限：-80C, 6 months; -20C, 1 month

3、。-80C 儲存時，請在 6 個內使，-20C 儲存時，請在 1 個內使。體內實驗請根據(jù)您的實驗動物和給藥式選擇適當?shù)娜芙獍?。以下溶解案都請先按?In Vitro 式配制澄清的儲備液，再依次添加助溶劑：為保證實驗結果的可靠性，澄 的儲備液可以根據(jù)儲存條件，適當保存；體內實驗的作液，建議您現(xiàn)現(xiàn)配，當天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的式助溶1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 5 mg/mL (7.50 mM);

4、Clear solution此案可獲得 5 mg/mL (7.50 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 50.0 mg/mL 的澄 DMSO 儲備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 5 mg/mL (7.50 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 5 mg/mL (7.50

5、 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 50.0 mg/mL 的澄 DMSO 儲備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合均勻。3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 5 mg/mL (7.50 mM); Clear solution此案可獲得 5 mg/mL (7.50 mM，飽和度未知) 的澄 溶液，此案不適于實驗周 期在半個以上的實驗。以 1 mL 作液為例，取 100 L 50.0 mg/mL 的澄 DMSO 儲備液加到 900 L 油中，混合均勻。BIOLOGICAL ACT

6、IVITY物活性 Sildenafil citrate種有效的磷酸酯酶 5 (PDE5)抑制劑，IC50 為 5.22 nM。IC & Target IC50: 5.22 nM (PDE 5)1體外研究 Pretreatment with 1 M Sildenafil citrate potentiates the phosphorylation of ERK1/ERK2, an increase in thepercentage of cells in S phase and cell proliferation, compared with serotonin stimulation al

7、one (P0.05).Pretreatment with 1 M Sildenafil citrate followed by serotonin stimulation leads to dramatic increase in OD value to0.33, significantly different compared with serotonin stimulation alone (P0.05). 1 M Sildenafil obviously enhancesthe upregulation of ERK1/ERK2 phosphorylation induced by s

8、erotonin2.體內研究 In the dog model of erection, Sildenafil citrate significantly increases ICP and ICP/BP but shows no significant effect on BP compared with vehicle1. Sildenafil treatment significantly decreases the number of TL+-cells at 10 but not 0.5 mg/kg. At this time point, cells positive for th

9、e M1-like marker COX-2+ are found in the ischemic core in PBS-treatedanimals, whereas they are mostly observed in the penumbra in 10 mg/kg (but not 0.5 mg/kg) Sildenafil-treatedanimals. In contrast, 8 days after pMCAo the number of microglia/macrophages stained by Iba-1 are significantlyreduced by S

10、ildenafil treatment (0.5 and/or 10 mg/kg dose)3. Sildenafil citrate has been reported to decrease flapnecrosis in preclinical animal models by increasing the secretion of growth factors (FGF and VEGF), and histologicallyis shown to be effective in rat cavernous nerve architecture4.PROTOCOLCell Assay

11、 2 Cells at approximately 90% confluence are harvested with 0.1% trypsin/0.01% ethylene diamine tetraacetic acid(EDTA) solution and seeded into a 96-well plate at a density of 2104 cells/well and grown in RPMI-1640 containing10% FBS for three days, followed by serum starvation for three days. Cells

12、are then incubated for different time withvarious concentration of serotonin or 1 M Sildenafil followed by serotonin with or without U0126, as indicated.Control cells are treated in the same way except sterile PBS replaced the drug. After treatment, medium is changed tofresh medium, and cells are in

13、cubated with 5 g/L of MTT for four hours. MTT is then dissolved with 150 L of 10%DMSO for 20 minutes. The optical densities (OD) in the 96-well plates are determined using a microplate reader at570 nm2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Ani

14、mal Mice3Administration 34 Ischemia is induced in C57Bl/6 mice on postnatal (P) day 9 by permanent middle cerebral artery occlusion (pMCAo),and followed by either PBS or Sildenafil intraperitoneal (i.p.) injections. In the first set of experiments, animals arerandomly divided into five groups and tr

15、eated with either PBS or a single dose of Sildenafil citrate (0.5, 2.5, 10, and 15mg/kg), given intraperitoneally (i.p.) 5 min after pMCAo. In the second set of experiments, animals are randomlydivided into three groups and treated with either PBS or a single dose of Sildenafil citrate (0.5 and 10 m

16、g/kg, i.p.) 5Page 2 of 3 www.MedChemEmin after pMCAo.Rats4Thirty male Sprague-Dawley rats weighing between 210 and 240 g are used. Rats from all groups are anesthetizedwith xylazine + ketamine and then a crush injury is created by using a one-minute long vascular clamp to the rightsciatic nerve. One

17、 day before the procedure, rats from Group 1 are started on a 28-day treatment consisting of adaily dose of 20 mg/kg body weight Sildenafil given orally via nasogastric tube, while the rats from Group 2 arestarted on an every-other-day dose of 10 mg/kg body weight Sildenafil citrate. Rats from Group

18、 3 did not receive anydrugs. Subjects in all 3 groups are fed ad libitum with normal rat chow and tap water. Forty-two days after the nervedamage is created, the rats underwent a static sciatic index (SSI) test, sedation and motor coordination tests, andaccelerated rotarod tests. Rats are sacrificed

19、 under anesthesia and their sciatic nerves are removed surgically.Histopathologic analyses of the nerves and bone densitometry evaluation of the extremities are then performed.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Wang Z, et al. The Selectivity and Potency of the New PDE5 Inhibitor TPN729MA. J Sex Med. 2013 Nov;10(11):2790-7.2. Li BB, et al. Sildenafil potentiates the proliferative effect of porcine pulmonary artery smo