1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemESildenafil citrateCat. No.: HY-15025ACAS No.: 171599-83-0Synonyms: UK-92480 citrate分式: CHNOS分量: 666.7作靶點(diǎn): Phosphodiesterase (PDE); Autophagy作通路: Metabolic Enzyme/Protease; Autophagy儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -8

2、0C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 29 mg/mL (43.50 mM)H2O : 2 mg/mL (3.00 mM; Need ultrasonic)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)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(qǐng)根據(jù)產(chǎn)品在不同溶劑中

3、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。BIOLOGICAL ACTIVITY物活性 Sildenafil citrate種有效的磷酸酯酶 5 (PDE5)抑制劑，IC50 為 5.22 nM。IC50 & Target IC50: 5.22 nM (PDE 5) 11/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE體外研究 Pretreatment with 1 M Sildenafil citrate potentiates the phosphorylation of ERK1/ERK2, an increase

4、in thepercentage of cells in S phase and cell proliferation, compared with serotonin stimulation alone (P 2.體內(nèi)研究 In the dog model of erection, Sildenafil citrate significantly increases ICP and ICP/BP but shows nosignificant effect on BP compared with vehicle 1. Sildenafil treatment significantly de

5、creases the number ofTL+-cells at 10 but not 0.5 mg/kg. At this time point, cells positive for the M1-like marker COX-2+ are found inthe ischemic core in PBS-treated animals, whereas they are mostly observed in the penumbra in 10 mg/kg(but not 0.5 mg/kg) Sildenafil-treated animals. In contrast, 8 da

6、ys after pMCAo the number ofmicroglia/macrophages stained by Iba-1 are significantly reduced by Sildenafil treatment (0.5 and/or 10mg/kg dose) 3. Sildenafil citrate has been reported to decrease flap necrosis in preclinical animal models byincreasing the secretion of growth factors (FGF and VEGF), a

7、nd histologically is shown to be effective in ratcavernous nerve architecture 4.PROTOCOLCell Assay 2 Cells at approximately 90% confluence are harvested with 0.1% trypsin/0.01% ethylene diamine tetraaceticacid (EDTA) solution and seeded into a 96-well plate at a density of 2104 cells/well and grown

8、in RPMI-1640 containing 10% FBS for three days, followed by serum starvation for three days. Cells are thenincubated for different time with various concentration of serotonin or 1 M Sildenafil followed by serotoninwith or without U0126, as indicated. Control cells are treated in the same way except

9、 sterile PBS replacedthe drug. After treatment, medium is changed to fresh medium, and cells are incubated with 5 g/L of MTT forfour hours. MTT is then dissolved with 150 L of 10% DMSO for 20 minutes. The optical densities (OD) in the96-well plates are determined using a microplate reader at 570 nm

10、2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 3Administration 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

11、.p.) injections. In the first set ofexperiments, animals are randomly divided into five groups and treated with either PBS or a single dose ofSildenafil citrate (0.5, 2.5, 10, and 15 mg/kg), given intraperitoneally (i.p.) 5 min after pMCAo. In the secondset of experiments, animals are randomly divid

12、ed into three groups and treated with either PBS or a singledose of Sildenafil citrate (0.5 and 10 mg/kg, i.p.) 5 min after pMCAo.Rats 4Thirty male Sprague-Dawley rats weighing between 210 and 240 g are used. Rats from all groups areanesthetized with xylazine + ketamine and then a crush injury is cr

13、eated by using a one-minute long vascularclamp to the right sciatic nerve. One day before the procedure, rats from Group 1 are started on a 28-daytreatment consisting of a daily dose of 20 mg/kg body weight Sildenafil given orally via nasogastric tube,while the rats from Group 2 are started on an ev

14、ery-other-day dose of 10 mg/kg body weight Sildenafilcitrate. Rats from Group 3 did not receive any drugs. Subjects in all 3 groups are fed ad libitum with normalrat chow and tap water. Forty-two days after the nerve damage is created, the rats underwent a static sciaticindex (SSI) test, sedation an

15、d motor coordination tests, and accelerated rotarod tests. Rats are sacrificedunder anesthesia and their sciatic nerves are removed surgically. Histopathologic analyses of the nerves andbone densitometry evaluation of the extremities are then performed.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChe

16、mEMCE 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 p

17、ulmonary artery smooth muscle cells induced by serotonin in vitro.Chin Med J (Engl). 2011 Sep;124(17):2733-40.3. Moretti R, et al. Sildenafil, a cyclic GMP phosphodiesterase inhibitor, induces microglial modulation after focal ischemia in the neonatalmouse brain. J Neuroinflammation. 2016 Apr 28;13(1):95.4. Korkmaz MF, et al. The Effect of Sildenafil on Recuperation from Sciati