Sildenafil Citrate
Sildenafil Citrate is a potent inhibitor of cGMP-specific phosphodiesterase including PDE5 with IC50 values of 3.6 nM.[1]
PDE5 (cGMP-specific phosphodiesterase type 5) is an enzyme from the phosphodiesterase class. The function of PDE5 is to accept cGMP and breaks it down. cGMP (cyclic guanosine monophosphate) is one of second messenger which is the production of guanylate cyclase. cGMP is a regulator of cellular apoptosis glycogenolysis, conductance , and ion channel. It can relaxe smooth muscle tissues. In blood vessels, It also can relaxe vascular smooth muscles, then lead to increased blood flow and vasodilation. The inhibitors of PDE5 can inhibit the degradation of cGMP, then leads to increase bloodflow to the penis. Sildenafil Citrate is used treatment of erectile dysfunction.
Sildenafil is a potent cGMP-specific phosphodiesterase. It is highly selective for PDE5. It inhibits the activity of PDE5 with an IC50 value of 3 nM in human corpus cavernosum (3.6nM in isolated rabbit platelets). At the same condition, It inhibits the activity of PDE1 and PDE3 activities with IC50s = 0.26 and 65 μM, respectively.[1] Sildenafil potently relaxed anococcygeus muscle strip swith maximum response of 100 ± 2% and a pEC50 value of 6.44 ± 0.03 in rat. Sildenafil also increased by approximately 55% the duration of nitrergic relaxations.[1, 2] Compared to the base salt, the citrate salt has pharmacokinetics and superior water solubility.[3]
References:
[1]. Teixeira CE, Priviero FB, Claudino MA, Baracat JS, De Nucci G, Webb RC, Antunes E: Stimulation of soluble guanylyl cyclase by BAY 41-2272 relaxes anococcygeus muscle: interaction with nitric oxide. Eur J Pharmacol 2006, 530(1-2):157-165.
[2]. Richalet JP, Gratadour P, Robach P, Pham I, Dechaux M, Joncquiert-Latarjet A, Mollard P, Brugniaux J, Cornolo J: Sildenafil inhibits altitude-induced hypoxemia and pulmonary hypertension. Am J Respir Crit Care Med 2005, 171(3):275-281.
[3]. Jung SY, Seo YG, Kim GK, Woo JS, Yong CS, Choi HG: Comparison of the solubility and pharmacokinetics of sildenafil salts. Arch Pharm Res 2011, 34(3):451-454.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 666.7 |
| Cas No. | 171599-83-0 |
| Formula | C22H30N6O4S·C6H8O7 |
| Solubility | ≥25.35 mg/mL in DMSO; insoluble in EtOH; ≥2.97 mg/mL in H2O with gentle warming and ultrasonic |
| Chemical Name | 5-[2-ethoxy-5-(4-methylpiperazin-1-yl)sulfonylphenyl]-1-methyl-3-propyl-4H-pyrazolo[4,3-d]pyrimidin-7-one;2-hydroxypropane-1,2,3-tricarboxylic acid |
| SDF | Download SDF |
| Canonical SMILES | CCCC1=NN(C2=C1NC(=NC2=O)C3=C(C=CC(=C3)S(=O)(=O)N4CCN(CC4)C)OCC)C.C(C(=O)O)C(CC(=O)O)(C(=O)O)O |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
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Cell lines |
PASMCs |
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Preparation method |
The solubility of this compound in DMSO is > 25.4 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
1 μM |
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Applications |
In PASMCs, pretreatment with 1 μM Sildenafil Citrate increased the phosphorylation of ERK1/ERK2, the percentage of cells in S phase, as well as cell proliferation, compared with serotonin stimulation alone. Furthermore, pretreatment with 10 μM U0126 for 30 mins prevented Sildenafil Citrate-induced increases in the phosphorylation of ERK1/ERK2, and abolished Sildenafil Citrate-induced cell cycle progression and PASMC proliferation. |
| Animal experiment [2]: | |
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Animal models |
Hypercholesterolemic MetS rabbits |
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Dosage form |
5 mg/kg/day; p.o. |
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Applications |
In hypercholesterolemic MetS rabbits, Sildenafil Citrate inhibited the development of endothelial dysfunction and Erectile dysfunction (ED). Moreover, Sildenafil Citrate significantly improved relaxation responses of cavernosal tissues. In addition, compared with the control group, Sildenafil Citrate maintained the in vitro erectile responses of the corporal tissue strips in MetS rabbits. |
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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. |
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References: [1]. Li BB, Jiang Z, Sheng JY, Yao K. Sildenafil potentiates the proliferative effect of porcine pulmonary artery smooth muscle cells induced by serotonin in vitro. Chin Med J (Engl). 2011 Sep;124(17):2733-40. [2]. Erden Y, Korgal E, Dundar G, Ayan S, Gokce G, Yildirim S, Gultekin EY. In-vitro effects of PDE5 inhibitor and statin treatment on the contractile responses of experimental MetS rabbit's cavernous smooth muscle Arch Ital Urol Androl. 2014 Mar 28;86(1):33-8. |
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Quality Control & MSDS
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Chemical structure
