| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
PDE5/phosphodiesterase 5
Thiosildenafil is presumed to target phosphodiesterase type 5 (PDE5), the enzyme responsible for the degradation of cyclic guanosine monophosphate (cGMP) in the corpus cavernosum of the penis and pulmonary vasculature. By inhibiting PDE5, thiosildenafil leads to increased cGMP levels, resulting in smooth muscle relaxation and vasodilation. The compound functions through the nitric oxide (NO)-cGMP signaling pathway, similar to its parent compound sildenafil. Specific binding affinity and IC50 data for thiosildenafil at PDE5 are not fully characterized in published literature. |
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| ln Vitro |
iErect, a new dietary supplement marketed as "100% natural" and sold over the Internet, was analyzed. It contains thiosildenafil, a sildenafil analogue already reported as an adulterant in herbal formulations, and a new compound whose structure was elucidated after isolation using NMR, MS and IR. It was named depiperazinothiosildenafil as it results from the hydrolytic cleavage of the S-N bond of the sulfonamide group of thiosildenafil. A capsule of iErect contains a very high amount (≈220mg) of thiosildenafil and ≈30mg of depiperazinothiosildenafil, which places consumers at risk for potentially serious side-effects[1].
In vitro activity data for thiosildenafil are limited, as it has not undergone formal drug development. Based on its structural analogy to sildenafil, it is presumed to inhibit PDE5 enzyme activity in cell-free assays, though the sulfur substitution may alter potency compared to the parent compound. The compound is primarily detected and quantified in adulterated supplement samples using analytical techniques including LC-MS and NMR, rather than being characterized in cell-based functional assays for pharmacological activity. |
| ln Vivo |
In vivo activity and pharmacokinetic data for thiosildenafil are not formally characterized. The compound has been identified in consumer health supplements, suggesting its presence in products intended for oral consumption. Based on analogy to sildenafil, it may exhibit oral bioavailability, be absorbed from the gastrointestinal tract, and distribute to systemic circulation. However, no controlled animal studies have been published to confirm its in vivo PDE5 inhibitory efficacy, hemodynamic effects, or duration of action.
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| Enzyme Assay |
Cell-free PDE5 inhibition assay protocol (general for PDE5 inhibitors): Human recombinant PDE5 enzyme is incubated with varying concentrations of test compound and [3H]-cGMP substrate in assay buffer for 30-60 minutes at room temperature. The reaction is terminated by boiling or adding stop solution containing zinc sulfate and barium hydroxide. The amount of [3H]-guanosine produced is quantified by scintillation counting after separation from unreacted cGMP. IC50 values are calculated from dose-response curves. This protocol has not been validated specifically for thiosildenafil.
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| Cell Assay |
Cell-based assays for PDE5 inhibitors generally use smooth muscle cells (e.g., human corpus cavernosum smooth muscle cells or pulmonary artery smooth muscle cells). Cells are treated with compound, and cGMP levels are measured by ELISA after stimulation with nitric oxide donors (e.g., sodium nitroprusside). Alternatively, cell viability or relaxation assays may be performed. However, these methods have not been specifically published for thiosildenafil, which is primarily an analytical standard rather than a validated pharmacological tool.
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| Animal Protocol |
Controlled in vivo animal studies for thiosildenafil are not available in peer-reviewed literature. For PDE5 inhibitor research in general, animal protocols involve administering compounds to rats or mice via oral gavage, followed by measurement of blood pressure, penile tumescence (electrically stimulated erection models), or pulmonary artery pressure. cGMP levels in tissues are quantified by ELISA. Such studies have not been conducted or reported for thiosildenafil specifically, as it is not a drug candidate.
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| ADME/Pharmacokinetics |
Formal pharmacokinetic studies have not been conducted for thiosildenafil. Based on its structural similarity to sildenafil, which has a molecular weight of 474.6 g/mol and moderate lipophilicity (logP ~1.2-2.0), thiosildenafil is expected to exhibit oral absorption, extensive plasma protein binding (~96% for sildenafil), and metabolism primarily via CYP3A4-mediated oxidation. The sulfur substitution may alter the metabolic stability and plasma half-life compared to sildenafil. However, no empirical PK data are available.
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| Toxicity/Toxicokinetics |
Formal toxicological studies have not been conducted for thiosildenafil as it is not a pharmaceutical product. As an adulterant identified in health supplements, its safety profile is unknown. Based on its structural similarity to sildenafil, potential adverse effects may include headache, flushing, dyspepsia, nasal congestion, visual disturbances, and hypotension. Cardiotoxicity risks may exist, particularly in individuals taking nitrates. The sulfur substitution could introduce additional toxicological liabilities not present in sildenafil. Regulatory agencies have issued warnings about thiosildenafil in unapproved supplements.
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| References |
[1]. Lee ES, et al. Simultaneous determination of 38 phosphodiestrase-5 inhibitors in illicit erectile dysfunction products by liquid chromatography-electrospray ionization-tandem mass spectrometry. J Pharm Biomed Anal. 2013 Sep;83:171-8.
[2]. Vaysse J, et al. Identification of a novel sildenafil analogue in an adulterated herbal supplement. J Pharm Biomed Anal. 2012 Feb 5;59:58-66. |
| Additional Infomation |
This article describes the application of liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) for the simultaneous analysis of 38 compounds (including sildenafil, tadalafil, vardenafil, and their analogues) in products for illegitimate erectile dysfunction (ED). Chromatographic separation was performed on a C18 reversed-phase column with mobile phase A being 2 mM ammonium formate aqueous solution and mobile phase B being acetonitrile (ACN), using gradient elution. All components were monitored using timed multiple reaction monitoring (MRM) mode. The limits of detection (LOD) ranged from 0.004 ng/mL to 0.455 ng/mL, and the limits of quantitation (LOQ) ranged from 0.012 ng/mL to 1.5 ng/mL. Calibration curves were linear, with correlation coefficients greater than 0.9991. The average recoveries ranged from 73.6% to 111.3%, with relative standard deviations (RSDs) less than 10%. Intra-day precision ranged from 0.2% to 16.3%, and inter-day precision ranged from 0.2% to 17.0%. This method has been applied to the detection of 52 types of illicit erectile dysfunction (ED) products. [1]
Thiosildenafil is not an approved pharmaceutical and has no clinical indications. It was first isolated from health supplements as an undeclared PDE5 inhibitor analogue and adulterant. It serves as an analytical standard and reference material for regulatory and forensic laboratories to screen for undeclared synthetic PDE5 inhibitors in herbal products marketed for erectile dysfunction. The compound's identification relies on MS, NMR, UV, and IR spectroscopy. It is a research-grade compound only and prohibited for human consumption in regulated markets. |
| Molecular Formula |
C22H30N6O3S2
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|---|---|
| Molecular Weight |
490.64
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| Exact Mass |
490.182
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| Elemental Analysis |
C, 53.86; H, 6.16; N, 17.13; O, 9.78; S, 13.07
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| CAS # |
479073-79-5
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| PubChem CID |
10228242
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
676.1±65.0 °C at 760 mmHg
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| Flash Point |
362.7±34.3 °C
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| Vapour Pressure |
0.0±2.1 mmHg at 25°C
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| Index of Refraction |
1.679
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| LogP |
1.79
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
33
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| Complexity |
840
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCCC1=NN(C)C2=C1N=C(C3=C(C=CC(=C3)S(=O)(=O)N4CCN(C)CC4)OCC)NC2=S
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| InChi Key |
LJUBVCQVNMLSTQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H30N6O3S2/c1-5-7-17-19-20(27(4)25-17)22(32)24-21(23-19)16-14-15(8-9-18(16)31-6-2)33(29,30)28-12-10-26(3)11-13-28/h8-9,14H,5-7,10-13H2,1-4H3,(H,23,24,32)
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| Chemical Name |
5-[2-ethoxy-5-(4-methylpiperazin-1-yl)sulfonylphenyl]-1-methyl-3-propyl-4H-pyrazolo[4,3-d]pyrimidine-7-thione
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| Synonyms |
Thiosildenafil; 479073-79-5; Sulfosildenafil; HRL3FWK7XV; UNII-HRL3FWK7XV; 5-[2-ethoxy-5-(4-methylpiperazin-1-yl)sulfonylphenyl]-1-methyl-3-propyl-4H-pyrazolo[4,3-d]pyrimidine-7-thione; DTXSID30197336; 5-(2-ETHOXY-5-((4-METHYL-1-PIPERAZINYL)SULFONYL)PHENYL)-1,6-DIHYDRO-1-METHYL-3-PROPYL-7H-PYRAZOLO(4,3-D)PYRIMIDINE-7-THIONE;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0382 mL | 10.1908 mL | 20.3815 mL | |
| 5 mM | 0.4076 mL | 2.0382 mL | 4.0763 mL | |
| 10 mM | 0.2038 mL | 1.0191 mL | 2.0382 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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