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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Targets |
Mirodenafil targets phosphodiesterase type 5 (PDE5), an enzyme that hydrolyzes cyclic GMP (cGMP) in smooth muscle cells. By inhibiting PDE5, Mirodenafil prevents the breakdown of cGMP, leading to its accumulation. This results in sustained smooth muscle relaxation, increased blood flow to the corpus cavernosum, and improved erectile function. It has an IC50 of 0.34 nM for PDE5.
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| ln Vitro |
Mirodenafil (0–40 μM, 24 hours) stimulates the cGMP/PKG/CREB signaling pathway, which has neuroprotective effects [2]. Through the inhibition of apoptosis and preservation of mitochondrial membrane potential, mirodenafil (0–40 μM) improves neuronal survival [2]. Midenafil (0–40 μM) suppresses GSK-3β signaling, which lowers tau phosphorylation and lowers the generation of Aβ by blocking the formation of amyloid and triggering the autophagosome pathway [2]. In HT-22 cells, midenafil prevents GR homodimerization and the transcriptional activity of the glucocorticoid receptor (GR) [2]. In fibroblasts, mirodenafil (0-100 μM) suppresses the phosphorylation of Smad2/3 caused by TGF-β and the mRNA expression of fibrosis markers [3].
In vitro, Mirodenafil acts as a highly potent and selective inhibitor of PDE5. It exhibits an IC50 of 0.34 nM for PDE5, indicating high potency. As a PDE5 inhibitor, it prevents the hydrolysis of cGMP, leading to increased intracellular cGMP levels in smooth muscle cells. This mechanism is the basis for its therapeutic effect in treating erectile dysfunction. |
| ln Vivo |
Transgenic AD mice can exhibit improved cognitive and behavioral performance when given an intraperitoneal injection of midenafil (4 mg/kg) once a day for 4 weeks [2]. In the BLM-induced SSc mice model, mirodenafil (0–10 mg/kg, oral, daily, for 3 weeks) improves dermis by reducing the production of profibrotic genes and collagen via blocking the TGF-β signaling pathway. fibrosis [3].
In vivo, Mirodenafil is effective in treating erectile dysfunction by enhancing blood flow to the penile tissue. It is an orally active medication. Its vasodilatory effects in the corpus cavernosum are mediated through the accumulation of cGMP and the subsequent relaxation of smooth muscle. The compound has been shown to be effective in clinical studies for the treatment of ED. |
| Enzyme Assay |
In cell-free enzymatic assays, Mirodenafil's activity is evaluated by measuring its inhibition of PDE5 enzyme activity. The enzyme (purified PDE5) is incubated with its substrate, [3H]cGMP, in the presence of varying concentrations of the compound. The amount of [3H]cGMP hydrolyzed is measured, and the IC50 is calculated from the inhibition curve. The compound's selectivity for PDE5 over other PDE isoforms (e.g., PDE1, PDE6) can also be assessed.
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| Cell Assay |
Western Blot Analysis[2]
Cell Types: SH-SY5Y Human Neuroblastoma Cells Tested Concentrations: 0, 10, 20, 40 μM Incubation Duration: 24 hrs (hours) Experimental Results: cGMP levels were Dramatically increased by approximately 200% in a dose-dependent manner. Reversal of Aβ-induced reduction in phosphorylated CREB in a dose-dependent manner. Aβ42 alone increased the levels of cleaved caspase-3 and cleaved PARP, whereas combined treatment with mironafil Dramatically diminished the expression levels of both apoptotic markers. RT-PCR[3] Cell Types: NIH3T3 mouse embryonic fibroblasts Tested Concentrations: 0, 10, 100 μM Incubation Duration: 24 h Experimental Results: TGF-β1 induced COL1A1, α-SMA and CTGF mRNA expression, and midenafil Dramatically diminished the expression of these profibrotic genes. In vitro cell-based experiments with Mirodenafil typically involve cultured smooth muscle cells, such as human corpus cavernosum smooth muscle cells. Cells are treated with the compound, and the intracellular concentration of cGMP is measured using an ELISA or radioimmunoassay (RIA). The compound's ability to increase cGMP levels in response to nitric oxide (NO) stimulation is assessed to demonstrate its PDE5 inhibitory activity. |
| Animal Protocol |
Animal/Disease Models: APP-C105 transgenic mice (13 months old, male, n=6) [2]
Doses: 4 mg/kg Route of Administration: intraperitoneal (ip) injection, one time/day for 4 weeks Experimental Results: APP-C105 AD The mice's cognitive function improved. Animal/Disease Models: Male balb/c (Bagg ALBino) mouse (8 weeks old, four groups, n=10/group) [3] Doses: 0, 5 or 10 mg/kg Route of Administration: Orally, one time/day for 3 weeks Experimental Results: Improved dermal fibrosis and downregulated protein levels of fibrosis markers, including COL1A1 and α-SMA, in BLM-induced SSc mouse model. Dermal thickness and collagen content were Dramatically diminished. In vivo animal experiments with Mirodenafil typically involve rat or mouse models of erectile dysfunction. For example, rats are administered the compound orally or intravenously, and the intracavernosal pressure (ICP) is measured in response to cavernous nerve stimulation. The increase in ICP/mean arterial pressure (MAP) ratio is used as a measure of erectile function. |
| ADME/Pharmacokinetics |
Mirodenafil is an orally active PDE5 inhibitor with favorable pharmacokinetic properties for the treatment of erectile dysfunction. As a second-generation PDE5 inhibitor, it is designed to have a rapid onset of action and a manageable duration of effect. Detailed PK parameters such as half-life, Cmax, and bioavailability are not provided in the search results but are expected to be similar to other PDE5 inhibitors.
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| Toxicity/Toxicokinetics |
Mirodenafil is generally well-tolerated in clinical use. Common adverse effects associated with PDE5 inhibitors include headache, flushing, dyspepsia, and nasal congestion. As with other PDE5 inhibitors, it is contraindicated in patients taking nitrates due to the risk of severe hypotension. The compound is for research use only and is not intended for human therapeutic use outside of approved indications.
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| References |
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| Additional Infomation |
Milodinafil belongs to the pyrrolopyrimidine class of compounds, with the chemical name 3,5-dihydro-4H-pyrrolo[3,2-d]pyrimidin-4-one. It has a 5-{[4-(2-hydroxyethyl)piperazin-1-yl]sulfonyl}-2-propoxyphenyl group at the 2-position, an ethyl group at the 5-position, and a propyl group at the 7-position. It is a type 5 phosphodiesterase inhibitor used to treat erectile dysfunction. It is both an EC 3.1.4.35 (3',5'-cyclic guanosine monophosphate phosphodiesterase) inhibitor and a vasodilator. It is classified as a sulfonamide, pyrrolopyrimidine, N-alkylpiperazine, primary alcohol, and aromatic ether drug. Milodinafil has been used in clinical trials investigating the treatment and supportive care of kidney disease, urinary tract disease, renal insufficiency, erectile dysfunction, and male erectile dysfunction.
Mirodenafil is a second-generation PDE5 inhibitor with the molecular formula C25H35N7O5S and a molecular weight of 545.65. It is also known as SK3530 and is sold under the brand name Mvix in some countries. The compound is a pyrrolopyrimidinone-based inhibitor developed by SK Chemicals. It is used for the treatment of erectile dysfunction and is available for research purposes only. |
| Molecular Formula |
C26H37N5O5S
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|---|---|
| Molecular Weight |
531.672
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| Exact Mass |
531.251
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| CAS # |
862189-95-5
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| Related CAS # |
Mirodenafil dihydrochloride;862189-96-6
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| PubChem CID |
135497803
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
730.4±70.0 °C at 760 mmHg
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| Flash Point |
395.6±35.7 °C
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| Vapour Pressure |
0.0±2.5 mmHg at 25°C
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| Index of Refraction |
1.637
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| LogP |
4.11
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
37
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| Complexity |
902
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
MIJFNYMSCFYZNY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H37N5O5S/c1-4-7-19-18-30(6-3)24-23(19)27-25(28-26(24)33)21-17-20(8-9-22(21)36-16-5-2)37(34,35)31-12-10-29(11-13-31)14-15-32/h8-9,17-18,32H,4-7,10-16H2,1-3H3,(H,27,28,33)
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| Chemical Name |
5-ethyl-2-[5-[4-(2-hydroxyethyl)piperazin-1-yl]sulfonyl-2-propoxyphenyl]-7-propyl-3H-pyrrolo[3,2-d]pyrimidin-4-one
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| Synonyms |
SK 3530 SK-3530 SK3530
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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) |
DMSO : ~125 mg/mL (~235.11 mM)
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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 | 1.8809 mL | 9.4043 mL | 18.8087 mL | |
| 5 mM | 0.3762 mL | 1.8809 mL | 3.7617 mL | |
| 10 mM | 0.1881 mL | 0.9404 mL | 1.8809 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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