1. Metabolic Enzyme/Protease Vitamin D Related/Nuclear Receptor Immunology/Inflammation Stem Cell/Wnt Apoptosis
  2. Phosphodiesterase (PDE) Glucocorticoid Receptor Wnt β-catenin Apoptosis
  3. Mirodenafil dihydrochloride

Mirodenafil dihydrochloride  (Synonyms: SK-3530 dihydrochloride)

Cat. No.: HY-14930A Purity: 99.85%
COA Handling Instructions

Mirodenafil (SK3530) dihydrochloride is an orally active, potent, reversible, and selective phosphodiesterase 5 (PDE5) inhibitor. Mirodenafil dihydrochloride is a glucocorticoid receptor (GR) modulator Mirodenafil dihydrochloride activates the Wnt/β-catenin signaling pathway by downregulating Dkk1 expression. Mirodenafil dihydrochloride can be used for the research of erectile dysfunction (ED), Alzheimer’s disease (AD) and systemic sclerosis (SSc).

For research use only. We do not sell to patients.

Mirodenafil dihydrochloride Chemical Structure

Mirodenafil dihydrochloride Chemical Structure

CAS No. : 862189-96-6

Size Price Stock Quantity
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Solid + Solvent
10 mM * 1 mL in DMSO
ready for reconstitution
USD 74 In-stock
Solution
10 mM * 1 mL in DMSO USD 74 In-stock
Solid
5 mg USD 56 In-stock
10 mg USD 90 In-stock
50 mg USD 270 In-stock
100 mg USD 430 In-stock
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Customer Review

Based on 1 publication(s) in Google Scholar

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Description

Mirodenafil (SK3530) dihydrochloride is an orally active, potent, reversible, and selective phosphodiesterase 5 (PDE5) inhibitor. Mirodenafil dihydrochloride is a glucocorticoid receptor (GR) modulator Mirodenafil dihydrochloride activates the Wnt/β-catenin signaling pathway by downregulating Dkk1 expression. Mirodenafil dihydrochloride can be used for the research of erectile dysfunction (ED), Alzheimer’s disease (AD) and systemic sclerosis (SSc)[1][2][3].

IC50 & Target

PDE5

 

In Vitro

Mirodenafil dihydrochloride (0-40 μM, 24 h) exerts neuroprotective functions via activating the cGMP/PKG/CREB signaling pathway[2].
Mirodenafil dihydrochloride (0-40 μM, 24 h) enhances neuronal survival by protecting the mitochondrial membrane potential and inhibiting apoptosis[2].
Mirodenafil dihydrochloride (0-40 μM) inhibits GSK-3β signaling, resulting in reduced tau phosphorylation, decreased Aβ production by inhibiting amyloidogenesis and activating the autophagosomal pathway[2].
Mirodenafil dihydrochloride inhibits the transcriptional activity of the glucocorticoid receptor (GR), and inhibits homodimerization of GR in HT-22 cells[2].
Mirodenafil dihydrochloride (0-100 μM, 24 h) inhibits TGF-β-induced phosphorylation of Smad2/3 and mRNA expression of the fibrosis marker in fibroblasts[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Western Blot Analysis[2]

Cell Line: SH-SY5Y human neuroblastoma cells
Concentration: 0, 10, 20, 40 μM
Incubation Time: 24 h
Result: Significantly increased cGMP levels by about 200% in a dose-dependent manner. Reversed the Aβ-induced decrease in phosphorylated CREB in a dose-dependent manner. Aβ42 alone increased the levels of cleaved caspase-3 and cleaved PARP, whereas the combined treatment with mirodenafil markedly reduced the expression levels of both apoptotic markers.

RT-PCR[3]

Cell Line: NIH3T3 mouse embryonic fibroblasts
Concentration: 0, 10, 100 μM
Incubation Time: 24 h
Result: The mRNA expression of COL1A1, α-SMA, and CTGF were induced by treatment with TGF-β1, and Mirodenafil significantly reduced the expression of these profibrotic genes.
In Vivo

Mirodenafil dihydrochloride (4 mg/kg, IP, daily for 4 weeks) enhances the cognitive-behavioral performance in transgenic AD mice[2].
Mirodenafil dihydrochloride (0-10 mg/kg, Orally, daily for 3 weeks) ameliorates dermal fibrosis in a BLM-induced SSc mouse model by inhibiting the TGF-β signaling pathway, thereby suppressing the expression of collagen and profibrotic genes[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: APP-C105 transgenic mice (13-month-old, male, n=6)[2]
Dosage: 4 mg/kg
Administration: IP, daily for 4 weeks
Result: Improved cognitive function in the APP-C105 AD mice.
Animal Model: Male BALB/c mice (8 weeks old, four groups, n=10/group)[3]
Dosage: 0, 5 or 10 mg/kg
Administration: Orally, daily for 3 weeks
Result: Ameliorated dermal fibrosis and downregulated the protein levels of fibrosis markers including COL1A1 and α-SMA in the BLM-induced SSc mouse model. Significantly decreased dermal thickness and collagen content.
Clinical Trial
Molecular Weight

604.59

Formula

C26H39Cl2N5O5S

CAS No.
Appearance

Solid

Color

White to off-white

SMILES

[H]Cl.[H]Cl.O=C1C(N(CC)C=C2CCC)=C2N=C(C3=CC(S(=O)(N4CCN(CCO)CC4)=O)=CC=C3OCCC)N1

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

4°C, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)

Solvent & Solubility
In Vitro: 

DMSO : ≥ 100 mg/mL (165.40 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

H2O : 5 mg/mL (8.27 mM; ultrasonic and warming and heat to 60°C)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 1.6540 mL 8.2701 mL 16.5401 mL
5 mM 0.3308 mL 1.6540 mL 3.3080 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

  • Molarity Calculator

  • Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass
=
Concentration
×
Volume
×
Molecular Weight *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

×
Volume (start)

V1

=
Concentration (final)

C2

×
Volume (final)

V2

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 2.5 mg/mL (4.14 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
  • Protocol 2

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

    Solubility: ≥ 2.5 mg/mL (4.14 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

    Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
+
%
Tween-80 +
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).

*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation
References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
H2O / DMSO 1 mM 1.6540 mL 8.2701 mL 16.5401 mL 41.3503 mL
5 mM 0.3308 mL 1.6540 mL 3.3080 mL 8.2701 mL
DMSO 10 mM 0.1654 mL 0.8270 mL 1.6540 mL 4.1350 mL
15 mM 0.1103 mL 0.5513 mL 1.1027 mL 2.7567 mL
20 mM 0.0827 mL 0.4135 mL 0.8270 mL 2.0675 mL
25 mM 0.0662 mL 0.3308 mL 0.6616 mL 1.6540 mL
30 mM 0.0551 mL 0.2757 mL 0.5513 mL 1.3783 mL
40 mM 0.0414 mL 0.2068 mL 0.4135 mL 1.0338 mL
50 mM 0.0331 mL 0.1654 mL 0.3308 mL 0.8270 mL
60 mM 0.0276 mL 0.1378 mL 0.2757 mL 0.6892 mL
80 mM 0.0207 mL 0.1034 mL 0.2068 mL 0.5169 mL
100 mM 0.0165 mL 0.0827 mL 0.1654 mL 0.4135 mL

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

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  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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Mirodenafil dihydrochloride
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