[CAS NO. 862189-96-6] Mirodenafildihydrochloride
PRODUCTS SPECIFICATIONS [862189-96-6]
DESCRIPTION [862189-96-6]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 604.59 |
| Molecular Formula | C26H39Cl2N5O5S |
| SMILES | [H]Cl.[H]Cl.O=C1C(N(CC)C=C2CCC)=C2N=C(C3=CC(S(=O)(N4CCN(CCO)CC4)=O)=CC=C3OCCC)N1 |
Summary
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]
.
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. Aβ 42 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]
.
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
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT02485028 | SK Chemicals Co., Ltd. |
Drug Interaction Potentiation
|
October 2013 | Phase 1 |
| NCT01232010 | Asan Medical Center|SK Chemicals Co., Ltd. |
Renal Insufficiency|Kidney Diseases|Urologic Diseases
|
November 2009 | Phase 1 |
| NCT00351065 | SK Chemicals Co., Ltd. |
Male Erectile Dysfunction
|
September 2004 | Phase 2 |
| NCT00705861 | SK Chemicals Co., Ltd. |
Erectile Dysfunction
|
November 2007 | Phase 3 |
| NCT00489606 | SK Chemicals Co., Ltd. |
Erectile Dysfunction
|
April 2007 | Phase 1 |
| NCT00489450 | SK Chemicals Co., Ltd. |
Erectile Dysfunction
|
March 2007 | Phase 1 |
| NCT00443625 | SK Chemicals Co., Ltd. |
Erectile Dysfunction
|
December 2006 | Phase 1 |
| NCT02485041 | SK Chemicals Co., Ltd. |
Drug Interaction Potentiation
|
November 2014 | Phase 1 |
| NCT00644007 | SK Chemicals Co., Ltd. |
Erectile Dysfunction
|
December 2007 | Phase 3 |
| NCT00626743 | SK Chemicals Co., Ltd. |
Hypertension
|
May 2008 | Phase 1 |
Appearance
Solid
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
DMSO : ≥ 100 mg/mL ( 165.40 mM )
H 2 O : 5 mg/mL ( 8.27 mM ; ultrasonic and warming and heat to 60°C)
* "≥" means soluble, but saturation unknown.
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 |
| 10 mM | 0.1654 mL | 0.8270 mL | 1.6540 mL |
References
- [1] Park HJ, et al. Mirodenafil for the treatment of erectile dysfunction: a systematic review of the literature. World J Mens Health. 2014 Apr;32(1):18-27.
- [2] Kang BW, et al. Phosphodiesterase 5 inhibitor mirodenafil ameliorates Alzheimer-like pathology and symptoms by multimodal actions. Alzheimers Res Ther. 2022 Jul 8;14(1):92.
- [3] Roh JS, et al. Mirodenafil ameliorates skin fibrosis in bleomycin-induced mouse model of systemic sclerosis. Anim Cells Syst (Seoul). 2021 Nov 3;25(6):387-395.
Synonyms