Mirodenafil (SK3530) 是一种口服有效、可逆的、选择性的磷酸二酯酶 5 (PDE5) 的抑制剂。Mirodenafil 是一种糖皮质激素受体 (GR) 的调节剂。Mirodenafil 通过下调 Dkk1 的表达，激活Wnt/β-catenin信号通路。Mirodenafil 可用于研究勃起功能障碍 (ED)、阿尔茨海默病 (AD) 和系统性硬化症 (SSc)。
| 生物活性 | Mirodenafil (SK3530) is an orally active, potent, reversible, and selectivephosphodiesterase5 (PDE5)inhibitor. Mirodenafil is aglucocorticoid receptor(GR)modulator Mirodenafil activates theWnt/β-cateninsignaling pathway by downregulating Dkk1 expression. Mirodenafil can be used for the research of erectile dysfunction (ED), Alzheimer’s disease (AD) and systemic sclerosis (SSc)[1][2][3]. |
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体外研究
(In Vitro) | Mirodenafil (0-40 μM, 24 h) exerts neuroprotective functions via activating the cGMP/PKG/CREB signaling pathway[2].
Mirodenafil (0-40 μM, 24 h) enhances neuronal survival by protecting the mitochondrial membrane potential and inhibiting apoptosis[2].
Mirodenafil (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 inhibits the transcriptional activity of the glucocorticoid receptor (GR), and inhibits homodimerization of GR in HT-22 cells[2].
Mirodenafil (0-100 μM, 24 h) inhibits TGF-β-induced phosphorylation of Smad2/3 and mRNA expression of the fibrosis marker in fibroblasts[3].
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. Aβ42alone 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. |
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体内研究
(In Vivo) | Mirodenafil (4 mg/kg, IP, daily for 4 weeks) enhances the cognitive-behavioral performance in transgenic AD mice[2].
Mirodenafil (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].
| 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. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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