Mirodenafil (SK3530) dihydrochloride 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 dihydrochloride 是一种糖皮质激素受体 (GR) 的调节剂。Mirodenafil dihydrochloride 通过下调 Dkk1 的表达，激活Wnt/β-catenin信号通路。Mirodenafil dihydrochloride 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) dihydrochloride is an orally active, potent, reversible, and selectivephosphodiesterase5 (PDE5)inhibitor. Mirodenafil dihydrochloride is aglucocorticoid receptor(GR)modulator Mirodenafil dihydrochloride activates theWnt/β-cateninsignaling 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]. |
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体外研究
(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].
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 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].
| 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 | 4°C, stored under nitrogen *In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen) |
| 溶解性数据 | In Vitro: DMSO : ≥ 100 mg/mL(165.40 mM) H2O : 5 mg/mL(8.27 mM;ultrasonic and warming and heat to 60℃) *"≥" means soluble, but saturation unknown. 配制储备液 | 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 |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month (stored under nitrogen)。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.5 mg/mL (4.14 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (4.14 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.5 mg/mL (4.14 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (4.14 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 3. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (4.14 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (4.14 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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