Mirodenafil
(Synonyms: 米罗那非; SK3530) 目录号 : GC36616
A PDE5 inhibitor
Cas No.:862189-95-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Mirodenafil is a phosphodiesterase 5 (PDE5) inhibitor.1 It increases penile intracavernosal pressure (ICP) in a rat model of diabetes induced by streptozotocin and in a rat model of cavernosal nerve injury when administered at doses of 1 and 10 mg/kg, respectively.1,2 Mirodenafil (4 mg/kg per day) decreases bladder wall submucosal fibrosis and degeneration in a rat model of chronic bladder ischemia.3 It also decreases bladder overactivity in a female rat model of partial bladder outlet obstruction.4
1.Park, K., Cho, S.Y., and Kim, S.W.Erectile response to type 5 phosphodiesterase inhibitor could be preserved with the addition of simvastatin to conventional insulin treatment in rat model of diabetesInt. J. Androl.34(5 Pt 2)e468-e474(2011) 2.Kim, H., Sohn, D.W., Kim, S.D., et al.The effect of mirodenafil on the penile erection and corpus cavernosum in the rat model of cavernosal nerve injuryInt. J. Impot. Res.22(5)291-297(2010) 3.Choi, H., Bae, J.H., Shim, J.S., et al.Mirodenafil prevents bladder dysfunction induced by chronic bladder ischemia in ratsInt. Neurourol. J.19(1)19-26(2015) 4.Kang, J.Y., Kim, E.K., and Kim, K.M.Effects of mirodenafil, a phosphodiesterase-5 inhibitor, on female rat bladder in a partial bladder outlet obstruction model: Physiological and immunohistochemical aspectsKorean J. Urol.54(5)339-344(2013)
| Cas No. | 862189-95-5 | SDF | |
| 别名 | 米罗那非; SK3530 | ||
| Canonical SMILES | O=C1C(N(CC)C=C2CCC)=C2N=C(C3=CC(S(=O)(N4CCN(CCO)CC4)=O)=CC=C3OCCC)N1 | ||
| 分子式 | C26H37N5O5S | 分子量 | 531.67 |
| 溶解度 | DMSO : 125 mg/mL (235.11 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 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°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Mirodenafil for the treatment of erectile dysfunction: a systematic review of the literature
World J Mens Health 2014 Apr;32(1):18-27.PMID:24872948DOI:10.5534/wjmh.2014.32.1.18.
Phosphodiesterase type 5 (PDE5) inhibitors are the most commonly used treatment for erectile dysfunction (ED). Since the launch of sildenafil, several drugs-including Mirodenafil, sildenafil citrate (sildenafil), tadalafil, vardenafil HCL (vardenafil), udenafil, and avanafil-have become available. Mirodenafil is a newly developed pyrrolopyrimidinone compound, which is a potent, reversible, and selective oral PDE5 inhibitor. Mirodenafil was launched in Korea in 2007, and an orally disintegrating film of Mirodenafil was developed in 2011 for benefitting patients having difficulty in swallowing tablets. This study aimed to review the pharmacokinetic characteristic profile of Mirodenafil and report evidence on its efficacy in the case of ED. In addition, we reviewed randomized controlled studies of Mirodenafil's daily administration and efficacy for lower urinary tract symptoms.
Mirodenafil ameliorates skin fibrosis in bleomycin-induced mouse model of systemic sclerosis
Anim Cells Syst (Seoul) 2021 Nov 3;25(6):387-395.PMID:35059138DOI:10.1080/19768354.2021.1995486.
Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by fibrosis of the skin and internal organs. Despite the recent advances in the pathogenesis and treatment of SSc, effective therapies for fibrosis caused by SSc have not yet been established. In this study, we investigated the potential role of Mirodenafil, a potent phosphodiesterase 5 (PDE5) inhibitor, in the treatment of fibrosis in SSc. We used a bleomycin (BLM)-induced SSc mouse model to mimic the typical features of fibrosis in human SSc and examined the dermal thickness to assess the degree of skin fibrosis after staining with hematoxylin and eosin or Masson's trichrome stains. The effect of Mirodenafil on the expression of profibrotic genes was also analyzed by treating fibroblasts with transforming growth factor (TGF)-β and Mirodenafil. We showed that Mirodenafil ameliorated dermal fibrosis and downregulated the protein levels of fibrosis markers including COL1A1 and α-SMA in the BLM-induced SSc mouse model. Further, using mouse embryonic fibroblasts and human lung fibroblasts, we demonstrated that the expression of collagen and profibrotic genes was reduced by treatment with Mirodenafil. Finally, we showed that Mirodenafil inhibited TGF-β-induced phosphorylation of Smad2/3 in fibroblasts, which suggested that this drug may ameliorate fibrosis by suppressing the TGF-β/Smad signaling pathway. Our findings suggest that Mirodenafil possesses a therapeutic potential for treating fibrosis in SSc.
Phosphodiesterase 5 inhibitor Mirodenafil ameliorates Alzheimer-like pathology and symptoms by multimodal actions
Alzheimers Res Ther 2022 Jul 8;14(1):92.PMID:35804462DOI:10.1186/s13195-022-01034-3.
Background: Alzheimer's disease (AD) pathology is associated with complex interactions among multiple factors, involving an intertwined network of various signaling pathways. The polypharmacological approach is an emerging therapeutic strategy that has been proposed to overcome the multifactorial nature of AD by targeting multiple pathophysiological factors including amyloid-β (Aβ) and phosphorylated tau. We evaluated a blood-brain barrier penetrating phosphodiesterase 5 (PDE5) inhibitor, Mirodenafil (5-ethyl-2-7-n-propyl-3,5-dihydrro-4H-pyrrolo[3,2-d]pyrimidin-4-one), for its therapeutic effects on AD with polypharmacological properties. Methods: To evaluate the potential of Mirodenafil as a disease-modifying AD agent, Mirodenafil was administered to test its effects on the cognitive behaviors of the APP-C105 AD mouse model using the Morris water maze and passive avoidance tests. To investigate the mechanisms of action that underlie the beneficial disease-modifying effects of Mirodenafil, human neuroblastoma SH-SY5Y cells and mouse hippocampal HT-22 cells were used to show mirodenafil-induced alterations associated with the cyclic guanosine monophosphate (cGMP)/cGMP-dependent protein kinase (PKG)/cAMP-responsive element-binding protein (CREB) pathway, apoptotic cell death, tau phosphorylation, amyloidogenesis, the autophagy-lysosome pathway, glucocorticoid receptor (GR) transcriptional activity, and the Wnt/β-catenin signaling. Results: Here, Mirodenafil is demonstrated to improve cognitive behavior in the APP-C105 mouse model. Mirodenafil not only reduced the Aβ and phosphorylated tau burdens in vivo, but also ameliorated AD pathology induced by Aβ through the modulation of the cGMP/PKG/CREB signaling pathway, glycogen synthase kinase 3β (GSK-3β) activity, GR transcriptional activity, and the Wnt/β-catenin signaling in neuronal cells. Interestingly, homodimerization and nuclear localization of GR were inhibited by Mirodenafil, but not by other PDE5 inhibitors. In addition, only Mirodenafil reduced the expression levels of the Wnt antagonist Dickkopf-1 (Dkk-1), thus activating the Wnt/β-catenin signaling. Conclusions: These findings strongly suggest that the PDE5 inhibitor Mirodenafil shows promise as a potential polypharmacological drug candidate for AD treatment, acting on multiple key signaling pathways involved in amyloid deposition, phosphorylated tau burden, the cGMP/PKG/CREB pathway, GSK-3β kinase activity, GR signaling, and the Wnt/β-catenin signaling. Mirodenafil administration to the APP-C105 AD mouse model also improved cognitive behavior, demonstrating the potential of Mirodenafil as a polypharmacological AD therapeutic agent.
A review of the efficacy and safety of Mirodenafil in the management of erectile dysfunction
Ther Adv Urol 2016 Apr;8(2):100-17.PMID:27034723DOI:10.1177/1756287215625408.
Erectile dysfunction (ED) is a common disorder that can jeopardize quality of life and the partnership of patients and their sexual partners. The advent of oral phosphodiesterase type 5 inhibitors (PDE5Is) has revolutionized a treatment for ED, and they are recognized as the first-line therapy for ED, regardless of its etiology. Mirodenafil, a second-generation PDE5I, has biochemical profiles such as high affinity for PDE5 and high selectivity for PDE5 over other PDE isoforms, compared to other existing PDE5Is such as sildenafil, vardenafil and tadalafil. Available evidence has suggested that doses of 50 and 100 mg Mirodenafil effectively improve ED [with improvements in the erectile function domain of the International Index of Erectile Function (IIEF-EF) scores, positive responses to questions 2 of the Sexual Encounter Profiles (SEP2) and questions 3 of the Sexual Encounter Profiles (SEP3): 7.6-11.6 points, 27.72-38.98% and 44.20-67.33%, respectively] in a broad range of patient populations with ED of a variety of underlying etiologies, severities and ages, without any serious treatment-related adverse effects. In the treatment of diabetic ED, a traditionally difficult-to-treat population, 100 mg Mirodenafil has been reported to offer favorable efficacy (with improvements in the IIEF-EF scores, and positive responses to the SEP2 and the SEP3: 9.3 points, 36.1% and 61.8%, respectively) and tolerability (mild adverse effects of less than 19.6%), which are comparable with results from clinical studies on other PDE5Is. Mirodenafil appears to be effective, safe and well tolerated in men with both ED and hypertension or lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH) who are taking concomitant antihypertensive medications or α1-blockers. Furthermore, recent evidence has indicated that Mirodenafil may be a potential option for chronic dosing in the treatment of ED despite its short half-life (T 1/2). Most of the available clinical studies have reported that adverse effects (up to 53.7%) caused by 50 and 100 mg Mirodenafil are mild or moderate in severity, with headache (1.8-14.8%) and flushing (6.7-24.1%) being the most common. Due to the pharmacodynamic profiles of Mirodenafil, its tolerability is expected to be somewhat better than those of the other PDE5Is. However, further well designed studies with larger cohorts of different ethnicities, flexible dosing schedules and long-term follow up are necessary to confirm the favorable efficacy and tolerability profiles of Mirodenafil for the treatment of ED.
Mirodenafil prevents bladder dysfunction induced by chronic bladder ischemia in rats
Int Neurourol J 2015 Mar;19(1):19-26.PMID:25833477DOI:10.5213/inj.2015.19.1.19.
Purpose: To investigate the protective effect of Mirodenafil on bladder function in a rat model of chronic bladder ischemia (CBI). Methods: Twenty-four Sprague-Dawley rats were randomized to three groups: untreated, sham-operated rats (control group); untreated, CBI model rats (CBI group); and CBI rats treated daily with 4 mg/kg Mirodenafil (CBI+Mirodenafil group). The CBI and CBI+Mirodenafil groups underwent endothelial injury to the iliac arteries and were fed a 2% cholesterol diet after injury. Four weeks after surgery, the CBI+Mirodenafil group started daily treatment with Mirodenafil for four weeks. Eight weeks after surgery, continuous in vivo cystometry and in vivo organ bath studies of detrusor muscle strips were performed. Results: in vivo cystometry revealed that the rats in the CBI group had a significantly higher micturition frequency, lower bladder capacity, and lower compliance than the rats in the control and CBI+Mirodenafil groups. The detrusor muscle strip study showed that the magnitude of the carbachol-induced contractile response was significantly lower in the CBI group compared to either the control or CBI+Mirodenafil group. Addition of daily Mirodenafil after induction of CBI decreased the contractile response, compared to untreated CBI rats. CBI induced submucosal fibrosis and degenerative changes in bladder walls, which was reversed by the addition of Mirodenafil. Conclusions: Daily treatment with Mirodenafil showed protective effects against bladder dysfunction resulting from CBI in rats.