Mirodenafil(CAS:862189-95-5)

Mirodenafil (SK3530, CAS 862189-95-5) was originally discovered by SK Chemicals of South Korea, a second-generation structurally optimized selective PDE5 inhibitor covering two major R&D verticals: clinical formulations for erectile dysfunction and novel neuroprotective agents for Alzheimer’s disease. Endowed with ultra-high target specificity and unique blood-brain barrier penetration capacity, it has become an indispensable core research API for universities, CRO laboratories and innovative pharmaceutical enterprises investigating urological disorders, neurodegeneration and fibrosis pathogenesis. With molecular formula C₂₄H₃₀N₆O₄S and molecular weight 506.61, it exists as white crystalline powder freely soluble in DMSO, methanol and ethanol with low aqueous solubility. It maintains outstanding long-term stability under light-shielded sealed ambient storage, with HPLC purity consistently above 99.5%. Strict specifications control process related impurities, heavy metals and residual solvents fully comply with research reagent and generic drug raw material standards, fully supporting full-range research workflows including in vitro PDE enzyme activity screening, cavernous smooth muscle cell assays, AD transgenic mouse modeling and cerebral microcirculation detection, delivering uniform batch bioactivity and highly repeatable experimental data.

In terms of dual core pharmacological mechanisms, conventional PDE5 inhibitors such as sildenafil and vardenafil suffer from off-target PDE6 binding causing ocular adverse reactions and poor brain penetration, drawbacks resolved via benzenesulfonamide side chain modification in Mirodenafil. Peripheral urological pathway: it reversibly occupies the catalytic pocket of PDE5 with an ultra-low IC50 of 0.34 nM, blocking intracellular cGMP degradation in penile corpus cavernosum smooth muscle, elevating cytoplasmic cGMP concentration to relax vascular smooth muscle and boost arterial inflow. Oral doses of 50 mg and 100 mg deliver stable therapeutic improvement for both organic and psychogenic erectile dysfunction with moderate onset window and lower incidence of cardiovascular side effects. Its differentiated core advantage lies in central neuroprotective activity: balanced lipophilic-hydrophilic properties enable efficient blood-brain barrier penetration. Once inside the brain, it activates the neuronal cGMP/PKG/CREB signaling cascade to trigger three synergistic neuroprotective effects: boosting autophagy to accelerate degradation and clearance of toxic Aβ42 amyloid plaques; inhibiting GSK-3β kinase to reduce pathological Tau hyperphosphorylation and neurofibrillary tangles; downregulating central pro-inflammatory cytokines including IL-1β and TNF-α to alleviate neuroinflammation induced by overactivated microglia. In vitro cellular assays verify its capacity to suppress neuronal apoptosis and stimulate synaptic regeneration, while Phase 2 clinical data confirmed significant reduction of cerebrospinal fluid pTau-181 biomarker and steady improvement in cognitive assessment scores.

Its clinical and scientific research applications cover three core verticals. Firstly, andrological pharmacological research: as the gold-standard positive control for ED studies, it is deployed in efficacy evaluation of animal models with spinal cord injury or diabetes-associated erectile dysfunction, comparing onset duration and cardiovascular safety windows across different PDE5 inhibitors. Secondly, innovative drug development for Alzheimer’s disease: the global Phase 3 POLARIS-AD trial of AR1001 enrolls subjects across China, the US and Europe, making Mirodenafil one of the rare small molecules integrating cerebral vasodilation, amyloid clearance and neurofibrillary tangle suppression, widely adopted for AD pathway dissection and multi-target neuroprotective lead compound screening. Thirdly, extended fibrosis research: it suppresses the TGF-β/Smad fibrotic cascade and reduces collagen secretion from fibroblasts, supporting mechanistic exploration of systemic sclerosis and renal fibrosis, as well as combined administration assays for comorbidities of cerebral microcirculation dysfunction and cognitive decline.

Regarding raw material supply and industrial research value, Mirodenafil adopts mature total synthetic routes with refined purification procedures for benzenesulfonamide side chain coupling to efficiently remove stereoisomers and process impurities. Complete specifications ranging from milligram to kilogram scale meet all demands from microscale high-throughput screening to large-scale long-term in vivo efficacy studies. It exhibits favorable oral administration tolerance without severe hypotension or visual damage under routine doses, providing a wide safe experimental window suitable for multi-month chronic intervention on AD animal models. With global aging population expansion and growing patient pools of erectile dysfunction and mild Alzheimer’s disease, PDE5 derivatives with dual urological and neuroprotective activity have become a hot frontier for innovative drug R&D. Supported by comprehensive Phase 1/2/3 human clinical datasets and abundant published in vitro & in vivo literature, Mirodenafil maintains irreplaceable rigid research and commercial value in andrological pharmaceutics, neurodegenerative disease pharmacology and multi-target small-molecule drug development, promising stable and broad long-term R&D prospects across the global pharmaceutical research industry.