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sildenafil citrate (Wafesil / Silcap / PheoniX)

✓ Approved

iX Biopharma Ltd · PDE5A · Small Molecule

What is sildenafil citrate?

sildenafil citrate is a small molecule developed by iX Biopharma Ltd. It is approved for therapeutic indications via oral (po) or sublingual (sl)/oral transmucosal.

Drug Profile

Brand NamesWafesil, Silcap, PheoniX
CompanyiX Biopharma Ltd
Drug ClassSmall Molecule
Molecular TargetPDE5A
RouteOral (PO), Sublingual (SL)/Oral Transmucosal
StatusApproved
Sources: ClinicalTrials.gov, iX Biopharma Ltd

Mechanism of Action

Molecular Targets

sildenafil citrate acts on 1 molecular target:

PDE5Aphosphodiesterase 5A (PDE5, CGB-PDE)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

sildenafil citrate is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Reproductive system and breast disordersErectile dysfunction✓ Approved

Related Research Articles

PubMedNature neuroscience2026-10-21

Dysregulated cholesterol trafficking through ABCA1 drives neurodegeneration in Parkinson's disease.

Ma Feng-Xia FX, Zhao Xin-Xin XX, Wang Xiao-Xin XX, Fang Shuo-Yan SY et al.

Although brain cholesterol dysregulation is implicated in Parkinson's disease (PD), targeting cholesterol synthesis has shown limited efficacy. Here we identify ATP-binding cassette transporter A1 (ABCA1) as a critical regulator of cholesterol homeostasis in PD. We show that ABCA1 expression is elevated in the substantia nigra of postmortem PD brains and in a PD mouse model, with regional analyses revealing preferential alterations in nigral and striatal circuits. Mechanistically, astrocytic ABCA1 drives excessive cholesterol efflux in mice, promoting neuronal cholesterol overload. In neurons, ABCA1 localizes to lysosomes, where it facilitates cholesterol import, leading to cholesterol accumulation, autophagy impairment and α-synuclein pathology. Genetic silencing of Abca1 in either astrocytes or dopaminergic neurons attenuates neurodegeneration and behavioral deficits in vivo. Furthermore, we identify magnesium citrate as an ABCA1 inhibitor and show that it reduces dopaminergic neuronal loss in a PD mouse model. Our findings identify an ABCA1-dependent cholesterol pathway underlying PD pathogenesis and support ABCA1 inhibition as a potential disease-modifying strategy.

PMID 42901980
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PubMedBMC genomics2026-10-21

Interactions between kidney proteins and metabolism in Tibetan sheep at different altitudes.

Liu Kejiang K, Zhang Jiang J, Yu Xueqin X, Zhao Pengfei P

When oxygen supply to the kidneys is restricted, it may trigger a series of acid-base imbalances and pathological states, subsequently inducing hypoxic adaptive mechanisms in the kidneys. However, the protein-metabolism interaction mechanisms underlying this process remain unclear. Therefore, this study conducted proteomic and metabolomic analyses on Tibetan sheep kidneys collected at three distinct altitudes (2500 m, 3500 m and 4500 m) to elucidate the protein-metabolism interaction mechanisms during hypoxic adaptation. The results demonstrate a synergistic relationship between proteins and metabolism, revealing dynamic expression patterns. Key DEPs (ALDH2, COX5A, GLUD1, NDUFS2, NDUFS8 and SLC17A1) and key DEMs (Wedelolactone, Cytidine, and 3-hydroxybenzoic acid) primarily participated in the antioxidant defense, anti-inflammatory, and energy supply functions of Tibetan sheep kidney hypoxia adaptation through signaling pathways such as the citrate cycle (TCA cycle) and oxidative phosphorylation. In summary, the adaptive mechanisms to renal hypoxia are not influenced by a single protein or metabolite, but rather are related to the interactions between proteins and metabolites. These interactions may collectively influence the adaptive mechanisms, ensuring that the kidneys maintain normal function in high-altitude environments.

PMID 42902137
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PubMedJournal of contaminant hydrology2026-10-20

Reactive solute transport driven by coupled stress fields affected by injection pressure and permeability during in-situ chemical oxidation remediation of contaminated groundwater.

Xiong Guiyao G, Jiao Zhiyu Z, Zhu Xiaobin X, Zhang Qi Q et al.

Groundwater contamination at the site is worsening, and in-situ chemical oxidation (ISCO) has been widely adopted for contaminated groundwater remediation due to its low environmental risk and low cost. Through laboratory experiments and field simulations, we optimized the system for TCE degradation using activated sodium persulfate and explored how injection pressure and formation permeability affect TCE remediation. The results show that both sodium citrate (TCD) and citrate (CA) chelating agents can increase TCE oxidation by persulfate, with optimal molar ratios of Na2S2O8:TCD:Fe2+:TCE of 20:10:10:1, and Na2S2O8:CA:Fe2+:TCE of 20:5:10:1, achieving high TCE removal rates of 97% and 98%, respectively. Pressurized injection increases the hydraulic gradient and flow velocity, thereby enhancing advection and mechanical dispersion, especially in high-permeability media. In low-permeability media, pressurization also modifies porosity and tortuosity and increases the effective diffusion coefficient, which is relatively more important for solute transport. Pressure-induced permeability changes were limited under the tested 0.1-1 MPa range and were secondary to advection, mechanical dispersion, and effective diffusion. In layered subsurface systems, placing horizontal wells at the interface between high- and low-permeability layers was more effective in delivering oxidants to contaminated regions than vertical wells. In summary, higher-pressure oxidant injection improved remediation in the simulated low-permeability formations by increasing advection, mechanical dispersion, and effective diffusion. The relative contributions were site-specific, and diffusion enhancement was not the sole controlling mechanism. The numerical model can effectively simulate ISCO of TCE by accounting for the multi-field-coupled stress field. It can provide valuable insights for designing groundwater remediation projects.

PMID 42901021
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PubMedEnvironmental science & technology2026-10-20

Phage Lysis Associated with Biodegradable Microplastics Mediates Microbial Physiological Adaptation to Transform Organic Matter in Soil.

Liu Lin L, Hu Long L, Sun He H, Xiao Jiamin J et al.

Biodegradable microplastics (MPs) profoundly impact the storage and stability of soil organic matter (SOM), yet the mechanisms by which phages mediate the transformation of plant- and microbially derived SOM under biodegradable MP perturbation remain poorly understood. This study integrated multiomics, stable isotope techniques, and phage inoculation experiments to investigate how phages mediate SOM transformation following biodegradable MP addition in agricultural soil. The results revealed that lytic phage-bacteria interactions were central to MP-dependent SOM transformation. Polylactic acid (PLA) reduced plant-derived organic molecules by 15% without affecting microbially derived carbon. PLA increased phage lysis and enriched auxiliary metabolic genes (AMGs) such as queC (2.2-fold increase), which supports phage replication and reduces microbial biomass. Pure culture experiments supported that PLA increased phage lytic infectivity. Phage inoculation further revealed that lytic phages accelerated bacteria to shift toward catabolism (e.g., lignocellulose degradation, citrate cycle) in PLA-amended soil, reducing carbon use efficiency (CUE) and accelerating decomposition of plant- and microbially derived carbon through viral shunt. In comparison, polyhydroxyalkanoates (PHA) increased microbially derived molecules by 37%, particularly amino nitrogen compounds. The higher degradability of PHA stimulated lytic phage bloom with their hosts and enriched biosynthesis-related AMGs (e.g., cysH, glmS). Phage inoculation experiments showed that surviving bacteria assimilated phage lysate products into anabolism (e.g., amino acid and amino sugar biosynthesis), enriching metabolites such as l-isoleucine and MurNAc after PHA addition. This increased CUE and accumulation of microbial organics through viral shuttle. These findings uncover phage-mediated mechanisms linking microplastic perturbation to soil carbon cycling.

PMID 42899667
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PubMedFood microbiology2026-10-20

Biosynthetic mechanisms and application of bioactive compounds associated with in vitro lipid-lowering-related activities produced by Lactiplantibacillus plantarum fermentation of Porphyra haitanensis.

Li Zhipeng Z, Qin Yonghong Y, Xu Yating Y, Wang Haoran H et al.

Fourth-harvest Porphyra haitanensis (FPH) is abundant but underutilized because of undesirable flavor and poor palatability. Microbial fermentation is an effective strategy for the high-value utilization of FPH. The metabolic basis and application potential of bioactive compounds accumulated during FPH fermentation by Lactiplantibacillus plantarum and associated with in vitro lipid digestion and absorption inhibitory activities were investigated. The results demonstrated that fermentation increased the maximal inhibition rates of pancreatic lipase, cholesterol esterase, and cholesterol micellar solubility to 68.27 ± 0.81%, 68.97 ± 0.61%, and 72.72 ± 0.52%, respectively, and increased glycocholate and taurocholate binding to 53.79 ± 0.74% and 55.91 ± 1.45%, respectively. Metabolomics showed extensive metabolic remodeling and suggested γ-aminobutyric acid (GABA) and p-coumaric acid (pCA) as putative candidate metabolites associated with the enhanced in vitro lipid-lowering-related activities and flavor quality. KEGG analysis indicated that the accumulation of GABA and pCA may be related to glutamate metabolism, substrate degradation, and associated enzyme-catalyzed pathways, providing a potential metabolic explanation rather than direct evidence of biosynthetic mechanisms. A fermented FPH beverage was subsequently formulated, and the optimal formulation consisted of 70% fermented liquor, 10 g/100 mL erythritol, and 0.5 g/100 mL sodium citrate. The formulated beverage was further subjected to pasteurization, and 90 °C for 10 min was selected as the final processing condition for the subsequent storage evaluation. This treatment maintained a high level of in vitro lipid-lowering-related activity, with a pancreatic lipase inhibition rate of 93.02 ± 1.75%, while providing better physical stability. The shelf life was predicted to be 46 days at 20 °C and 308 days at 4 °C based on the storage stability model. This study provides a theoretical basis and technical support for the high-value utilization of low-quality seaweed.

PMID 42901657
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PubMedBJU international2026-10-20

Does bespoke metabolic investigation reduce urinary stone recurrence? A narrative review.

Wiseman Oliver J OJ, Turney Ben W BW

To examine whether individualised ('bespoke') metabolic investigation and targeted dietary and medical therapy reduces urinary stone recurrence, and whether the approach also improves health-related quality of life (HRQOL) and lowers financial and environmental cost. In this narrative review we searched PubMed/Medical Literature Analysis and Retrieval System Online (MEDLINE), the Cochrane Library and Europe PubMed Central (PMC) (January 1980 to March 2026) for randomised trials, controlled cohorts and systematic reviews on metabolic assessment and stone recurrence prevention in adults, supplemented by European Association of Urology (EAU), American Urological Association (AUA), National Institute for Health and Care Excellence (NICE) and American College of Physicians (ACP) guidance and by hand-searching of reference lists. Interventions that correct a defined urinary abnormality each reduce stone recurrence. Increased fluid intake approximately halves it (relative risk [RR] 0.45-0.55); a normal calcium, reduced sodium, reduced animal protein diet achieves a similar reduction in hypercalciuric calcium-oxalate formers (RR 0.49); and targeted pharmacotherapy lowers it further (potassium citrate RR approximately 0.25, thiazides 0.52, allopurinol 0.59), although the rigorous NOSTONE trial (ClinicalTrials.gov identifier: NCT03057431) found no significant thiazide benefit. After shockwave lithotripsy and percutaneous nephrolithotomy, medical therapy reduces stone formation and residual-fragment regrowth. Evidence that 24-h-urine-directed therapy outperforms empirical therapy is confined to high-risk patients, in whom selective treatment yields significantly fewer stone-related events. Stone disease impairs disease-specific quality of life and is costly, so preventing stone recurrence is cost-saving. The case for bespoke prevention is strongest in recurrent, high-risk and post-procedural stone formers. Identifying the abnormality, correcting it, ensuring adherence and confirming the response by repeat testing offers the best chance to reduce stone recurrence and residual-stone growth, improve HRQOL, and lower financial cost.

PMID 42901875
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