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UR

urokinase (Breokinase / Alphakinase / Thrombolase)

✓ Approved

Mitsubishi Tanabe Pharma Corporation · PLAU

What is urokinase?

urokinase is a therapeutic agent developed by Mitsubishi Tanabe Pharma Corporation. It is approved for therapeutic indications.

Drug Profile

Brand NamesBreokinase, Alphakinase, Thrombolase
CompanyMitsubishi Tanabe Pharma Corporation
Molecular TargetPLAU
StatusApproved
Sources: ClinicalTrials.gov, Mitsubishi Tanabe Pharma Corporation

Mechanism of Action

Molecular Targets

urokinase acts on 1 molecular target:

PLAUplasminogen activator, urokinase (URK, UPA)
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Therapeutic Indications

urokinase is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Respiratory, thoracic and mediastinal disordersPulmonary thrombosis✓ Approved

Related Research Articles

PubMedThrombosis research2026-08-28

Plasma kallikrein in breast cancer cells: Interactions with urokinase plasminogen activator system and syndecans.

Shimon Samara M M SMM, Meneghetti Maria Cecília Z MCZ, Bromberg Natalia N, Cavalheiro Renan P RP et al.

During invasive migration, cancer cells use secreted proteases to remove various extracellular matrix components. The urokinase plasminogen activator (uPA) and its receptor (uPAR), together with kallikreins, perform key functions in this proteolytic network through control of various proteases. Plasma kallikrein (PKa) is an important activator of pro-uPA on the cell surface. To examine the role of plasma kallikrein in malignancy, with a particular focus on breast cancer. The MCF-7 (non-metastatic) and MDA-MB-231 (metastatic) breast cancer cell lines were analyzed using immunodetection, PCR, and various enzyme activity and cell dynamics assays. Relative mRNA expression of plasma prekallikrein (PK) was detected in both MCF-7 cells and MDA-MB-231 cells. In addition, in both cell types, PK/PKa was found either on the cell surface or inside cells. In MCF-7 cells, fragments of the PKa active site were found in lysates, whereas in MDA-MB-231 cells, PKa was found most inside lysosomes. PKa colocalized better with syndecan-1 (syn-1) on the surface but with syn-4 in cytoplasm. Both cell lines showed activity of either uPA or PKa, but the small increase in PKa activity after treatment with PKa inhibitor PKSI (or with 4-Cl in MDA-MB-231 cells) suggested regulation of PKa on the cell surface by proteolysis. Our results suggest that PKa has roles in migration, uPAR cleavage, and pro-uPA activation and can be controlled by proteolysis and endocytosis, and that syndecans may function as receptors for these proteins, suggesting a role in recycling processes.

PMID 42664681
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PubMedInternational journal of molecular sciences2026-08-27

Novel Roles of Urokinase- and Tissue-Type Plasminogen Activators in Substance Use Disorders: A Narrative Review of Molecular Mechanisms and Translational Perspectives.

Bahi Amine A, Steele Sinclair S

The plasminogen activator system (PAS), comprising urokinase-type plasminogen activator (uPA), tissue-type plasminogen activator (tPA), their receptors, and endogenous inhibitors, has been extensively investigated for its established roles in haemostasis, fibrinolysis, vascular remodelling and extracellular matrix (ECM) homeostasis. Increasing evidence indicates that the functions of the PAS extend well beyond the cardiovascular system and have important regulatory roles in neuronal plasticity, synaptic remodelling, neuroinflammation, and neurotrophic signalling. These processes are increasingly recognized as central contributors to the neurobiological adaptations underlying substance use disorders (SUDs). In this narrative review, we critically evaluate the current evidence regarding the involvement of the PAS in SUDs, with particular emphasis on the molecular and cellular mechanisms through which uPA and tPA influence addiction-related neuroplasticity. The available literature is predominantly derived from preclinical studies, while direct clinical evidence remains limited. Experimental findings support roles for uPA and tPA in modulating reward-related circuitry, behavioural sensitization, relapse-like behaviours, and neurotrophic signalling, including potential interactions with brain-derived neurotrophic factor (BDNF)-related pathways, although the relative contributions of plasmin-dependent and plasmin-independent pathways remain incompletely understood. We also discuss the potential involvement of the PAS in neuroinflammatory responses and synaptic remodelling, together with the challenges associated with translating these findings into clinically relevant biomarkers or therapeutic strategies. Finally, we identify important gaps in current knowledge, including the need for independent replication, mechanistic clarification, and well-designed human studies to establish the clinical relevance of PAS dysregulation in addiction. Collectively, the available evidence supports a modulatory role for the PAS in addiction-related neurobiology and provides a rationale for further translational investigation, while highlighting that PAS-directed therapeutic approaches remain experimental and require substantial preclinical and clinical validation.

PMID 42653404
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PubMedPharmaceutics2026-08-27

Dual-Functional Self-Assembled Nanoparticles for Synergistic Photodynamic Therapy and Antimetastatic Treatment of Colorectal Cancer.

Li Yixuan Y, Zhang Haokun H, Xu Tinghai T, Jiang Ruifeng R et al.

Background: Colorectal cancer (CRC) is a major clinical challenge due to high metastasis and therapy resistance. Photodynamic therapy (PDT) offers precise tumor ablation but lacks sustained anti-metastatic activity. Peptidic urokinase-type plasminogen activator (uPA) inhibitors suppress metastasis but suffer from short half-life and poor tumor retention. This study aimed to develop a dual-functional self-assembled nanoplatform integrating PDT and selective uPA inhibition for synergistic CRC treatment. Methods: We designed and synthesized a conjugate by linking pyropheophorbide-a (PPA) with uPA-targeted cyclic peptide IG2, which self-assembled into nanoparticles (PINPs). Physicochemical properties, reactive oxygen species (ROS) generation, and uPA inhibitory activity were characterized. In vitro studies included cellular uptake, cytotoxicity, and invasion assays. In vivo therapeutic efficacy was evaluated in subcutaneous CT26 tumor models and lung metastasis models, with biosafety assessed by body weight monitoring. Results: PINPs exhibited uniform spherical nanostructure, prolonged blood circulation, and enhanced tumor accumulation via the enhanced permeability and retention (EPR) effect. Under 680 nm irradiation, PINPs generated robust ROS and induced tumor cell apoptosis. PINPs potently inhibited uPA activity and suppressed tumor cell invasion. In vivo, PINPs plus PDT achieved significant tumor growth inhibition (73.6%) and strong anti-metastatic efficacy (60.7%), superior to free IG2. No obvious systemic toxicity was observed. Conclusions: The dual-functional PINPs achieve short-term acute tumor ablation via PDT and sustained anti-metastatic potential via uPA inhibition within the tested observation windows, with favorable biosafety. This carrier-free self-assembly strategy provides proof-of-concept validation and a generalizable design paradigm for developing synergistic anti-metastatic nanotherapeutics against metastatic CRC.

PMID 42654065
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PubMedEClinicalMedicine2026-08-27

Nurse-led hospital violence intervention programme versus standard care in Wales: a cost-effectiveness analysis.

Premji Shainur S, Moore Simon C SC, Tod Daniel D, Hamilton Megan M et al.

Violence is a major public health issue. In the United Kingdom (UK), injuries resulting from interpersonal violence were estimated to cost the National Health Service (NHS) £2.9 billion annually. Hospital Violence Intervention Programmes (HVIPs), based in Emergency Departments (EDs), identify individuals (both perpetrators and victims) who may benefit from support for modifiable risk factors associated with exposure to violence. In this study we evaluate the cost-effectiveness of implementing an HVIP called the Violence Prevention Team (VPT) relative to standard care in Wales. We conducted a cost-effectiveness analysis of VPTs in ED relative to standard care. We included patients aged 11 years or older who attended ED with an assault-related injury between November 2019 and February 2024 in Wales. Participants exposed to the VPT or standard care were matched with a minimum 1:1 ratio. A hybrid decision tree-Markov model was created to follow patients attending ED for an initial assault-related attendance and to track any subsequent unplanned ED visits thereafter. Health outcomes were measured in quality-adjusted life years (QALYs), and costs (in 2023/2024 British pounds sterling) were estimated using a (a) health perspective and (b) societal perspective (including additional costs across the third sector) over a time horizon of 10 years. Routine data from the Secure Anonymised Information Linkage (SAIL) databank were used to inform model probability and healthcare cost estimates. QALYs were estimated using the literature. We estimated the incremental cost-effectiveness ratio (ICER), net monetary and net health benefits, and probability of being cost-decreasing and QALY-increasing. ICERs were interpreted against the UK Department for Health's cost effectiveness threshold of £15,000 per QALY and the National Institute for Health and Care Excellence (NICE) cost-effectiveness threshold of £20,000-£30,000 per QALY. This study is registered with ISRCTN (68945844). Our base case analysis suggested that implementing VPTs in ED was cost-saving and more effective relative to standard care, from both a health and societal perspective. At a NICE cost-effectiveness threshold of £20,000-£30,000 per QALY, there was 83% probability that VPTs in ED are considered cost-effective relative to standard care. At a threshold of £15,000 per QALY, the probability that VPTs in ED are considered cost-effective relative to standard care was 84%. When only including ED and associated inpatient admission costs and excluding primary care visit costs, VPTs remained cost-effective from a health perspective (£12,950 per QALY gained). VPTs in ED are strategically placed to intervene following injuries. They have the potential to reduce costs and improve health outcomes, and their implementation should be prioritised by the NHS. This study was funded by the National Institute for Health and Care Research, Public Health Research Board (NIHR134055).

PMID 42656807
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PubMedPharmaceuticals (Basel, Switzerland)2026-08-27

Intrapleural Fibrinolytic Therapy in the Management of Pediatric Pleural Empyema: A Narrative Review.

Esposito Susanna S, Fainardi Valentina V, Arnesano Gaia Giorgia GG, Principi Nicola N

Background: Pediatric pleural empyema is a major complication of community-acquired pneumonia and remains associated with substantial morbidity despite advances in vaccination, antimicrobial therapy, and supportive care. Intrapleural fibrinolytic therapy has become an important minimally invasive treatment for complicated parapneumonic effusions and empyema, but uncertainty persists regarding the optimal fibrinolytic agent, treatment protocols, patient selection, and indications for surgical intervention. Methods: A narrative review of the literature was conducted to summarize current evidence on the use of intrapleural fibrinolytic therapy in pediatric pleural empyema. Experimental studies, randomized controlled trials, observational studies, systematic reviews, meta-analyses, and international clinical practice guidelines were critically reviewed. Particular attention was paid to the biological rationale for fibrinolysis, pharmacological characteristics of available agents, comparative effectiveness with video-assisted thoracoscopic surgery (VATS), practical treatment protocols, safety, and future research priorities. Results: Intrapleural fibrinolysis effectively improves pleural drainage by lysing fibrin septations during the fibrinopurulent stage of empyema and is associated with shorter hospitalization compared with chest-tube drainage alone. Urokinase remains the fibrinolytic agent supported by the highest-quality pediatric randomized evidence, whereas alteplase has demonstrated favorable outcomes in observational studies and randomized comparisons with VATS. Current evidence indicates comparable clinical outcomes between fibrinolysis and primary VATS in appropriately selected children, although fibrinolysis is generally associated with lower treatment costs and avoidance of surgery in most patients. Conventional-dose fibrinolytic therapy has an acceptable safety profile, with clinically significant bleeding reported only rarely. Current pediatric evidence does not support the routine addition of DNase to tissue plasminogen activator. Conclusions: Intrapleural fibrinolytic therapy represents a safe, effective, and minimally invasive first-line treatment for most children with complicated parapneumonic effusions and pleural empyema requiring drainage. Management should be individualized within a multidisciplinary framework, integrating timely diagnosis, image-guided pleural drainage, appropriate antimicrobial therapy, and selective surgical intervention. Future multicenter studies are needed to optimize fibrinolytic protocols, validate predictive biomarkers, and further standardize clinical management.

PMID 42653704
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PubMedProteomes2026-08-26

Proteomic Mediators Linking Autoimmune Diseases to Major Adverse Cardiovascular Events: Insights from the UK Biobank.

Huang Jingwen J, Liu Chang C, Sperling Laurence S LS, Quyyumi Arshed A AA et al.

Autoimmune diseases (AIDs) are associated with increased cardiovascular risk. However, specific protein mediators linking AIDs to major adverse cardiovascular events (MACE) and cardiovascular death (CV death) remain unexplored. This study identifies proteomic mediators linking AIDs to MACE via high-dimensional mediation analysis in the UK Biobank. We used UK Biobank data with proteomic profiling by Olink platform. Participants with prevalent myocardial infarction (MI), stroke, and heart failure at baseline were excluded. AIDs were categorized into musculoskeletal (MSK), vasculitis, gastrointestinal (GI), neurologic, and rheumatic fever subsets. Fine-Gray models assessed associations between AIDs and MACE and CV death. Proteome-wide association studies identified proteins associated with both AIDs and cardiovascular outcomes. High-dimensional mediation analysis (HIMA) explored protein-mediated pathways. All models adjusted for age, sex, lipids, BMI, smoking, hypertension, diabetes, chronic kidney disease, atrial fibrillation, and coronary artery disease. Among 400,633 participants (median follow-up 14.5 years, 44.8% male), AIDs were present in 28,754 (7.2%). All AID categories were associated with increased MACE (sHR: MSK 1.34, vasculitis 1.67, GI 1.20, neurologic 1.33, rheumatic fever 1.38; all p < 0.001). For CV death, MSK, vasculitis, and rheumatic fever showed increased risk (sHR 1.34, 1.78, 1.51; all p ≤ 0.004), but not GI or neurologic AIDs. In 43,599 participants with proteomic data, HIMA identified 66 and 32 unique potential mediators linking AIDs to MACE and CV death, respectively. Four proteins (Growth Differentiation Factor 15, Interleukin-15, urokinase plasminogen activator receptor, and Tenascin C) mediated the AID-MACE relationship across multiple AID categories. Growth Differentiation Factor 15 and Interleukin-15 were shared mediators for CV death. This proteomic analysis identifies specific proteins that may mediate the association between AIDs and adverse cardiovascular outcomes, offering mechanistic insights into immune-related cardiovascular risk. These findings are hypothesis-generating and require replication and validation before the identified proteins can be considered causal mediators or adopted for clinical risk stratification.

PMID 42647374
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