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urokinase

✓ Approved

Bharat Serums and Vaccines Limited · FSHR · Small Molecule

What is urokinase?

urokinase is a small molecule developed by Bharat Serums and Vaccines Limited. It is approved for therapeutic indications via injectable (others) or intravenous (iv).

Drug Profile

CompanyBharat Serums and Vaccines Limited
Drug ClassSmall Molecule, Polyclonal Antibodies, Recombinant Proteins, Polypeptide, Antibody
Molecular TargetFSHR, LHCGR, PLAU, PLG
RouteInjectable (Others), Intravenous (IV)
StatusApproved
Sources: ClinicalTrials.gov, Bharat Serums and Vaccines Limited

Mechanism of Action

Molecular Targets

urokinase acts on 4 molecular targets:

FSHRfollicle stimulating hormone receptor (FSHRO, ODG1)
LHCGRluteinizing hormone/choriogonadotropin receptor (ULG5, LH/CGR)
PLAUplasminogen activator, urokinase (URK, UPA)
PLGplasminogen (HAE4)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

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

Therapeutic AreaConditionPhase
Vascular disordersThrombosis✓ 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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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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PubMedEuropean journal of medicinal chemistry2026-08-24

Critical structural insights into selective small-molecule and peptide inhibitors of human urokinase-type plasminogen activator.

Pluskota-Karwatka Donata D, Wawrzyniak Dariusz D, Nowicki Jakub J, Jaworska Klaudia K et al.

Human urokinase-type plasminogen activator (uPA) is a trypsin-like serine protease that plays a crucial role in plasminogen activation and extracellular matrix (ECM) remodelling. Dysregulation of the interactions of uPA with its receptor (uPAR) has been strongly associated with tumour invasion, metastasis, angiogenesis, inflammation and tissue remodelling, making uPA a very promising therapeutic target. Overexpression of uPA in tumours compared to healthy tissue is significantly associated with worse clinicopathological features and poorer patient survival in many types of cancer. Despite the biological significance of uPA, the development of selective inhibitors remains challenging due to the high structural similarity of the conserved proteolytic domain of the serine protease family. This review summarises advances in the field of human uPA inhibition, with a particular emphasis on structural insight that underpin the design of selective small-molecule and peptide-based inhibitors. We discuss the three-dimensional structure of the uPA catalytic domain and the properties of the binding site that can be exploited to enhance inhibitor specificity. The primary focus is on structure-activity relationships (SAR) and crystallographic studies, which have contributed to the development of compounds targeting uPA. The ADME (Absorption, Distribution, Metabolism, and Excretion) and drug-likeness analysis revealed that many potent uPA inhibitors possess pharmacokinetic limitations, including poor gastrointestinal absorption, high polarity, and low solubility, which may restrict their clinical applicability. The results emphasize the importance of balancing inhibitory potency with favourable physicochemical and pharmacokinetic properties during the development of clinically effective urokinase inhibitors. This review highlights the current challenges associated with developing uPA inhibitors into clinically useful drugs. A better understanding of the structure and mechanism of action of uPA inhibitors will provide a valuable foundation for the rational design of a new generation of compounds effective against uPA, intended for use in the treatment of cancer and other diseases.

PMID 42636784
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