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urokinase (Breokinase / Alphakinase / Thrombolase)

✓ Approved

Mitsubishi Tanabe Pharma Corporation · PLAU

什么是 urokinase？

urokinase 是一种治疗药物，由Mitsubishi Tanabe Pharma Corporation研发。该药已获批，用于治疗相关适应症。

药物档案

商品名Breokinase, Alphakinase, Thrombolase
公司Mitsubishi Tanabe Pharma Corporation
分子靶点PLAU
状态Approved
来源： ClinicalTrials.gov, Mitsubishi Tanabe Pharma Corporation

作用机制

分子靶点

urokinase 作用于 1 个分子靶点：

PLAUplasminogen activator, urokinase (URK, UPA)
需要更深入的分析？Noah AI 可解释复杂机制并与同类药物比较。

治疗适应症

urokinase 针对 1 个适应症，涉及 1 个治疗领域。

治疗领域疾病/病症分期
Respiratory, thoracic and mediastinal disordersPulmonary thrombosis✓ Approved

相关研究文献

PubMedJournal of the American Heart Association2026-10-25

Outcomes of Intra-Arterial Urokinase After Endovascular Reperfusion for Acute Ischemic Stroke Due to Cardioembolism: A Secondary Analysis of the POST-UK Trial.

Song Jiaxing J, Zhao Xuexiao X, Li Gaoming G, Zhou Mingrui M et al.

Whether adjunctive intra-arterial thrombolysis improves outcomes in patients with acute ischemic stroke due to cardioembolism remains unclear. This study aimed to investigate the efficacy and safety of adjunctive intra-arterial urokinase in patients with acute ischemic stroke due to cardioembolism who achieved near-complete to complete reperfusion. This study was a secondary analysis of the POST-UK (Adjunctive Intra-Arterial Urokinase After Near-Complete to Complete Reperfusion for Acute Ischemic Stroke) trial, which was conducted from November 15, 2022, to March 29, 2024. Patients were randomly assigned to the intra-arterial urokinase group or the control group. The primary outcome was disability-free survival at 90 days, defined as a modified Rankin Scale score of 0 to 1. Safety outcomes included 90-day all-cause death, symptomatic intracranial hemorrhage and any intracranial hemorrhage within 48 hours. Among 209 patients with cardioembolism (median age 73 [interquartile range, 63-81] years; 45.9% men), 106 were assigned to the control group and 103 to the intra-arterial urokinase group. Compared with the control group, adjunctive intra-arterial urokinase significantly increased the odds of disability-free survival at 90 days (adjusted risk ratio, 1.49 [95% CI, 1.08-2.06]; P=0.01; inverse probability of treatment weighting adjusted risk ratio, 1.47 [95% CI, 1.04-2.09]; P=0.03). No significant differences were found between groups in 90-day mortality rate, symptomatic intracranial hemorrhage, or any intracranial hemorrhage within 48 hours. In patients with acute ischemic stroke due to cardioembolism who achieved near-complete to complete reperfusion, adjunctive intra-arterial urokinase significantly improved disability-free survival at 90 days without increasing the risk of death or intracranial hemorrhage. URL: ChiCTR.org.cn; Unique identifier: ChiCTR2200065617.

PMID 42924849
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PubMedFASEB journal : official publication of the Federation of American Societies for Experimental Biology2026-10-25

SERPINE2 At the Granulosa Cell-Matrix Interface: Emerging Mechanisms in Follicular Development and Ovarian Function.

Chen Xiaowei X, Chu Mingxing M

Serpin family E member 2 (SERPINE2), also known as protease nexin-1, is a secreted serpin enriched in ovarian granulosa and cumulus-cell compartments. Its location is biologically important because follicle growth, selection, atresia and ovulation all require spatially controlled extracellular proteolysis. Recent experiments have begun to define how SERPINE2 is regulated and what it may do in the ovary. In human granulosa-lutein cells, bone morphogenetic protein 2 (BMP2) induces SERPINE2 through ALK3-dependent SMAD2/3-SMAD4 and p38 MAPK signaling and is accompanied by reduced production of urokinase- and tissue-type plasminogen activators. In buffalo granulosa cells, FOXL2 activates SERPINE2 transcription, whereas promoter-associated H3K9me3 is linked to its repression in atretic follicles; SERPINE2 perturbation affects proliferation, apoptosis and steroid output. In FecB-genotyped sheep granulosa cells, SERPINE2 alters TERT expression, relative telomere length, proliferation, ovulation-related genes and estradiol secretion. Together, these studies support a model in which intracellular differentiation and chromatin programmes converge on a secreted inhibitor that adjusts the extracellular proteolytic environment and thereby modifies granulosa-cell state. However, the causal chain from individual protease targets to matrix remodeling, receptor signaling and whole-animal fertility remains incomplete. WNT/beta-catenin and ERK1/2 are plausible downstream candidates, but their dependence on SERPINE2 has not been demonstrated in ovarian cells. This review integrates the direct ovarian evidence with follicular matrix biology, separates established mechanisms from tissue-extrapolated hypotheses, and defines experiments needed to determine whether SERPINE2 is principally a marker of follicular state, a local proteolytic buffer or a tractable regulator of ovarian function.

PMID 42921654
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PubMedFrontiers in pediatrics2026-10-25

Case Report: Multidisciplinary and individualized management of periprocedural arterial thrombosis and ischemic stroke in children: a three-case series.

Zhou Guoxiang G, Ge Wen W, Wan Hao H, Chen Rui R et al.

Pediatric arterial thromboembolism is rare but may cause limb loss, extensive cerebral infarction, permanent disability, or death. Evidence guiding reperfusion therapy in children remains limited. We describe three periprocedural events treated according to their vascular territory, threatened tissue, and bleeding risk. A male neonate born at 37 weeks' gestation developed catheter-associated left external iliac-femoral arterial thrombosis after umbilical arterial catheterization during treatment for shock and respiratory illness. Intravenous urokinase and low-molecular-weight heparin achieved complete thrombus resolution on ultrasonography six days after diagnosis. A 5-year-and-5-month-old boy developed acute left internal carotid-middle cerebral artery occlusion with extensive left hemispheric infarction three days after thoracoscopic resection of pulmonary sequestration. Emergency stent-retriever thrombectomy with aspiration achieved immediate recanalization, which persisted at one week; independent ambulation was restored after rehabilitation, although mild right upper-limb symptoms remained at discharge. A 4-month-old boy developed right frontotemporal-insular ischemic infarction after balloon angioplasty for recurrent aortic coarctation. Because no retrievable intracranial large-vessel occlusion was identified and the recent cardiac intervention increased the bleeding risk, aspirin, low-molecular-weight heparin, and supportive treatment were administered. Follow-up MRI one week after diagnosis showed regression of the initial lesion but revealed a new right thalamic lesion suspicious for acute infarction. These heterogeneous cases highlight the need for prompt vascular imaging and individualized multidisciplinary management based on the vascular territory, threatened tissue, patient size, recent procedures, bleeding risk, and procedural feasibility. As a descriptive case series, this report does not establish the comparative efficacy of the treatment strategies.

PMID 42922988
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PubMedCurrent medical research and opinion2026-10-23

Cost-effectiveness of cladribine tablets for the treatment of active relapsing-remitting multiple sclerosis in the United Kingdom.

Jones Michelle M, Alexopoulos Stamatia T ST, Fontrier Anna-Maria AM, Harty Gerard G et al.

The approved indication of cladribine tablets has recently been expanded in the United Kingdom for the treatment of all adult patients with active relapsing multiple sclerosis. This analysis assessed the cost-effectiveness of cladribine tablets from the perspective of the National Health Service in patients with active relapsing-remitting multiple sclerosis (RRMS). A cohort-based Markov model with 11 health states (10 disability states plus death) was developed. In addition to best supportive care without disease-modifying therapy (DMT), 12 recommended DMTs were included as comparators to cladribine tablets over a 50-year horizon. Treatment effects were modelled using hazard ratios for 6-month confirmed disability progression (CDP); relapses and drug-related adverse events were modelled via annualized relapse rates and event probabilities. Associated costs (inflated to 2023 pounds sterling) and quality-adjusted life year (QALY) losses were discounted at 3.5% annually. Sensitivity analyses were conducted. Cladribine tablets were dominant (i.e. less costly and more effective) vs ponesimod, ocrelizumab, ofatumumab, dimethyl fumarate, diroximel fumarate, and teriflunomide in pairwise comparisons. Over a lifetime horizon, the model predicted discounted cost-savings with cladribine tablets vs high-efficacy comparators (ponesimod, ocrelizumab, and ofatumumab). In most scenarios, the cost-savings resulted from lower lifetime drug acquisition costs due to the unique fixed course posology of cladribine tablets, in addition to delayed disease progression. Sensitivity analyses supported the base case that cladribine tablets are cost-effective vs ponesimod, ofatumumab, and ocrelizumab; the main source of uncertainty was related to the large credible intervals associated with 6-month CDP. This economic analysis demonstrated that cladribine tablets are a cost-effective treatment option for patients with active RRMS.

PMID 42908358
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PubMedThe Journal of biological chemistry2026-10-23

Glycan-mediated binding to collagen by a C-type lectin-like domain of the endocytic receptor Endo180 / uPARAP.

Drickamer Kurt K, Jégouzo Sabine A F SAF, Feinberg Hadar H, Lasanajak Yi Y et al.

The primary role of the multidomain endocytic receptor designated Endo180 or uPARAP (urokinase-plasminogen activator receptor associated protein) is to facilitate internalization of collagen for lysosomal degradation during matrix remodeling in tissues. However, Endo180 interacts both with collagen and sugars and the relationship between these activities is not fully defined. While collagen-binding activity is associated with a fibronectin type 2 domain and an adjacent C-type lectin-like domain 1 (CTLD1), sugar-binding activity resides in CTLD2. Potential interactions of CTLD2 with various glycans have been examined by glycan array screening, solid phase binding assays, x-ray crystallography, and molecular modeling. Glycan array screening suggests potential interactions with exposed GlcNAc residues on truncated core 2 and core 4 O-linked glycans, but such structures are rare. Binding competition assays demonstrate that the disaccharide Glcα1-2Gal, found attached to hydroxylysine residues in collagens, is an alternative ligand. X-ray crystallography analysis of a complex of α-methyl fucoside with CTLD2 provides a basis for modeling how the Glcα1-2Gal disaccharide attached to hydroxylysine can be accommodated in the binding site with both sugar residues making favorable interactions with the protein. In direct binding studies, types IV and V collagen, but not type I collagen, bind to CTLD2 through the sugar-binding site. These results provide direct evidence that sugar-binding activity of CTLD2 contributes to binding of heavily glycosylated collagens. Although other endogenous mammalian glycan targets for CTLD2 are rare, CTLD2 can additionally interact with pathogen glycans such as poly-N-acetylglucosamine, contributing to the general role of Endo180 as a scavenger receptor.

PMID 42914018
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PubMedJournal of nuclear medicine : official publication, Society of Nuclear Medicine2026-10-23

Prognostic Value of 68Ga-NOTA-AE105 uPAR PET/CT in Resected Non-Small Cell Lung Cancer: A Single-Center Prospective Study.

Soldath Patrick P, Clausen Malene M MM, Loft Annika A, Colville-Ebeling Bonnie B et al.

Non-small cell lung cancer shows wide variability in outcomes after curative-intent resection. 18F-FDG PET/CT is indispensable for staging but primarily reflects glucose metabolism rather than the invasion-related tumor biology that may contribute to recurrence. 68Ga-NOTA-AE105 PET/CT images the urokinase-type plasminogen activator receptor (uPAR), a cell-surface mediator of local invasion and metastatic spread. We assessed whether preoperative 68Ga-uPAR PET/CT is prognostic for postoperative recurrence. Methods: We conducted a single-center cohort study of patients with resectable lung adenocarcinoma or squamous cell carcinoma who were prospectively enrolled to undergo preoperative 68Ga-uPAR PET/CT in addition to standard-of-care 18F-FDG PET/CT. Primary tumor SUVmean and SUVmax were measured for both tracers, and tumor tissue uPAR expression was quantified by immunohistochemistry (H-score). Postoperative recurrence was the primary endpoint and was analyzed in a competing-risks framework with death as a competing event. The primary prognostic analyses evaluated 68Ga-uPAR SUVs, 18F-FDG SUVs, and uPAR H-score as continuous variables using univariable cause-specific Cox models. A 1.5-y horizon was used for exploratory Youden-derived high versus low groups, for which cumulative incidence of recurrence was estimated using the Aalen-Johansen method. Trial registration number is NCT02755675 Results: Thirty-seven patients comprised the analysis cohort, of whom 14 developed recurrence during a median follow-up of 2.38 y (interquartile range, 1.97-8.20 y). Four patients died without prior recurrence. 68Ga-uPAR uptake correlated with tumor tissue uPAR expression, whereas 18F-FDG uptake did not. As continuous prognostic factors, higher 68Ga-uPAR SUVmax (hazard ratio, 2.16; 95% CI, 1.34-3.49; P = 0.002) and higher uPAR H-score (hazard ratio, 1.04 per unit; 95% CI, 1.01-1.08; P = 0.017) were associated with recurrence; 68Ga-uPAR SUVmean showed borderline evidence of association (P = 0.053), whereas 18F-FDG uptake was not prognostic. Exploratory 1.5-y threshold analyses showed greater early recurrence in the high SUVmean and high H-score groups; the SUVmax comparison did not reach statistical significance. Conclusion: Preoperative 68Ga-uPAR PET uptake reflected tumor uPAR expression and was associated with early postoperative recurrence, whereas 18F-FDG uptake was not prognostic in this cohort. These findings suggest that uPAR PET captures invasion-related tumor biology that is not fully reflected by glucose metabolism imaging. External validation is required.

PMID 42914185
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