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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

PubMedJournal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia2026-10-14

Implementation of IRRAflow active irrigation in neurosurgical patients: A case series and literature overview.

Palermoit Matteo M, Policicchio Domenico D, La Torre Domenico D, Romozzi Marina M et al.

Active fluid management systems such as IRRAflow aim to overcome the limitations of passive external drains by enabling simultaneous automated irrigation and aspiration in a closed circuit. In acute and chronic subdural hematoma (a/cSDH), it enables active subdural irrigation, whereas in subarachnoid hemorrhage (SAH), intraventricular hemorrhage (IVH), and ventriculitis, it allows continuous ventricular CSF exchange and, when indicated, intrathecal administration of therapeutic agents. A literature analysis identified studies reporting IRRAflow use for SAH, SDH, IVH, or ventriculitis. Additionally, a single-center retrospective series of 13 consecutive patients treated with IRRAflow was analyzed, focusing on clinical course, complications, and outcomes. Thirty studies comprising 345 patients were included in the literature analysis. In cSDH, clinical resolution was reported in 40 cases (90.9%), with recurrence in 3 patients (6.8%) and no reported infections or catheter obstructions. In aSDH, only 1/11 patient experienced clinical deterioration and required conversion to craniotomy. In IVH, outcomes were more variable, with complete resolution in 14/36 cases (38.9%), clinical improvement in 15/36 (41.7%), deterioration in 1/36 (2.8%), and death in 6 (16.7%). In ventriculitis, largely reported in case reports and small case series, resolution or improvement was achieved in 27/35 patients (77.1%), while mortality was 8/35 (22.9%). In aSAH, 7/23 (30.4%) patients died from complications of the hemorrhage. Vasospasm occurred in 7/23 (30.4%) patients, including two who subsequently died, while 2/23 (8.7%) required permanent shunting; both were survivors who had experienced vasospasm. No device-related complications were reported. Our institutional cohort included 6 patients with IVH, 4 with cSDH, and 3 with ventriculitis. Among the IVH cases, 3/6 patients died before discharge, 1 died during follow-up, whereas the other 2 had an mRS score of 3 and 2 at last follow-up. Among patients with cSDH, 3/4 achieved favorable functional recovery at follow-up, while 1/4 died before discharge because of complications unrelated to IRRAflow. Among the 3 patients with ventriculitis, 1 died following a complication related to urokinase infusion after adjunctive urokinase administration, whereas the remaining 2 (66.7%) achieved resolution or improvement. Both the institutional cohort and the literature search showed promising results for the use of IRRAflow in cSDH. Results on ventriculitis, aSAH and aSDH are still uncertain due to the small sample sizes. Regarding IVH, neither the exploratory review nor our institutional case series identified a clear clinical benefit associated with IRRAflow use. Nevertheless, the available evidence remains limited by predominantly observational, small and heterogeneous studies, precluding comparative conclusions.

PMID 42874423
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PubMedChemical science2026-10-14

Beyond the catalytic serine: selective protease engagement with covalent macrocyclic activity-based probes.

Barrueco Marina M, Hyde Ellie E, Sawtell Ella E, Mills Jack V JV et al.

Activity-based probes (ABPs) are widely used to profile serine protease activity - enzymes central to diverse physiological and pathological processes - but most rely on covalent modification of the conserved catalytic serine residue, often resulting in poor selectivity across related proteases. Here, we introduce covalent macrocyclic activity-based probes (cmABPs) that selectively target non-catalytic residues within serine protease active sites. By combining phage display with systematic electrophile scanning, we identify macrocyclic scaffolds that position sulfur(vi) fluoride (SuFEx) electrophiles to covalently engage alternative nucleophiles such as lysine and tyrosine. Applied to plasma kallikrein, this approach yielded a macrocyclic scaffold that was converted into covalent probes via fluorosulfate scanning. Remarkably, small changes in electrophile structure produced large, tuneable differences in covalent kinetics, with benzenesulfonyl fluoride derivative 23 achieving rapid and complete protein modification. Biochemical and mass spectrometry analyses confirmed selective modification of an active-site lysine by 23, along with robust performance in complex biological samples. Extension to urokinase plasminogen activator further demonstrates the generality of this strategy. More broadly, this work establishes electrophile scanning within macrocyclic scaffolds as a general approach for tuning covalent reactivity and provides a blueprint for designing selective probes that move beyond catalytic-residue targeting.

PMID 42871609
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PubMedClinical and translational medicine2026-10-12

A single-cell census of pulmonary endarterectomies tissue across different anatomical regions in chronic thromboembolic pulmonary hypertension.

Zhang Rui R, Zhang Yunlong Y, Li Huiting H, Zhang Jing J et al.

Pulmonary endarterectomy (PEA) remains one of potentially curative options for chronic thromboembolic pulmonary hypertension (CTEPH). The operation can remove proximal thromboembolic materials and their secondary branches. However, the cellular landscape and pathological features across different anatomical regions remain limited understood. Ten patients with CTEPH undergoing PEA surgery and six reference distal pulmonary arteries were conducted single-cell transcriptomics to profile the cellular composition of the main and its bifurcate portion. Pronounced muscularised and fibrotic thrombi organisation were presented in the main portion, and the proportion of mononuclear phagocytes was significantly increased. Inflammatory response and pro-inflammatory activity were attributed to CD8+ effector T cells and nature killer cells subsets and a M1-like (high IL1B and TNF, minimal IL6) phenotypic macrophage subcluster. The colander-like lesions were dominant in the bifurcate portion, and the percentage of plasma cells was markedly increased. Immune dysregulation was induced from CD4 naïve T cells, and a downregulation of M2-like macrophage infiltration into the vascular wall. The expression of plasminogen activator, urokinase receptor, urokinase receptor (PLAUR; plasminogen activator) were observed in M2-like (high MRC1 and CD163, virtually no IL1B or TNF) macrophage in bifurcate portion. Notably, one of smooth muscle cells (SMCs) subclusters in the bifurcate portion gained more significantly myofibroblast markers than those in the main portion, and other subclusters remained the function of SMCs. The regions with colander-like lesions changes had more obviously T cell and macrophages driving immune-inflammatory response and SMCs differentiation, suggesting that combining therapeutic interventions after surgical removal of accessible thrombus may be beneficial. This study reveals the comprehensive cellular composition in main/lobar and bifurcate pulmonary endarterectomy (PEA) specimens at the single-cell level. The bifurcate regions with colander had more obviously T cell and macrophages driving immune-inflammatory response and smooth muscle cells (SMCs) differentiation, however, the remodelling of distal or micro-vessels still remained.

PMID 42860722
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PubMedNeurosurgery2026-10-12

Ventriculolumbar Irrigation Effects on Delayed Cerebral Infarction and Outcome After Aneurysmal Subarachnoid Hemorrhage: A Prospective Registry Study.

Overstijns Manou M, Scheiwe Christian C, El Rahal Amir A, Fistouris Panagiotis P et al.

Aneurysmal subarachnoid hemorrhage (aSAH) remains associated with high morbidity and mortality, largely determined by delayed cerebral ischemia (DCI). Active blood clearance and vasodilation (ABCD) therapy targets key pathophysiological mechanisms of DCI by enhancing the clearance of blood from cerebrospinal fluid and counteracts vasospasm through continuous intrathecal fibrinolytic and spasmolytic irrigation. Although ABCD therapy has previously been implemented using technically demanding treatment approaches, this study introduces ventriculolumbar irrigation (VLI) as a simplified, bedside-applicable method. This study evaluates whether VLI-based ABCD therapy is associated with an improvement in DCI and morbidity. In this prospective registry study, consecutive aSAH patients treated with the novel VLI-based ABCD therapy (pressure-controlled VLI with urokinase and on-demand nimodipine) between 2019 and 2025 were compared with matched controls receiving standard care. The primary outcome was the incidence of DCI and the secondary outcome was modified Rankin Scale (mRS) at 180 days. Seventy-two patients treated with VLI-based ABCD therapy were compared with 144 matched controls. VLI treatment was associated with significantly lower rates of DCI (9.7% vs 29.9%, P < .001), morbidity (mean mRS 2.33 vs 3.37, P < .001), and shunt-dependent hydrocephalus (9.7% vs 31.9%, P < .001). Compared with isolated, passive cerebrospinal fluid drainage, VLI was associated with lower DCI rates (9.7% vs 30.7%, P < .001) and reduced morbidity (mean mRS 2.33 vs 3.39, P < .001). The novel and simplified VLI therapy was associated with considerably improved outcomes: lower DCI rates and shunt-dependent hydrocephalus. VLI offers a bedside technique to actively remove intrathecal blood and deliver intrathecal spasmolysis for the prevention of DCI. Randomized trials are needed to confirm these findings.

PMID 42861997
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PubMedCancer communications (London, England)2026-10-11

Targeting TREM2+ and TIMD4+ Macrophages Reprograms the Tumor Microenvironment and Enhances PD-1 Blockade Efficacy in Intrahepatic Cholangiocarcinoma.

Li Yao Y, Liu Hongwen H, Xu Lei L, Huang Lili L et al.

Background: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer. Macrophages are crucial components of the tumor microenvironment (TME). Triggering receptor expressed on myeloid cells 2-positive (TREM2+) macrophages have recently emerged as potent pro-tumor progress players in several cancers. However, the heterogeneity and tumor-promoting mechanisms of macrophages especially TREM2+ macrophages in ICC remain systematically unexplored. Therefore, this study aimed to systematically elucidate the heterogeneity of macrophages in ICC, with a specific focus on the pro-tumor role of TREM2+ macrophages. Methods: We collected tumor tissues, adjacent nontumor tissues, and tumor-adjacent border tissues from 16 ICC patients. These samples were subjected to single-cell RNA sequencing and spatial transcriptomic sequencing, followed by comprehensive analysis. The findings were further validated through flow cytometry, immunohistochemistry, multiplex immunofluorescence, and in vitro cellular assays. Furthermore, we established an ICC model using genetically engineered (Trem2-/- ) mice as a validation cohort to corroborate the discoveries from human samples. Results: Macrophages are important prognostic factors in ICC, with functional heterogeneity. TREM2+ macrophages in tumor tissues promote immune suppression by exhausting CD8+ T cells and inducing the generation of regulatory T cells to produce. At the tumor border region, TREM2+ macrophages enhance ICC invasion via the urokinase-type plasminogen activator-urokinase-type plasminogen activator receptor axis and induce hepatic stellate cell conversion to myofibroblastic cancer-associated fibroblast, forming a physical immune barrier that impedes CD8+ T cell infiltration in tumor tissues. TIMD4+ macrophages in adjacent tissues also suppress CD8+ T cell function. Combining anti-Trem2 and anti-Timd4 with anti-Pd-1 antibodies significantly improved treatment outcomes in the ICC mice. Conclusions: TREM2+ and TIMD4+ macrophages are key regulators of the immunosuppressive TME in ICC. Targeting Trem2 and Timd4 enhances the effectiveness of anti-Pd-1 therapy in ICC mouse models.

PMID 42856794
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PubMedBJU international2026-10-11

Prognostic biomarkers in non-muscle-invasive bladder cancer: biological basis and evidence.

Wang Jinghong J, Zhao Yitao Y, Ye Yushan Y, Qi Xiaolong X et al.

To review prognostic and treatment-response biomarkers for non-muscle-invasive bladder cancer (NMIBC), with particular attention to biological function, specimen type, assay method, statistical evidence, and possible clinical use. We conducted a focused narrative search of PubMed, Web of Science, and the Cochrane Library for English-language human studies published from January 2015 to August 2026, supplemented by earlier pivotal studies and reference-list screening. Priority was given to NMIBC cohorts reporting recurrence, progression, survival, or response to intravesical therapy. We considered cohort specificity, sample size, multivariable analysis, testing in an independent population, and assay standardisation. Tumour-tissue markers such as stromal antigen 2 (STAG2), fibroblast growth factor receptor 3 (FGFR3), fibroblast activation protein-α, the urokinase plasminogen activator system, and cadherins are linked to chromosomal stability, growth-factor signalling, stromal remodelling, extracellular-matrix invasion, and epithelial-mesenchymal transition. Urinary RNAs and plasma circulating tumour DNA permit non-invasive sampling, although results depend on specimen handling and assay conditions. Blood-derived inflammatory indices are inexpensive but non-specific. Most evidence comes from retrospective single-cohort studies; reported effects and cut-offs are not always consistent, and few markers materially improve clinicopathological models. None of the biomarkers reviewed can currently replace guideline-based risk stratification or cystoscopic surveillance. Future studies should define assays and thresholds prospectively, test them in independent cohorts, and show that adding a biomarker improves prediction and patient management at an acceptable cost.

PMID 42860325
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