Drug Database
PL

plasminogen activator (tisokinase / tisokinase, Kowa / Hapase)

✓ Approved

Asahi Kasei · therapeutic agent

What is plasminogen activator?

plasminogen activator is a therapeutic agent developed by Asahi Kasei. It is approved for therapeutic indications via injectable (others) or intravenous (iv).

Drug Profile

Brand Namestisokinase, tisokinase, Kowa, Hapase
CompanyAsahi Kasei
RouteInjectable (Others), Intravenous (IV)
StatusApproved
Sources: ClinicalTrials.gov, Asahi Kasei

Therapeutic Indications

plasminogen activator is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Cardiac disordersMyocardial infarction✓ Approved

Related Research Articles

PubMedWorld journal of otorhinolaryngology - head and neck surgery2026-07-25

Decreased Production of Tissue Plasminogen Activator in Endothelial Cells From Nasal Polyps.

Zhang Qian-Qian QQ, Zhang Chen C, Chen Jia-Ni JN, Cheng Fu-Ying FY et al.

Previous studies have demonstrated that chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by excessive fibrin deposition which is related to impaired production of tissue plasminogen activator(t-PA) by epithelial cells. This study aims to evaluate whether t-PA expression in endothelial cells is also decreased under the inflammatory milieu of CRSwNP. Vascularity and proangiogenic genes expression in polyp tissues from eosinophilic CRSwNP (eCRSwNP) and non-eosinophilic CRSwNP (neCRSwNP) were assessed by immunohistochemistry and real-time PCR. Single-cell RNA sequencing data set of CRS, Immunohistochemistry were used. Human primary nasal endothelial cells were stimulated by IL-13 and IFN-γ with or without retinoic acid. We observed the increased expression of proangiogenic genes and vascularity in both eCRSwNP and neCRSwNP. Single-cell RNA sequencing and immunostaining revealed that t-PA expression was decreased in endothelial cells of polyp tissues. In vitro study, IL-13 and IFN-γ could significantly attenuate t-PA expression in endothelial cells, which can be rescued by retinoic acid. Our findings showed a significant contribution of endothelial cells in the production of t-PA in sinonasal tissues. Furthermore, the levels of t-PA in endothelial cells could also be impaired in the inflammatory environment of CRSwNP. Retinoic acid could restore t-PA expression in endothelial cells impaired by inflammatory cytokines (including IL-13 and IFN- γ), thus degrading the deposited fibrin in polyp tissue.

PMID 42500055
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PubMedBlood advances2026-07-25

Tenecteplase (TNK) and other TNK formulations lose PAI-1 resistance in their two-chain form: Comparison with alteplase.

Liu Zikou Z, Tippett Isabel I, McCutcheon Fiona M FM, Keragala Charithani B CB et al.

Alteplase is synthesized as a single-chain protease that requires plasmin-mediated conversion to its fully active two-chain form for maximal thrombolysis. Tenecteplase (TNK), an alteplase variant, is widely regarded as being more fibrin-selective and more resistant to plasminogen activator inhibitor-1 (PAI-1) than alteplase. However, the PAI-1 sensitivity of TNK after two-chain conversion, and that of newly available TNK formulations, has not been evaluated. Alteplase and four TNK formulations: Metalyse (Boehringer Ingelheim), Tenectase (Gennova, India), GenetPA (BioApower, China) and Mingfule (CSPC, China) were compared in their native state and after two-chain conversion. Proteolytic activity, PAI-1 resistance and binding were evaluated using amidolytic assay, fibrinolysis assays and Western blotting. Alteplase, but not Metalyse was converted into its two-chain form in plasma in a fibrinogen-dependent manner, resulting in off-target fibrinogenolysis. When directly reconstituted from the manufacturers vial (native form), TNK was ~4-fold more resistant to PAI-1 than alteplase; however, two-chain conversion significantly reduced PAI-1 resistance by ~40%, concomitant with increased PAI-1 binding. Native Metalyse contained ~3-fold more pre-existing two-chain species than the other TNK formulations, explaining its higher amidolytic activity. However, after two-chain conversion, all TNK formulations showed similar fibrinolytic activity albeit with substantially reduced PAI-1 resistance. Metalyse and all new TNK formulations display similar fibrinolytic activity in their fully active two-chain states, but this is associated with substantial loss of PAI-1 resistance, challenging the view that the fully active two-chain form of TNK maintains PAI-1 resistance during thrombolysis.

PMID 42498282
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PubMedRevista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia2026-07-25

Hemostatic safety profile of estetrol vs. ethinylestradiol in oral contraceptives: a systematic review and meta-analysis.

Lemos Maria Julia MJ, Ferraz Jacqueline Maia JM, Queiroz Laura Fonseca LF, Diniz Alice França AF et al.

To evaluate the hemostatic profile of estetrol/drospirenone (E4/DRSP) compared with ethinylestradiol/drospirenone (EE/DRSP) in adult women. A systematic review and meta-analysis of randomized controlled trials (RCTs) was performed according to PRISMA guidelines. Eligible studies compared E4/DRSP with EE/DRSP in adult women and assessed coagulation, anticoagulation, or fibrinolytic markers. Three RCTs (n=183) met inclusion criteria. Data were extracted independently, and pooled mean differences (MD) were calculated using random-effects models. Compared to EE/DRSP, E4/DRSP was associated with higher protein S activity (MD = 21.23; 95% CI: 11.83 to 30.64; p<0.00001) and lower levels of fibrinogen (MD = -24.17; 95% CI: -39.15 to -9.19; p=0.002), plasminogen (MD = -27.28; 95% CI: -27.28 to - 22.89; p<0.00001), and SHBG (MD = -183.38; 95% CI: -183.38; 95% CI: -210.93 to -155.84; p<0.00001). No significant differences were observed for D-dimer and antithrombin. Protein C activity was higher in the EE group, though this was an isolated finding with limited interpretability. E4/DRSP demonstrates a more favorable hemostatic profile than EE/DRSP, potentially reducing thrombotic risk. Despite the limited number of RCTs, consistency across markers supports E4 as a safer estrogenic component for contraceptive formulations, with implications for women at increased risk of venous thromboembolism.PROSPERO registry: #CRD420251074961.

PMID 42500171
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PubMedJournal of environmental sciences (China)2026-07-25

An oxidation process of tetracycline with low products toxicity by Fe single-atom peroxydisulfate activator from microalgae.

Chen Qinqin Q, Cheng Peiyuan P, Zhou Daixi D, Ding Lei L et al.

Recently, advanced oxidation processes based on single-atom catalysts have been extensively adopted in water treatments. Although some studies have identified low toxicity in degradation products, the mechanistic understanding remains unclear. In this work, an efficient catalyst named BC-Fe was developed by anchoring atomically dispersed Fe onto biochar (BC) derived from microalgae using a convenient impregnation method. The catalyst of BC-Fe enhanced performance in activating peroxydisulfate (PDS) for the degradation of tetracycline (TC). The BC-Fe/PDS system demonstrated faster TC degradation rate constant of 0.073 min-1. Mechanism investigations revealed that the atomically dispersed Fe-N4 sites activate PDS via efficient electron transfer, generating high-valent metal-oxo (HVMO) species as the primary reactive oxidants. These HVMO species selectively oxidized electron-rich moieties in TC, leading to progressive ring-opening and mineralization into low-toxicity intermediates. Moreover, TC served as an electron donor to the HVMO species, enabling their reduction and forming a favorable cycle of valence states of Fe. This work provides an efficient and environment-benign strategy for the oxidation of antibiotics with minimal secondary pollution.

PMID 42498355
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PubMedFrontiers in aging neuroscience2026-07-25

JAK/STAT signaling pathway inhibitors in neurodegenerative diseases: current status and future perspectives.

Yang Hai-Xia HX, Su Bo-Wei BW, Bao Ya-Nan YN, Wang Wen-Hao WH et al.

Neurodegenerative diseases (NDDs) are a major public health concern characterized by the progressive loss of neurons, ultimately leading to neuronal death and causing a sustained decline in brain function or physical motor abilities. Major examples include Alzheimer's disease (AD) and Parkinson's disease (PD). Currently, NDDs lack effective curative methods, and their pathological process primarily involves misfolded protein aggregation, oxidative stress, and neuroinflammation. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway, as a central hub for cytokine signaling, has recently been found to play a key role in neuroinflammation and immune regulation in NDDs. This review systematically elucidates the core mechanisms of the JAK/STAT pathway in NDDs, including the regulation of microglial and astrocytic reactivity, the impact on blood-brain barrier integrity, and involvement in energy metabolism abnormalities. On this basis, we have reviewed and evaluated various therapeutic strategies targeting this pathway, focusing on small-molecule JAK inhibitors such as baricitinib and tofacitinib, and have analyzed their mechanisms of action, preclinical efficacy, and potential side effects. In addition, this article provides a forward-looking perspective on the future research directions of the JAK/STAT pathway from the perspective of anti-neuroinflammation to promote neuroregeneration therapy, aiming to offer theoretical references and new ideas for the clinical translational research of this pathway.

PMID 42499556
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PubMedFrontiers in immunology2026-07-25

Macrophage reprogramming through scavenger receptor-guided and cathepsin B-triggered nanodelivery: from intracellular mechanisms to translational applications.

Huang Yang Y, Cai Le L, Yan Xu X, Tong Kaiyi K et al.

Macrophages are highly plastic innate immune cells. Their functional states are dynamically shaped by inflammatory signals, metabolic stress, and disease-associated remodeling. In cancer and atherosclerosis, pathological macrophages contribute to immune suppression, plaque destabilization, and therapeutic resistance, making their reprogramming a critical translational goal. Recent advances in nanomedicine provide new opportunities to manipulate macrophage behavior by combining selective cellular entry with conditionally controlled intracellular release. This review focuses on scavenger receptor-guided and cathepsin B-triggered nanodelivery systems as a mechanism-aligned strategy for phenotypic remodeling. While scavenger receptors provide selective molecular gateways enriched in diseased macrophage populations, cathepsin B serves as an endogenous trigger for subsequent nanocarrier disassembly and payload release. We discuss how aligning targeted internalization and enzymatic release can reshape macrophage function. We also examine how these platforms engage intracellular vulnerability networks, highlighting signal transducer and activator of transcription 3 (STAT3) as a translationally relevant node that stabilizes pathological states rather than an exclusive mechanistic axis. Finally, we assess major translational challenges, including off-target sequestration, target heterogeneity, and functional bioavailability. This review aims to advance the translational development of macrophage-centered immunomodulatory therapies by linking nanodelivery design to macrophage biology and disease-relevant intracellular mechanisms.

PMID 42500677
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