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

PubMedFrontiers in immunology2026-10-15

Hemin suppresses interferon responses in periodontal cell models through JAK2-STAT1 inhibition.

Huang Xiaoyu X, Gruber Reinhard R, Panahipour Layla L

Hemin, an oxidized heme species released during erythrocyte breakdown, is detectable in gingival crevicular fluid during periodontal inflammation, but its effects on local immune signaling remain unclear. We investigated whether hemin modifies cytokine-induced interferon responses in HSC-2 oral squamous cell carcinoma cells and primary human gingival fibroblasts. Cells were stimulated with interleukin-1β and tumor necrosis factor-α, or with interferon-γ, in the presence or absence of hemin. Transcriptomic changes were assessed by RNA sequencing and pathway analysis, and selected transcripts and proteins were validated by reverse-transcription quantitative PCR, enzyme-linked immunosorbent assay, immunoblotting, and immunofluorescence. Ligand-kinase interactions were examined by molecular docking and molecular dynamics simulations, and recombinant Janus kinase 2 activity was measured in a cell-free assay. Hemin preferentially suppressed an interferon-associated gene network, including CXCL10, CXCL11, MX1, OAS1, IFIT1, IFIT3, and ISG15, while nuclear factor κB-associated responses were comparatively preserved. Hemin also reduced signal transducer and activator of transcription 1 Tyr701 phosphorylation and nuclear accumulation induced by either the cytokine combination or interferon-γ. Computational analyses predicted stable hemin interactions within conserved ATP-binding pockets of Janus kinases, and the cell-free assay demonstrated inhibition of recombinant Janus kinase 2. Together, these findings show that hemin attenuates interferon-associated transcription in periodontal cell models, consistent with inhibition of the Janus kinase 2-signal transducer and activator of transcription 1 axis. This mechanism may enable blood-derived hemin to modify local mucosal immune signaling, although its relevance to periodontal tissues and antiviral defense requires confirmation in organotypic, infection, and in vivo models.

PMID 42876722
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PubMedACS sensors2026-10-15

Cleavage Activity Adjustment of the CRISPR/Cas System for Enhanced Diagnostics.

Zhao Yining Y, Qiao Panpan P, Yang Min M, Chen Ling L et al.

The CRISPR/Cas system, known for its high precision and efficiency in genome editing, has garnered significant interest and demonstrated potential in diagnostics, owing to advantages such as sensitivity and cost-effectiveness. However, the application of the CRISPR/Cas system in diagnostics is constrained by two inherent challenges. On one hand, the sensitivity of the CRISPR/Cas system for the direct detection of low-abundance targets remains to be further improved for the demands of practical detection. On the other hand, the integration of nucleic acid amplification with the CRISPR/Cas system in one-pot assays presents difficulty of balance between target amplification and cleavage of Cas proteins. To overcome these constraints, researchers have encouragingly developed diverse strategies for precisely adjusting the cleavage activity of the CRISPR/Cas system. This review systematically summarizes advancements across six major strategies, including protein engineering, crRNA engineering, activator engineering, reporter engineering, the influence of metal ions and small molecules, and aggregation-mediated enhancement. These approaches either enhance cleavage efficiency for amplification-free, ultrasensitive detection, or temporarily suppress the cleavage activity to coordinate kinetics in integrated one-pot systems. Furthermore, future perspectives are discussed, which will contribute to the development of cleavage activity adjustment of the CRISPR/Cas system, providing insights for next-generation diagnostic technologies.

PMID 42876087
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PubMedCell death & disease2026-10-15

Mesenchymal stromal cells immunosuppress osteoarthritis synovial fluid modulated monocytes via IL-6 and CCL2.

Rasti Mozhgan M, Barazandeh Aida Feiz AF, Nouri Shahrzad S, Robb Kevin P KP et al.

Mesenchymal stromal cell (MSC) interactions with monocytes/macrophages are central to their therapeutic effects in knee osteoarthritis (KOA); however, mechanisms of these interactions are not fully understood. We hypothesize that MSC soluble factors, particularly interleukin-6 (IL-6) and C-C motif chemokine ligand (CCL2) modulate monocytes in KOA environment. Using healthy donor CD14+ monocytes exposed to KOA synovial fluid (SF) in the presence or absence of marrow-derived MSC(M) directly or conditioned medium (CM), we evaluated cell surface markers and signaling via signal transducer and activator of transcription (STAT3), nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) and c-Jun Terminal Kinase (JNK); functional responses were measured by secretion of tumor necrosis factor (TNF) and IL-1, and by phagocytosis of pHrodo Red E-coli. CD14+ monocytes demonstrated a mixed phenotype in KOA SF with increased CD163, CD206, and unchanged HLA-DR, CD86 marker expression. This was accompanied by activated STAT3, JNK, and NF-κB signaling. TNF and IL-1 secreted levels were unchanged, but phagocytosis was impaired, indicative of a net dysfunctional repair phenotype and functionality. CD14+ monocytes in KOA SF were hyporesponsive to additional lipopolysaccharide re-challenge, based on TNF and IL-1 secretion. Addition of MSC(M) to KOA SF programmed CD14+ monocytes resolved the dysfunctional phenotype and functionality, with significant increases in CD163, CD206; significant reductions in HLA-DR and CD86 expression; this was accompanied by significantly increased activated STAT3 and decreased activated JNK and NF-κB. TNF and IL-1 secretion were also significantly reduced, and phagocytic capacity restored. Blocking IL-6, or to a lesser extent, CCL2, partially abrogated MSC(M) soluble factor effects. MSC(M) experienced apoptosis in KOA SF; however, apoptotic bodies did not fully recapitulate MSC(M) soluble factor effects. IL-6, CCL2, other soluble factors and apoptotic bodies from MSC(M) secretome mitigate the dysfunctional effects of KOA SF on CD14+ monocytes resulting in immunosuppressed phenotype and functionality.

PMID 42875435
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PubMedFrontiers in aging neuroscience2026-10-15

Electroacupuncture inhibits pyroptosis to improve motor function in an MPTP-induced mouse model of Parkinson's disease.

Ying Yu-Chen YC, Dong Yi-Yue YY, Chen Guang-Yan GY, Wang Xi X et al.

To investigate whether electroacupuncture (EA) ameliorates motor dysfunction and protects nigrostriatal dopaminergic neurons in Parkinson's disease (PD) mice by inhibiting NLRP3 inflammasome-mediated pyroptosis. Male C57BL/6 mice were randomly assigned before model induction to seven groups: saline-treated control, MPTP model, MPTP plus EA, MPTP plus Nigericin, MPTP plus EA and Nigericin, MPTP plus MCC950, and MPTP plus EA and MCC950 groups. Mice in the control group received equal-volume saline, whereas mice in the other six groups were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 30 mg/kg, intraperitoneally) once daily for five consecutive days. Following model induction, EA was applied at Baihui (GV20) and Dazhui (GV14) at 100 Hz for 20 min per session over 14 days. Nigericin and MCC950 were used as an NLRP3 inflammasome activator and inhibitor, respectively. Motor function was assessed using the open-field and pole tests. Dopaminergic neuronal integrity, neuronal injury, microglial activation, and the cellular localization of NLRP3 were evaluated using immunohistochemistry, hematoxylin-eosin staining, and immunofluorescence. The expression levels of tyrosine hydroxylase, NLRP3, ASC, Caspase-1, and the N-terminal fragment of gasdermin D (GSDMD-N) were determined using immunofluorescence and western blotting. EA alleviated abnormal open-field hyperlocomotion and prolonged pole-descent latency in MPTP-treated mice, preserved tyrosine hydroxylase-positive dopaminergic neurons in the substantia nigra, restored striatal tyrosine hydroxylase expression, and reduced neuronal injury and microglial activation. NLRP3 was predominantly colocalized with tyrosine hydroxylase-positive dopaminergic neurons, whereas limited colocalization was observed with IBA-1-positive microglia. Electroacupuncture significantly suppressed the MPTP-induced upregulation of NLRP3, ASC, Caspase-1, and GSDMD-N. Nigericin exacerbated motor abnormalities, nigrostriatal injury, and pyroptosis-related signaling and largely abolished the protective effects of EA. Conversely, MCC950 produced protective effects comparable to those of EA, whereas their combined administration provided no significant additional benefit. EA improves motor dysfunction and protects the nigrostriatal dopaminergic system in MPTP-induced PD mice, at least partly by suppressing NLRP3 inflammasome-mediated pyroptosis in dopaminergic neurons. These findings identify the NLRP3 inflammasome as an important mechanistic target underlying the neuroprotective effects of electroacupuncture in experimental PD.

PMID 42876728
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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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PubMedFrontiers in endocrinology2026-10-14

Venous thromboembolism in Cushing syndrome: current evidence and a practical thromboprophylaxis algorithm.

Kuca Paweł P, Kostrzewska Paulina P, Migda Bartosz B, Witek Przemysław P

Cushing syndrome (CS) is a rare endocrine disorder associated with a markedly increased risk of venous thromboembolism (VTE). Chronic hypercortisolism induces a prothrombotic state through activation of coagulation pathways, impaired fibrinolysis, and endothelial dysfunction. VTE represents a major source of morbidity and mortality in this population, yet optimal strategies for prevention and treatment remain insufficiently standardized. To summarize current evidence on the epidemiology, pathophysiology, risk factors, prevention, and treatment of VTE in patients with endogenous CS and to propose a practical thromboprophylaxis approach. A narrative review of the literature was conducted using MEDLINE/PubMed, Scopus, and Embase databases. Observational studies, registry data, systematic reviews, and expert consensus statements addressing VTE in CS were analyzed, with particular attention to peri-operative risk and persistence of hypercoagulability after remission. Patients with CS have a 10-20-fold higher risk of VTE compared with the general population. The peri-operative period, especially after TSS or adrenalectomy, represents the highest-risk phase, although increased thrombotic risk may persist for 3-6 months after biochemical remission. Key mechanisms include elevated factor VIII, von Willebrand factor, plasminogen activator inhibitor-1, increased thrombin generation, and endothelial dysfunction. Recent evidence from the ERCUSYN registry and the 2025 Delphi consensus supports early and extended thromboprophylaxis. Current expert consensus supports low-molecular-weight heparin as the preferred peri-operative pharmacological agent, whereas direct oral anticoagulants may be considered in selected patients during long-term management. CS should be regarded as a persistent prothrombotic condition in which early and, when appropriate, extended thromboprophylaxis should be considered following individualized assessment of thrombotic and bleeding risk. Prospective studies are needed to develop evidence-based, individualized prevention strategies.

PMID 42871704
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