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 systems biology2026-11-11

From telomere dysfunction to seno-antigen selection: a conceptual framework and route-specific evidence appraisal for senolytic immunotherapy.

Niazi Sarfaraz K SK

Cellular senescence causally contributes to age-related and chronic diseases, rendering the targeted immune clearance of pathological senescent cells a promising therapeutic avenue. Progress remains limited by heterogeneity across cell lineages, tissues, inducing stressors, and temporal factors. As antigen expression alone does not ensure immune accessibility, functional recognition, or safety for healthy tissues, these aspects warrant thorough evaluation. A conceptual framework is proposed, distinct from a validated or implementable algorithm, for identifying and prioritizing senescence-associated antigens. This framework requires four criteria that a single candidate antigen must meet within the same cellular context: persistent pathological senescence, immune accessibility via a confirmed surface antigen or naturally presented human leukocyte antigen (HLA) peptide, modality-appropriate functional immune recognition, and exclusion from vital healthy or beneficially senescent states. The mechanistic origin, such as telomere dysfunction, serves as an optional stratification axis that defines coherent subsets rather than a universal prerequisite; data lacking matched telomere and antigen information in the same cells remain unverified. The process distinguishes target nomination from product validation: evidence of recognition in a single modality, such as chimeric antigen receptor (CAR) targeting of a surface antigen, does not confirm validation for alternatives like peptide vaccines. Application of the framework to urokinase-type plasminogen activator receptor (uPAR) and glycoprotein nonmetastatic melanoma protein B (GPNMB) indicates that neither candidate currently meets all criteria, and the telomere axis remains untested for both. Given that multivalent vaccination elicits immunity against each component independently, combining candidates that fail individual criteria risks amplifying liabilities rather than ensuring intersectional specificity. This outcome would require an engineered AND-gated recognition system, where the capitalized operators AND, OR, and NOT denote Boolean logic gates rather than emphasis. The framework remains in the validation phase. Each criterion receives an ordinal grade, a non-compensatory decision rule, a route-specific ligand-density window that sets the quantitative condition for recognition and healthy-cell sparing, and a predefined seven-compartment counter-screening panel. Recognition architectures are formally compared, and a pre-registered benchmarking study with specified falsification criteria is outlined as the framework's validation test.

PMID 43011401
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PubMedAnalytical chemistry2026-11-11

Modular Cell-Surface-to-Solution CRISPR-Cas12a Platform for Wash-Free Quantification of Cell-Surface Proteins on Living Cells.

Hou Xiao-Yun XY, Li Man-Ying MY, Sun Wen-Bo WB, Wu Shun-Li SL et al.

Cell-surface proteins are important biomarkers for cell phenotyping, disease diagnosis, therapeutic evaluation, and drug screening. However, their quantitative analysis on intact living cells remains challenging because conventional methods often require cell lysis, fixation, repeated washing, extensive sample processing, or bulky instrumentation. Herein, we developed a modular and reconfigurable cell-surface-to-solution CRISPR-Cas12a platform for wash-free quantitative analysis of cell-surface proteins on intact living cells. Aptamer recognition of extracellularly accessible targets deblocks a DNA activator, thereby activating Cas12a trans-cleavage in solution and converting localized cell-surface recognition into amplified fluorescence while maintaining a low background in the absence of targets. Using EpCAM as a model target, we engineered a split dual-aptamer architecture that enabled cooperative target recognition, efficient activator deblocking, and low-background signal amplification. The platform achieved sensitive EpCAM detection with a limit of detection of 32 fM and enabled live-cell analysis down to 2 cells/μL. It distinguished cell populations with different surface EpCAM levels and quantitatively monitored epithelial-mesenchymal transition-associated changes in cell-surface EpCAM abundance. Coordinated redesign of the target-responsive nucleic acid components extended the platform to PTK7 detection and the analysis of drug-induced cell-surface PTK7 remodeling. Coupling the system to a lateral flow readout enabled portable visual detection. This work establishes a modular and reconfigurable CRISPR-Cas12a sensing strategy for wash-free amplified quantification of cell-surface proteins on living cells, providing a convenient tool for investigating their dynamic remodeling during physiological and pathological processes and therapeutic responses, as well as for drug screening.

PMID 43010518
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PubMedFood science & nutrition2026-11-11

Andrographolide, A Plant-Based Dietary Bioactive Nutritional Health Compound, Attenuates Hyperoxia-Induced Acute Lung Injury by Inhibiting Ferroptosis Through the STAT3/P53 Signaling Pathway.

Xia Qiuyuan Q, Liu Xinxin X, Qin Song S, Feng Banghai B et al.

Andrographolide (AG) is a plant-derived bioactive diterpenoid compound with potential applications in nutritional science and clinical nutrition. This study investigated whether AG attenuates hyperoxia-induced acute lung injury (HALI) by inhibiting ferroptosis via the signal transducer and activator of transcription 3 (STAT3)/tumor protein P53 (P53) signaling pathway. Male C57BL/6 mice were used to establish a hyperoxia-induced lung injury model, and the protective effects of AG were compared with those of the ferroptosis inhibitor ferrostatin-1 (Fer-1). Lung histopathological changes, the lung wet-to-dry (W/D) weight ratio, reactive oxygen species (ROS), ferrous iron (Fe2+), glutathione (GSH), inflammatory cytokines, and glutathione peroxidase 4 (GPX4) expression were assessed. Network pharmacology and functional enrichment analyses were performed to identify potential targets of AG, followed by validation in MLE-12 lung epithelial cells and mouse models. Cell viability was assessed using the CCK-8 assay, and the expression of phosphorylated STAT3 (P-STAT3), total STAT3, P53, and GPX4 was examined by western blotting. Co-immunoprecipitation (Co-IP) was used to investigate the interaction between STAT3 and P53. Hyperoxia induced marked lung injury, inflammatory cell infiltration, increased pulmonary edema, and alterations in ferroptosis-related indicators. Both AG and Fer-1 attenuated lung injury and reduced ferroptosis-associated changes. Network pharmacology analysis identified 79 potential targets associated with HALI, with STAT3 emerging as a core candidate target. In MLE-12 cells, AG attenuated ferroptosis-associated changes, whereas the STAT3 phosphorylation activator Colivelin TFA attenuated these protective effects. Co-IP confirmed an interaction between STAT3 and P53, and Colivelin TFA also weakened the protective effects of AG in the mouse model. These findings suggest that AG may alleviate HALI by inhibiting ferroptosis through modulation of the STAT3/P53 signaling pathway, providing experimental evidence for its potential as a plant-derived bioactive compound for further investigation in hyperoxia-induced lung injury.

PMID 43011549
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PubMedPediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies2026-11-11

The Serum Proteomic Signatures Associated With Organ Dysfunction Based on Phoenix Criteria in Pediatric Sepsis: A Pilot Study.

Miao Huijie H, Wu Dan D, Cui Yun Y, Sun Hong H et al.

To investigate the serum proteomic characteristics linked to sepsis-induced organ dysfunction, as defined by the Phoenix Pediatric Sepsis (PPS) criteria. We conducted a serum proteomic study using data-independent acquisition mass spectrometry in pediatric patients with sepsis, admitted to the PICU at a tertiary, university-affiliated children's hospital in China. Thirty-eight patients with sepsis and 19 healthy controls were included from November 2020 to June 2022. None. A total of 403 differentially expressed proteins (DEPs) were identified in the serum of pediatric sepsis patients compared with healthy controls. Gene Set Enrichment Analysis revealed that DEPs across the four PPS-defined organ dysfunction were enriched in the antimicrobial humoral response, negative regulation of inflammation, plasminogen activation, and cytokine-mediated signaling pathways. Weighted Gene Co-Expression Network Analysis (WGCNA) showed that the MEgreen module was highly associated with the PPS score and was enriched in neutrophils. Further analysis identified seven hub proteins (tissue inhibitor of metalloproteinase-1 [TIMP1], cathepsin L peptidase 1, β-1,4-galactosyltransferase 1, carbonic anhydrase 3, interleukin 1 receptor like 1, olfactomedin 4, and cathepsin G [CATG]) as candidate serum proteomic markers of organ dysfunction risk. We used the expression of these seven hub proteins in a least absolute shrinkage and selection operator regression model to predict organ system dysfunction. It achieved an area under the curve of 0.857 for the coagulation system and 0.769 for the cardiovascular system. All seven hub proteins were significantly correlated with lactic acid and the international normalized ratio (all p < 0.05); CATG was positively correlated with mean arterial pressure (p = 0.005), TIMP1 displayed a positive correlation with d-dimer (p = 0.021) and a negative correlation with platelet (p = 0.005). We identified seven hub proteins that constitute a novel proteomic signature for predicting sepsis-associated organ dysfunction based on the Phoenix criteria. It is particularly relevant to the coagulation and cardiovascular systems.

PMID 43012616
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PubMedPlant, cell & environment2026-11-11

MdMYB1R1 Activates MdMAPKKK18 and Additional Defense Pathways to Confer Resistance to Woody Fungal Pathogens in Apple.

Liu Hailong H, Chen Shasha S, Zhang Qiyue Q, Du Yiyao Y et al.

Trunk diseases caused by woody plant pathogens, including Valsa mali and Botryosphaeria dothidea, represent a major threat to global apple production; however, the molecular basis of host resistance remains largely elusive. In this study, we employed TMT-based quantitative proteomic profiling to compare necrotic and uninfected twig tissues of apple following V. mali inoculation, identifying 904 differentially expressed proteins (DEPs). Among these, the MYB transcription factor, MdMYB1R1, exhibited a pronounced induction in response to pathogen infection. Subcellular localization and transactivation assays revealed that MdMYB1R1 localizes to the nucleus and acts as a transcriptional activator. Transient overexpression of MdMYB1R1 in Nicotiana benthamiana potentiated reactive oxygen species (ROS) accumulation and activated MAPK signaling, correlating with enhanced resistance against Sclerotinia sclerotiorum. Stable overexpression of MdMYB1R1 in apple markedly enhanced resistance to both V. mali and B. dothidea, whereas silencing of MdMYB1R1 impaired disease tolerance. Through DNA affinity purification sequencing (DAP-seq), yeast one-hybrid (Y1H), electrophoretic mobility shift assay (EMSA), and dual-luciferase reporter assays, we demonstrated that MdMYB1R1 binds to the promoter region of MdMAPKKK18 and activates its transcription, a gene encoding a mitogen-activated protein kinase kinase kinase involved in MAPK signaling. Genetic epistasis analysis further revealed that overexpression of MdMAPKKK18 only partially rescued the compromised resistance in MdMYB1R1-RNAi plants. Collectively, our findings identify MdMYB1R1 as a key positive regulator of apple resistance against trunk fungal diseases, acting at least in part by directly activating the MdMAPKKK18-mediated MAPK cascade and by regulating additional defense pathways, thus providing a promising candidate for breeding disease-resistant apple cultivars.

PMID 43010627
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PubMedFrontiers in oncology2026-11-11

Exploring the potential mechanism of artemisinin against gastric cancer based on network pharmacology, machine learning and experimental validation.

Hu Chenchen C, Zhao Yu Y, Yun Minghui M, Shen Yu Y et al.

Artemisinin, a natural active component extracted from Artemisia annua, exhibits potential anti-gastric cancer activity; however, its specific targets and molecular mechanisms remain unclear. Network pharmacology was used to predict the potential targets of artemisinin. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were performed to identify gastric cancer-related genes. Candidate targets of artemisinin against gastric cancer were obtained by intersecting the above datasets. Three machine learning algorithms, namely random forest, LASSO regression, and SVM-RFE, were further employed to screen hub targets, followed by molecular docking to evaluate the binding affinity between artemisinin and the hub targets. Finally, anti-gastric cancer effects and mechanisms were validated by in vitro experiments (CCK-8, EdU, colony formation, Transwell and Western blot). A total of 27 candidate targets of artemisinin against gastric cancer were identified. Cross-screening by the three machine learning algorithms ultimately identified TOP2A, CCNB2, and CCNA2 as hub targets. Molecular docking revealed low binding energies (all below -5.0 kcal/mol) between artemisinin and these three targets, suggesting potential binding affinity. In vitro experiments demonstrated that artemisinin significantly downregulated the mRNA expression levels of the three targets and suppressed the proliferation, migration, and invasion of gastric cancer cells. Mechanistic investigation showed that artemisinin treatment decreased p-ERK levels, and the anti-gastric cancer effects of artemisinin were partially reversed by the ERK pathway activator C16-PAF. In vitro, artemisinin suppresses ERK/MAPK pathway activation and reduces the mRNA expression of cell cycle-related TOP2A, CCNB2 and CCNA2, leading to inhibited proliferation, migration and invasion of gastric cancer cells.

PMID 43010992
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