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

PubMedMedicine2026-09-19

Exploring the potential mechanism of Xiaoqinglong Decoction in the treatment of acute exacerbations of chronic obstructive pulmonary disease based on network pharmacology and in silico study.

Yu Hongpeng H, Wei Xiaotong X, Hu Shaodan S, Ding Huan H et al.

Xiaoqinglong Decoction (XQLD) is a traditional Chinese herbal formula widely used in clinical practice to treat acute exacerbations of chronic obstructive pulmonary disease (AECOPD) with notable efficacy. Studies indicate that XQLD can effectively modulate the inflammatory response during the acute infectious phase of AECOPD; however, its underlying mechanism of action remains unclear. This study employed network pharmacology, molecular docking, and molecular dynamics simulations to investigate the potential target genes of XQLD and its possible mechanisms of action in treating AECOPD. Active ingredients and related targets of XQLD were identified from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, SwissTargetPrediction, and UniProt. AECOPD-related targets were collected from GeneCards, DrugBank, online Mendelian inheritance in man, and PharmGKB. Common targets between the active ingredients of XQLD and AECOPD were screened. A protein-protein interaction network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins database and visualized with Cytoscape. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery database. Molecular docking and molecular dynamics simulations were conducted using AutoDock Vina and GROMACS, respectively, to evaluate the binding affinity and stability between core targets and active components. The results revealed that the active ingredients of XQLD, including quercetin, luteolin, and kaempferol, target multiple genes such as nuclear factor kappa B subunit 1, signal transducer and activator of transcription 1, mechanistic target of rapamycin kinase, caspase-3, BCL2‑Like 1, and MYC, primarily through the TNF and PI3K/Akt signaling pathways. Molecular docking and dynamics simulations confirmed stable binding between core targets and active ingredients, particularly between glyuranolide and signal transducer and activator of transcription 1, which merits further investigation. XQLD may alleviate AECOPD progression by regulating the inflammatory response, hypoxia, and apoptosis through multi-component, multi-target, and multi-pathway mechanisms. These findings provide a theoretical basis for further experimental research and potential clinical application of XQLD.

PMID 42760649
Read full article →
PubMedbioRxiv : the preprint server for biology2026-09-19

Herpes simplex virus 1 subverts the mitochondrial network to support the infection: A lesson on mitochondrial versatility.

Saud Rabina R, Foster-Lemieur Kimberly K, Duguay Brett B, Swerdlow Russell R et al.

Herpes simplex virus 1 (HSV-1) infects approximately 67% of the population worldwide. It establishes lifelong reservoirs in sensory neurons and has been linked to several diseases including neuronal dysfunction. Disruption of mitochondrial homeostasis is a hallmark of HSV-1 infection, however a molecular understanding of these changes and their significance is not yet well defined. HSV-1 infection causes a UL12.5-dependent inhibition of mitochondrial biogenesis through the loss of mitochondrial DNA and mitochondrial transcription factors, PGC-1α (peroxisome proliferator-activated receptor-gamma co-activator) and TFAM (mitochondrial transcription factor). Conversely, UL12.5-independent mechanisms inhibit mitochondrial fusion by activating the OMA1 metallopeptidase that cleaves the inner mitochondrial membrane fusion protein OPA1 (optic atrophy protein 1) and by down-modulating the outer mitochondrial membrane fusion protein MFN2 (mitofusin 2). This inhibition of fusion results in a smaller mitochondrial network that clusters to perinuclear regions, likely supplying energy for viral replication and envelopment. The inner mitochondrial membrane protein TIM23 is also down-modulated during infection in a UL12.5-independent mechanism. Failure of the virus to promote these changes negatively impacts the infection. Despite these changes, mitochondria are protected from mitophagy due to the viral-induced degradation of several mitophagy adaptor proteins, whereby damaged mitochondrial components, including mitochondrial DNA, are extruded via extracellular vesicles. These mitochondrial changes still support functions necessary for HSV-1 infection. Basal cell respiration is preserved, while spare respiratory capacity and extracellular acidification rates increase, indicating glycolytic activity. Mitochondrial membrane potential is also preserved. Overall, our studies provide mechanistic insight into how HSV-1 impacts mitochondria, which could contribute to viral pathogenesis. Mitochondria are often referred to as the "powerhouse" of the cell because they are the main energy producers. Disruption of mitochondrial homeostasis is associated with multiple diseases and occurs after infection with pathogens such as HSV-1. By investigating the mechanism(s) by which HSV-1 disrupts mitochondrial homeostasis, we can better understand how HSV-1 causes pathogenesis. HSV-1 infection impacts mitochondrial homeostasis through disruption of four key processes, including: 1) inhibition of mitochondrial biogenesis and the generation of new mitochondria; 2) inhibition of mitochondrial fusion, which rescues reversibly damaged mitochondria; 3) sustaining mitochondrial fission, which removes damaged content; and 4) preventing mitophagy, which clears damaged mitochondria. UL12.5-dependent and UL12.5- independent events during HSV-1 infection disrupt mitochondrial homeostasis, redirecting mitochondrial resources towards progeny virus production. These changes cause irreversible damage to host cells, ultimately driving pathogenesis.

PMID 42760986
Read full article →
PubMedPloS one2026-09-18

L-(+)-Ergothioneine ameliorates preeclampsia-associated vascular endothelial dysfunction by modulating the Nrf2-PPARγ-sFlt-1 axis.

Gong Jingjin J, Liu Yan Y, Meng Qingju Q, Wu Junwei J et al.

Preeclampsia (PE) is a serious complication of pregnancy, with vascular endothelial dysfunction being a core pathological feature. This study aimed to investigate whether L-(+)-ergothioneine (LET) ameliorates PE-associated endothelial dysfunction by regulating the Nrf2-PPARγ-sFlt-1 axis. A LPS-induced trophoblast dysfunction model was established using lipopolysaccharide (LPS)-induced human trophoblast cells (HTR8/SVneo). Techniques including CCK-8 assay, flow cytometry, wound healing assay, ELISA, qPCR, Western blot, and immunofluorescence were employed to assess the effects of LET on cell viability, apoptosis, invasion, inflammatory cytokine levels, and the expression of key molecules in the signaling pathway. LET significantly increased the viability of LPS-induced trophoblasts, promoted migration, inhibited apoptosis, and downregulated pro-inflammatory cytokines (IL-6, TNF-α, IFN-γ) and endothelial dysfunction markers (sFlt-1, ET-1, PAI-1), while upregulating the anti-inflammatory cytokine IL-4 and plasminogen activators (tPA, uPA). Mechanistically, LET inhibited Nrf2 nuclear translocation and promoted PPARγ expression, consequently reducing sFlt-1 levels. The protective effects of LET were mimicked by the PPARγ activator pioglitazone and reversed by the inhibitor FX-909. Furthermore, the supernatant from LET-treated trophoblasts promoted the viability and invasion of human umbilical vein endothelial cells (HUVECs). L-(+)-Ergothioneine improves trophoblast function and indirectly promotes endothelial recovery by modulating the Nrf2-PPARγ-sFlt-1 axis, suggesting a potential therapeutic target for preeclampsia.

PMID 42758703
Read full article →
PubMedFrontiers in immunology2026-09-18

Decreased expression of immune activator WARS1 and other pro-inflammatory mediators in type 1-like macrophages as an associated mode of action in response to fucoidan from marine brown algae.

Ostermann Jasmin J, Gemoll Timo T, Schnüttgen Tabea T, Tischhöfer Marie-Theres MT et al.

Macrophages are key regulators of innate and adaptive immune responses through antigen presentation and the production of inflammatory mediators and growth factors. Imbalances in the activation and inhibition of pro-inflammatory type 1-like macrophages (M1) and anti-inflammatory type 2-like macrophages (M2) are closely associated with various autoimmune and chronic inflammatory diseases, underscoring the need for targeted therapeutic approaches. Numerous studies have shown that sulfated polysaccharides from marine algae, especially fucoidans from brown algae, exhibit a wide range of anti-inflammatory activities. This study aims to investigate the anti-inflammatory mode of action of algae-derived fucoidans in monocyte-derived macrophages and to identify the key regulatory proteins and inflammatory mediators involved. We applied data-independent mass spectrometry to comprehensively evaluate protein profiles of monocyte-derived M1/M2-like macrophages under the influence of sulfated polysaccharides from different algae species, namely fucoidans from the brown algae Saccharina latissima, Fucus evanescens, and Laminaria digitata, as well as the sulfated xylogalactan from the red alga Delesseria sanguinea. Furthermore, a series of gradually depolymerized fractions of the fucoidan from Saccharina latissima was investigated to elucidate the impact of molecular weight (MW) on protein expression levels and cytokine secretion patterns using membrane-based cytokine arrays and ELISA measurements. Among the tested sulfated polysaccharides, especially the fucoidan from Saccharina latissima showed anti-inflammatory effects. They significantly reduced expression levels of pro-inflammatory tryptophanyl-tRNA synthetase (WARS1), the cytokines interferon gamma-induced protein 10 (IP-10, syn. CXCL10) and macrophage migration inhibitory factor (MIF), as well as urokinase-type plasminogen activator receptor (uPAR) in pro-inflammatory M1-like macrophages, whereby their effects turned out to be independent of the MW. Our study provides novel insights into the anti-inflammatory mode of action of fucoidan from Saccharina latissimima on monocyte-derived macrophages. Further in vitro and in vivo studies are required to better understand the underlying molecular pathways, the associated mechanism and to evaluate potential medical applications.

PMID 42756851
Read full article →
PubMedNature microbiology2026-09-18

AP2-HS and a GDV1 regulatory feedback loop mediate environmental induction of sexual conversion in Plasmodium falciparum.

Tintó-Font Elisabet E, Casas-Vila Núria N, Martínez-Guardiola César C, Pérez-Cantero Alba A et al.

Human-to-mosquito transmission of the malaria parasite Plasmodium falciparum requires conversion of some parasites to gametocytes, a non-replicative sexual form. Specific conditions of the human blood environment that induce parasite stress increase sexual conversion rates. Sexual conversion is triggered by the transcription factor AP2-G and its upstream activator, GDV1. However, the molecular mechanisms underlying environmentally induced sexual conversion are unclear. Here we show that environmental induction of gdv1 expression and sexual conversion requires the transcription factor AP2-HS, which plays a dual role as activator or repressor in different pathways. Activation of gdv1 expression, either spontaneously or in response to environmental conditions, triggers a positive-negative regulatory feedback loop between GDV1 and its antisense long non-coding RNA (gdv1-as) repressor. This involves GDV1-dependent displacement of heterochromatin from the gdv1-as promoter. Our results describe a complex regulatory mechanism enabling P. falciparum to adjust its investment in transmission under different stress conditions.

PMID 42754706
Read full article →
PubMedNucleic acids research2026-09-18

Deadenylation and decapping factors cooperatively stimulate biochemical activities of DEAD-box ATPase Dhh1.

Braun Gabriel A GA, Kumar Rakesh R, Hinnebusch Alan G AG, Gross John D JD

The DEAD-box ATPase Dhh1 (DDX6 in humans) is a general activator of 5'-3' mRNA decay that acts between the deadenylation and decapping steps of the pathway, although the exact mechanism of its action remains unclear. Dhh1 has been shown to interact with the MIF4G domain of the central scaffold protein of the Ccr4-Not deadenylase complex, Not1, as well as the decapping activator Edc3. Although structures have been published of Dhh1 in complex with Not1MIF4G or an Edc3 peptide, the impact of these interactions on the catalytic cycle of Dhh1 are unknown. Here, we show that cEdc3 enhances ATP and RNA binding by Dhh1, whereas Not1MIF4G promotes the catalytic step of ATP hydrolysis. Additionally, the modulation of Dhh1 activity by Edc3 requires a more extensive set of interaction motifs and interfaces than was previously recognized. While the effect of either Not1MIF4G or Edc3 on the ATPase activity of Dhh1 is modest, together both proteins increase Dhh1 activity over 200-fold. The fact that Dhh1 biochemical activity is cooperatively tuned by deadenylation and decapping factors suggests that Dhh1 may coordinate deadenylation and decapping in the 5'-3' mRNA decay pathway through changes in its ATP-coupled RNA binding affinity during its catalytic cycle.

PMID 42755361
Read full article →

+9996 more articles available with a free account

Sign up free to view all articles →

Ask about plasminogen activator