Last update 01 Nov 2024

PLG x prothrombin x uPA

Last update 01 Nov 2024

Basic Info

Related Targets

PLGprothrombinuPA

Drugs associated with PLG x prothrombin x uPA

Recombinant staphylokinase-hirudin fusion protein(Academy of Military Medical Sciences)

Target

PLG x prothrombin x uPA

Mechanism

PLG stimulants [+2]

Active Org.-

Originator Org.

Academy of Military Medical Sciences

Active Indication-

Inactive Indication

Thromboembolism

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PLG x prothrombin x uPA

100 Translational Medicine associated with PLG x prothrombin x uPA

0 Patents (Medical) associated with PLG x prothrombin x uPA

103

Literatures (Medical) associated with PLG x prothrombin x uPA

01 Aug 2024·Anticancer Research

Transcriptional Induction ofSERPINE1and Fibrinolysis Inhibition as Predominant Effects of Glucocorticoids on the Cancer Coagulome

Article

Author: Galmiche, Antoine ; Saidak, Zuzana ; Demagny, Julien ; Godin, Corinne ; Racine, Floriane ; Louandre, Christophe

BACKGROUND/AIMHow tumors regulate the genes of the coagulome is crucial for cancer-associated thrombosis and the occurrence of venous thromboembolic complications in patients with cancer. We have previously reported potent yet complex effects of glucocorticoids (GC) on the expression of three genes that play a key role in the regulation of thrombin/plasmin activation (F3, PLAU, and SERPINE1). This study aimed to extend the investigation of GC effects to the whole tumor coagulome and assess the resulting impact on the ability of cancer cells to activate thrombin and plasmin.MATERIALS AND METHODSCancer RNA expression data were retrieved from various sources. Additionally, oral squamous cell carcinoma (OSCC) cells exposed to GC in vitro were analyzed using QPCR, enzymatic assays measuring thrombin and urokinase-type Plasminogen Activator (uPA) activity, and D-dimer concentrations.RESULTSOur findings highlight the potent and specific stimulatory effect of GC on SERPINE1 expression across different types of cancer. Consistently, GC were found to inhibit uPA proteolytic activity and reduce the concentrations of D-dimers in OSCC in vitro.CONCLUSIONFibrinolysis inhibition is a key consequence of cancer cell exposure to GC, possibly leading to the stabilization of the fibrin clot in cancer.

26 Jan 2022·ACS Applied Materials & InterfacesQ2 · MATERIALS SCIENCE

Bioresponsive Polyphenol-Based Nanoparticles as Thrombolytic Drug Carriers

Q2 · MATERIALS SCIENCE

Article

Author: Wang, Ting-Yi ; Lin, Zhixing ; Hagemeyer, Christoph E. ; Caruso, Frank ; Hu, Yingjie ; Ju, Yi ; Palazzolo, Jason S. ; Niego, Be’eri ; Pan, Shuaijun ; Zhou, Jiajing ; Yu, Haitao

Thrombolytic (clot-busting) therapies with plasminogen activators (PAs) are first-line treatments against acute thrombosis and ischemic stroke. However, limitations such as narrow therapeutic windows, low success rates, and bleeding complications hinder their clinical use. Drug-loaded polyphenol-based nanoparticles (NPs) could address these shortfalls by delivering a more targeted and safer thrombolysis, coupled with advantages such as improved biocompatibility and higher stability in vivo. Herein, a template-mediated polyphenol-based supramolecular assembly strategy is used to prepare nanocarriers of thrombolytic drugs. A thrombin-dependent drug release mechanism is integrated using tannic acid (TA) to cross-link urokinase-type PA (uPA) and a thrombin-cleavable peptide on a sacrificial mesoporous silica template via noncovalent interactions. Following drug loading and template removal, the resulting NPs retain active uPA and demonstrate enhanced plasminogen activation in the presence of thrombin (1.14-fold; p < 0.05). Additionally, they display lower association with macrophage (RAW 264.7) and monocytic (THP-1) cell lines (43 and 7% reduction, respectively), reduced hepatic accumulation, and delayed blood clearance in vivo (90% clearance at 60 min vs 5 min) compared with the template-containing NPs. Our thrombin-responsive, polyphenol-based NPs represent a promising platform for advanced drug delivery applications, with potential to improve thrombolytic therapies.

01 Nov 2021·Current NeuropharmacologyQ2 · MEDICINE

Serine Proteases and Chemokines in Neurotrauma: New Targets for Immune Modulating Therapeutics in Spinal Cord Injury

Q2 · MEDICINE

Review

Author: Varkoly, Kyle S. ; Burgin, Michelle ; Guo, Qiuyun ; Zhang, Liqiang ; Beladi, Roxana N. ; Hogue, Ian ; Dobrowski, Wojciech ; Schutz, Lauren ; Yaron, Jordan R. ; Tierney, Wesley ; Lucas, Alexandra R.

:Progressive neurological damage after brain or spinal cord trauma causes loss of motor function and treatment is very limited. Clotting and hemorrhage occur early after spinal cord (SCI) and traumatic brain injury (TBI), inducing aggressive immune cell activation and progressive neuronal damage. Thrombotic and thrombolytic proteases have direct effects on neurons and glia, both healing and also damaging bidirectional immune cell interactions. Serine proteases in the thrombolytic cascade, tissue- and urokinase-type plasminogen activators (tPA and uPA), as well as the clotting factor thrombin, have varied effects, increasing neuron and glial cell growth and migration (tPA), or conversely causing apoptosis (thrombin) and activating inflammatory cell responses. tPA and uPA activate plasmin and matrix metalloproteinases (MMPs) that break down connective tissue allowing immune cell invasion, promoting neurite outgrowth. Serine proteases also activate chemokines. Chemokines are small proteins that direct immune cell invasion but also mediate neuron and glial cell communication. We are investigating a new class of therapeutics, virus-derived immune modulators; One that targets coagulation pathway serine proteases and a second that inhibits chemokines. We have demonstrated that local infusion of these biologics after SCI reduces inflammation providing early improved motor function. Serp-1 is a Myxomavirus-derived serine protease inhibitor, a serpin, that inhibits both thrombotic and thrombolytic proteases. M-T7 is a virus-derived chemokine modulator.:Here we review the roles of thrombotic and thrombolytic serine proteases and chemoattractant proteins, chemokines, as potential therapeutic targets for SCI. We discuss virus-derived immune modulators as treatments to reduce progressive inflammation and ongoing nerve damage after SCI.

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