Last update 01 Nov 2024

Serine protease x uPA

Last update 01 Nov 2024

Basic Info

Related Targets

Serine proteaseuPA

Drugs associated with Serine protease x uPA

VT-111

Target

Serine protease x uPA

Mechanism

Serine protease inhibitors [+1]

Active Org.-

Originator Org.

Viron Therapeutics, Inc.

Active Indication-

Inactive Indication

Acute Coronary Syndrome [+8]

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with Serine protease x uPA

NCT00243308 / TerminatedPhase 2

A Phase 2, Multicentre, Double-Blind, Placebo-Controlled, Dose Escalating Trial of the Safety, Pharmacokinetics, and Biological Activity of 3 Consecutive Daily Doses of Serp-1 When Added to Conventional Therapy in Patients With Acute Coronary Syndromes (Non ST-Elevation Myocardial Infarction and/or Unstable Angina)

Males and females aged 18-80 years who present with ACS (unstable angina and non ST-elevation MI) defined as one or more episodes of angina lasting at least 5 minutes in the last 24 hours before admission and greater than 0.05 mV of presumed new ST-segment depression in at least 2 contiguous ECG leads OR, angina and per confirmatory angiogram, has been scheduled for percutaneous coronary angioplasty. The primary objective of this study is to evaluate the safety of Serp-1 injection when administered in 3 daily doses to patients undergoing conventional therapy for Acute Coronary Syndrome (ACS) requiring early intervention.

Start Date01 Oct 2005

Sponsor / Collaborator

Viron Therapeutics, Inc.

100 Clinical Results associated with Serine protease x uPA

100 Translational Medicine associated with Serine protease x uPA

0 Patents (Medical) associated with Serine protease x uPA

372

Literatures (Medical) associated with Serine protease x uPA

01 Aug 2024·American Journal of Reproductive Immunology

Characterization of Inflammation/Immune‐, Acute Phase‐, Extracellular Matrix‐, Adhesion‐, and Serine Protease‐Related Proteins in the Amniotic Fluid of Women With Early Preterm Prelabor Rupture of Membranes

Article

Author: Lee, Kyong‐No ; Kim, Hyeon Ji ; Choi, Bo Young ; Lee, Min Jung ; Park, Kyo Hoon ; Cho, Iseop

ABSTRACTProblemTo determine whether altered concentrations of various inflammation/immune‐, acute phase‐, extracellular matrix‐, adhesion‐, and serine protease‐related proteins in the amniotic fluid (AF) are independently associated with microbial invasion of the amniotic cavity and/or intra‐amniotic inflammation (MIAC/IAI), imminent spontaneous preterm delivery (SPTD; ≤7 days), and major neonatal morbidity/mortality (NMM) in women with early preterm prelabor rupture of membranes (PPROM).Method of StudyThis was a retrospective cohort study involving 111 singleton pregnant women with PPROM (24–31 weeks) undergoing amniocentesis to diagnose MIAC/IAI. The following proteins were measured in stored AF samples by enzyme‐linked immunosorbent assay (ELISA): APRIL, DKK‐3, Gal‐3BP, IGFBP‐2, IL‐8, VDBP, lumican, MMP‐2, MMP‐8, SPARC, TGFBI, TGF‐β1, E‐selectin, ICAM‐5, P‐selectin, haptoglobin, hepcidin, SAA1, kallistatin, and uPA.ResultsMultivariate logistic regression analyses revealed that (i) elevated APRIL, IL‐8, MMP‐8, and TGFBI levels in the AF, reduced lumican and SPARC levels in the AF, and high percentages of samples above the lower limit of quantification for AF TGF‐β1 and uPA were significantly associated with MIAC/IAI; (ii) elevated AF levels of IL‐8 and MMP‐8 were significantly associated with SPTD within 7 days; and (iii) elevated AF IL‐6 levels were significantly associated with increased risk for major NMM, when adjusted for baseline covariates.ConclusionECM (lumican, SPRAC, TGFBI, and TGF‐β1)‐ and serine protease (uPA)‐associated proteins in the AF are involved in the regulation of the host response to infection/inflammation in the amniotic cavity, whereas AF inflammation (IL‐8, MMP‐8, and IL‐6)‐associated mediators are implicated in the development of preterm parturition and major NMM in early PPROM.

04 Jun 2024·Biochemistry

The Light Chain Allosterically Enhances the Protease Activity of Murine Urokinase-Type Plasminogen Activator

Article

Author: Engelberger, Felipe ; Ramírez-Sarmiento, César A. ; Torres-Paris, Constanza ; Komives, Elizabeth A. ; Song, Harriet J.

The active form of the murine urokinase-type plasminogen activator (muPA) is formed by a 27-residue disordered light chain connecting the amino-terminal fragment (ATF) with the serine protease domain. The two chains are tethered by a disulfide bond between C1_CT in the disordered light chain and C122_CT in the protease domain. Previous work showed that the presence of the disordered light chain affected the inhibition of the protease domain by antibodies. Here we show that the disordered light chain induced a 3.7-fold increase in k_cat of the protease domain of muPA. In addition, hydrogen-deuterium exchange mass spectrometry (HDX-MS) and accelerated molecular dynamics (AMD) were performed to identify the interactions between the disordered light chain and the protease domain. HDX-MS revealed that the light chain is contacting the 110s, the turn between the β10- and β11-strand, and the β7-strand. A reduction in deuterium uptake was also observed in the activation loop, the 140s loop and the 220s loop, which forms the S1-specificty pocket where the substrate binds. These loops are further away from where the light chain seems to be interacting with the protease domain. Our results suggest that the light chain most likely increases the activity of muPA by allosterically favoring conformations in which the specificity pocket is formed. We propose a model by which the allostery would be transmitted through the β-strands of the β-barrels to the loops on the other side of the protease domain.

01 Feb 2024·Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

Pan-cancer analysis of PLAU indicates its potential prognostic value and correlation with neutrophil infiltration in BLCA

Article

Author: Shi, Ke ; Zhou, Jianda ; Zhang, Jiaqi ; Yan, Wenguang ; Jiang, Li ; Zhang, Xiulan ; Li, Man

BACKGROUNDPLAU is known as a selected serine protease converting plasminogen to plasmin. The role of PLAU in the development of pan-cancer, especially bladder urothelial carcinoma (BLCA) remains unclear.METHODA variety of online tools and cancer databases, including TCGA, GETx, HPA database, GSCALite, UALCAN, ESTIMATE, CIBERSORT, ssGSEA algorithms and SangerBox website, were applied to investigate the associations between PLAU expression and prognosis, genetic alterations, pathway activation, and tumor immunity in pan-cancer. Through cBioPortal and STITCH platforms, the oncogenic role of PLAU and related targeting medicines in BLCA were also explored. We verified the expression of PLAU in pan-cancer cells and its function in bladder cancer cell lines using wet-lab experiments.RESULTSPLAU expression levels were significantly higher in most cancer tissues. PLAU had a certain accuracy in the diagnosis of various types of cancers (90 % AUC > 0.700). In BLCA, PLAU has abundant methylated sites and showed statistical differences in clinical features. PLAU was involved in tumor immune infiltration, and especially positively correlated with neutrophil infiltration. High-expressed PLAU indicated poorer prognosis in the BLCA patients receiving Atezolizumab. A high mRNA and protein expression levels of PLAU were observed in pan-cancer cell lines, especially BLCA cells. Knockdown of PLAU inhibited the invasive, proliferative, and aggressive phenotypes of bladder cancer cells. Immunohistochemical staining validated PLAU's higher expression in BLCA tissues than in adjacent non-cancerous tissues. And overexpression of PLAU was associated with more advanced TNM stage, and high infiltrating depth.CONCLUSIONOur study revealed that PLAU can serve as a potential therapeutic target and prognostic marker for various malignancies, especially BLCA.

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