更新于：2024-11-01

HPSE x factor Xa

更新于：2024-11-01

基本信息

关联

项与 HPSE x factor Xa 相关的药物

EP-37161

靶点

HPSE x factor Xa

作用机制

乙酰肝素酶抑制剂 [+1]

在研机构-

原研机构

Endotis Pharma SA

在研适应症-

非在研适应症

血栓形成

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 HPSE x factor Xa 相关的临床结果

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100 项与 HPSE x factor Xa 相关的转化医学

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0 项与 HPSE x factor Xa 相关的专利（医药）

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项与 HPSE x factor Xa 相关的文献（医药）

2023-09-21·World journal of gastroenterology

Heparanase inhibition leads to improvement in patients with acute gastrointestinal injuries induced by sepsis.

作者: Liu, Li-Ping ; Chen, Ting-Ting ; Lv, Jia-Jun ; Chen, Ling ; Li, Min

BACKGROUNDPatients with sepsis are at high risk for acute gastrointestinal injury (AGI), but the diagnosis and treatment of AGI due to sepsis are unsatisfactory. Heparanase (HPA) plays an important role in septic AGI (S-AGI), but its specific mechanism is not completely understood, and few clinical reports are available.AIMTo explore the effect and mechanism of HPA inhibition in S-AGI patients.METHODSIn our prospective clinical trial, 48 patients with S-AGI were randomly assigned to a control group to receive conventional treatment, whereas 47 patients were randomly assigned to an intervention group to receive conventional treatment combined with low molecular weight heparin. AGI grade, sequential organ failure assessment score, acute physiology and chronic health evaluation II score, D-dimer, activated partial thromboplastin time (APTT), anti-Xa factor, interleukin-6, tumour necrosis factor-α, HPA, syndecan-1 (SDC-1), LC3B (autophagy marker), intestinal fatty acid binding protein, D-lactate, motilin, gastrin, CD4/CD8, length of intensive care unit (ICU) stay, length of hospital stay and 28-d survival on the 1^st, 3^rd and 7^th d after treatment were compared. Correlations between HPA and AGI grading as well as LC3B were compared. Receiver operator characteristic (ROC) curves were generated to evaluate the diagnostic value of HPA, intestinal fatty acid binding protein and D-lactate in S-AGI.RESULTSSerum HPA and SCD-1 levels were significantly reduced in the intervention group compared with the control group (P < 0.05). In addition, intestinal fatty acid-binding protein, D-lactate, AGI grade, motilin, and gastrin levels and sequential organ failure assessment score were significantly decreased (P < 0.05) in the intervention group. However, LC3B, APTT, anti-Xa factor, and CD4/CD8 were significantly increased (P < 0.05) in the intervention group. No significant differences in interleukin-6, tumour necrosis factor-α, d-dimer, acute physiology and chronic health evaluation II score, length of ICU stay, length of hospital stay, or 28-d survival were noted between the two groups (P > 0.05). Correlation analysis revealed a significant negative correlation between HPA and LC3B and a significant positive correlation between HPA and AGI grade. ROC curve analysis showed that HPA had higher specificity and sensitivity in diagnosis of S-AGI.CONCLUSIONHPA has great potential as a diagnostic marker for S-AGI. Inhibition of HPA activity reduces SDC-1 shedding and alleviates S-AGI symptoms. The inhibitory effect of HPA in gastrointestinal protection may be achieved by enhanced autophagy.

2022-11-01·Carbohydrate Polymers

Enzymatic synthesis of low molecular weight heparins from N-sulfo heparosan depolymerized by heparanase or heparin lyase

Article

作者: Yu, Yanlei ; Varghese, Sony ; Fu, Li ; Wang, Hong ; Dordick, Jonathan ; Xia, Ke ; Linhardt, Robert J ; Zhang, Fuming ; He, Peng

Low-molecular-weight heparin (LMWH) is prepared from the controlled chemical or enzymatic depolymerization of animal sourced heparins. It has been widely used as an anticoagulant. Concerns about the shortcomings of animal-derived heparin and the contamination of supply chain demand biochemical approaches for synthesizing LMWH. In the present study, two LMWHs were enzymatically synthesized from low molecular weight N-sulfated heparosan (LMW-NSH) cleaved by recombinant hydrolase, endo-β-glucuronidase, (HepBp) or heparin lyase III (HepIII), followed by subsequent sulfotransferase modifications. Structural characterization shows that LMWH chains prepared using HepBp had a saturated uronic acid residue at their reducing ends, while chains of LMWH prepared using HepIII had an unsaturated uronic acid residue at their non-reducing end. Both LMWHs had anti-factor Xa and anti-factor IIa activities comparable to enoxaparin. This approach demonstrates that the hydrolase, HepBp, can be used to prepare a new type of LMWH that has no unsaturated uronic acid at its non-reducing end.

2020-02-01·Thorax1区 · 医学

Heparan sulfate chains contribute to the anticoagulant milieu in malignant pleural effusion

1区 · 医学

Article

作者: Attias, Judith ; Hardak, Emilia ; Peled, Eli ; Nadir, Yona ; Asayag, Keren ; Ghanem, Shourouk ; Kogan, Inna ; Crispel, Yonatan

BackgroundWhile malignant pleural effusion (MPE) is a common and significant cause of morbidity in patients with cancer, current treatment options are limited. Human heparanase, involved in angiogenesis and metastasis, cleaves heparan sulfate (HS) side chains on the cell surface.AimsTo explore the coagulation milieu in MPE and infectious pleural effusion (IPE) focusing on the involvement of heparanase.MethodsSamples of 30 patients with MPE and 44 patients with IPE were evaluated in comparison to those of 33 patients with transudate pleural effusions, using heparanase ELISA, heparanase procoagulant activity assay, thrombin and factor Xa chromogenic assays and thromboelastography. A cell proliferation assay was performed. EMT-6 breast cancer cells were injected to the pleural cavity of mice. A peptide inhibiting heparanase activity was administered subcutaneously.ResultsLevels of heparanase, factor Xa and thrombin were significantly higher in exudate than transudate. Thromboelastography detected almost no thrombus formation in the whole blood, mainly on MPE addition. This effect was completely reversed by bacterial heparinase. Direct measurement revealed high levels of HS chains in pleural effusions. Higher proliferation was observed in tumour cell lines incubated with exudate than with transudate and it was reduced when bacterial heparinase was added. The tumour size in the pleural cavity of mice treated with the heparanase inhibitor were significantly smaller compared with control (p=0.005).ConclusionsHS chains released by heparanase form an anticoagulant milieu in MPE, preventing local thrombosis and enabling tumour cell proliferation. Inhibition of heparanase might provide a therapeutic option for patients with recurrent MPE.