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更新于：2025-05-07

Thrombin inhibitors(Virginia Commonwealth University)

更新于：2025-05-07

概要

概要

基本信息

药物类型

小分子化药

别名-

靶点

thrombin

作用方式

抑制剂

作用机制

thrombin抑制剂(激活型凝血因子II抑制剂)

治疗领域-

在研适应症-

非在研适应症-

原研机构

Virginia Commonwealth University

在研机构

Virginia Commonwealth University

非在研机构-

权益机构-

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

关联

100 项与 Thrombin inhibitors(Virginia Commonwealth University) 相关的临床结果

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100 项与 Thrombin inhibitors(Virginia Commonwealth University) 相关的转化医学

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100 项与 Thrombin inhibitors(Virginia Commonwealth University) 相关的专利（医药）

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1,946

项与 Thrombin inhibitors(Virginia Commonwealth University) 相关的文献（医药）

2025-05-13·Oncogene

The coagulation and tumor system are directly linked through the proteolysis and activation of epidermal growth factor receptor by thrombin

Article

作者: Yu, Min ; Zhao, Bing ; Shen, Zhiyuan ; Wang, Tianfa ; Zhang, Xiaohan ; Yu, Sanjian ; Yang, Liu

Cancer cachexia and cancer-associated thrombosis are potentially fatal outcomes of advanced cancer. Unfortunately, this knowledge has not yet led to any breakthrough in cancer therapy. Thrombin is the key enzyme of blood coagulation system. The identification of a direct link between thrombin and the tumor progression remains unknown. We illustrated thrombin expression in lung adenocarcinoma (LUAD) was closely related to clinicopathological features, prognosis, and chemotherapy outcome of patients via TCGA and clinical pathological analysis. Using genetic and pharmacological approaches, we showed a direct link between thrombin catalytic activity and lung cancer progression in vitro and in vivo. Furthermore, we revealed that thrombin cleaves epidermal growth factor receptor (EGFR) at a GRG motif perfectly conserved across disparate species, indicating functional importance, which results in activation of EGFR/AKT/mTOR signaling pathway. Last we found the mutual interaction between thrombin and chemotherapy resistance. Combination therapy of thrombin inhibitor and chemotherapy results in improved anti-tumor efficacy. Together, our data firstly revealed a mechanism of cancer progression and chemotherapy resistance that involves thrombin-mediated EGFR cleavage. We propose that thrombin could be a prognostic biomarker for lung cancer, blockade of thrombin is a valuable therapeutic strategy to overcome cancer's resistance to chemotherapy.

2025-03-12·Cureus

Dabigatran Combined With Benztropine Ameliorates Cobalt Chloride-Induced Parkinsonism in Rats, Restores Protease-Activated Receptor 1 (PAR1), and Mitigates Oxidative Stress

Article

作者: Mohamed Sayed, Walaa ; Mahmoud, Hesham M ; Elmorsy, Soha ; Sharif Ismail Negm, Mohamed ; Abdelmissih, Sherine ; Ahmed Rashed, Laila

BACKGROUNDThe presumed implication of thromboembolic and oxidative stress pathways in parkinsonism guided the current research toward the exploration of the anticoagulant dabigatran etexilate (DE) as a thrombin inhibitor in the cobalt chloride (CoCl₂)-induced parkinsonism (CIP) model, a model of significance to industrial toxins-related health issues.METHODSOral CoCl₂ (12.5 mg/kg) was administered daily for 60 days, with the introduction of benztropine mesylate (BM) (10 mg/kg) and/or DE (3 mg/kg) on day 31. Rearing, postural instability, and pasta handling were evaluated, followed by histopathologic examination of the substantia nigra (SN) and striatum (STR). The expressions of brain dopamine receptor 2 (D₂ ), adenosine receptor 1 (A₁) and 2A (A_2A), and protease-activated receptor 1 (PAR1), as well as the brain levels of dopamine (DA), endothelin 1 (ET1), malondialdehyde (MDA), and glutathione (GSH), were assessed.RESULTSBM+DE restored the number of rears to the control level, compared to being reduced in the CIP model. BM+DE restored the first, second, third, and average displacement distances to the control level, compared to being reduced in the CIP model. BM+DE was superior to either BM or DE in restoring the time to finish eating pasta and the number of adjustments of forepaws while eating to control levels after being affected in the CIP model. BM+DE restored DA to the control level and was superior to DE in restoring D₂ to the control level. BM+DE was superior to BM in restoring A₁and A_2A , increasing A₁/A_2Abeyond the control level. BM+DE was superior to BM in restoring PAR1 and ET1 to control levels. BM+DE was superior to BM in restoring MDA to the control level and was superior to both BM and DE in increasing GSH beyond the control level. BM+DE exhibited the highest percentage of preserved neurons in SN, which was negatively correlated with MDA.CONCLUSIONBM+DE offers a therapeutic potential for parkinsonism triggered by chronic exposure to CoCl₂. The implication of thrombin-related factors and oxidative stress in the modulation of the dopaminergic-adenosinergic crosstalk is plausible.

2025-03-01·Cardiology in Review

Left Atrial Appendage Closure: What Do We Know?

Review

作者: Khraisha, Ola ; Kaul, Risheek ; Wiener, Philip C. ; Frishman, William H. ; Alzubi, Jafar ; Babapoor-Farrokhran, Savalan ; Aronow, Wilbert S. ; Mainigi, Sumeet K. ; Port, Zachary ; Sooknanan, Naveen ; Farrokhran, Ali Babapour ; Rasekhi, Roozbeh Tarighati

Atrial fibrillation (AF) is the most common arrhythmia in the United States and the most common cause of embolic cerebrovascular events, with the majority of these thrombi originating in the left atrial appendage. The left atrial appendage (LAA) has separate developmental, ultrastructural, and physiological characteristics from the left atrium. Although LAA anatomy is highly variable, it can be categorized into 4 types: cactus, cauliflower, chicken wing, and windsock. The cauliflower type is associated with higher stroke risk in patients with nonvalvular AF. Although the cornerstone of therapy to prevent embolic strokes from AF has been anticoagulation with thrombin inhibitors, a large group of patients are unable to tolerate anticoagulation due to bleeding. This has led to the development and advancement of multiple surgical and percutaneous LAA closure devices to prevent embolic cerebrovascular accidents without the need for anticoagulation. In this article, we discuss the outcomes of major studies that utilized surgical LAA occlusion and its effectiveness. Furthermore, we summarize nonsurgical methods of LAA closure and future directions regarding LAA closure.

100 项与 Thrombin inhibitors(Virginia Commonwealth University) 相关的药物交易

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