Dimeric glycoprotein VIFc(Corimmun)(Dimeric glycoprotein VIFc(Corimmun)) - 药物靶点：GPVI_在研适应症：急性冠状动脉综合征，冠心病_专利_临床

概要

基本信息

药物类型

融合蛋白

别名

Dimeric glycoprotein VI-Fc、GPVI-Fc、Revacept

+ [1]

靶点

GPVI

作用机制

GPVI抑制剂(血小板膜糖蛋白VI抑制剂)

治疗领域

心血管疾病

在研适应症

急性冠状动脉综合征冠心病

非在研适应症

一过性黑朦动脉粥样硬化颈动脉狭窄+ [4]

原研机构

Corimmun GmbH

在研机构

Corimmun GmbH

非在研机构

advanceCOR GmbH

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

登录后查看时间轴

关联

4

项与 Dimeric glycoprotein VIFc(Corimmun) 相关的临床试验

NCT03312855 / Completed临床2期IIT

Revacept, a Novel Inhibitor of Platelet Adhesion in Patients With Stable Coronary Artery Disease Undergoing Elective Percutaneous Coronary Interventions: a Phase II, Multicentre, Randomised, Double-blind and Placebo-controlled Study

The main objective is to evaluate the efficacy and safety of treatment with 2 doses (80 and 160 mg) of Revacept versus placebo in patients with stable coronary artery disease undergoing PCI.

开始日期2017-11-20

申办/合作机构

Deutsches Herzzentrum Berlin

[+4]

EUCTR2015-000686-32-DE / Not yet recruiting临床2期

Revacept, a novel inhibitor of platelet adhesion in patients with stable coronary artery disease undergoing elective percutaneous coronary interventions: A phase II, multicentre, randomised, dose-finding, double-blind and placebo-controlled study.

开始日期2017-02-10

申办/合作机构-

NCT01645306 / Completed临床2期

Revacept, an Inhibitor of Platelet Adhesion in Symptomatic Carotid Stenosis: A Phase II, Multicentre; Randomised, Dose-finding, Double-blind and Placebo Controlled Superiority Study With Parallel Groups

Patients suffering from symptomatic carotid artery stenosis, transient ischemic attacks (TIAs), amaurosis fugax or stroke receive either Revacept (single dose) plus antiplatelet monotherapy or monotherapy alone.
Patients receive a single dose of trial medication by intravenous infusion for 20 minutes. Patients are followed up one and three days after treatment, at 3 months and by a telephone interview at 12 months.

开始日期2013-03-08

申办/合作机构

advanceCOR GmbH

100 项与 Dimeric glycoprotein VIFc(Corimmun) 相关的临床结果

登录后查看更多信息

100 项与 Dimeric glycoprotein VIFc(Corimmun) 相关的转化医学

登录后查看更多信息

100 项与 Dimeric glycoprotein VIFc(Corimmun) 相关的专利（医药）

登录后查看更多信息

34

项与 Dimeric glycoprotein VIFc(Corimmun) 相关的文献（医药）

2023-06-01·Journal of Nuclear Medicine

Radiolabeled GPVI-Fc for PET Imaging of Multiple Extracellular Matrix Fibers: A New Look into Pulmonary Fibrosis Progression

Article

作者: Pichler, Bernd J ; Maurer, Andreas ; Gawaz, Meinrad ; Quintanilla-Martinez, Leticia ; Schaller, Martin ; Beziere, Nicolas ; Gonzalez-Menendez, Irene ; Isser, Simon ; Reischl, Gerald

Invariably fatal and with a particularly fast progression, pulmonary fibrosis (PF) is currently devoid of curative treatment options. Routine clinical diagnosis relies on breathing tests and visualizing the changes in lung structure by CT, but anatomic information is often not sufficient to identify early signs of progressive PF. For more efficient diagnosis, additional imaging techniques were investigated in combination with CT, such as ¹⁸F-FDG PET, although with limited success because of lack of disease specificity. Therefore, novel molecular targets enabling specific diagnosis are investigated, in particular for molecular imaging techniques. Methods: In this study, we used a ⁶⁴Cu-radiolabeled platelet glycoprotein VI fusion protein (⁶⁴Cu-GPVI-Fc) targeting extracellular matrix (ECM) fibers as a PET tracer to observe longitudinal ECM remodeling in a bleomycin-induced PF mouse model. Results: ⁶⁴Cu-GPVI-Fc showed significant uptake in fibrotic lungs, matching histology results. Contrary to ¹⁸F-FDG PET measurements, ⁶⁴Cu-GPVI-Fc uptake was linked entirely to the fibrotic activity of tissue and not was susceptible to inflammation. Conclusion: Our study highlights ⁶⁴Cu-GPVI-Fc as a specific tracer for ECM remodeling in PF, with clear therapy-monitoring and clinical translation potential.

2023-06-01·Thrombosis and Haemostasis

Pharmacological Inhibition of Glycoprotein VI- and Integrin α2β1-Induced Thrombus Formation Modulated by the Collagen Type

Article

作者: Heemskerk, Johan W. M. ; Farndale, Richard W. ; Watson, Steve P. ; Henskens, Yvonne M.C. ; Gawaz, Meinrad P. ; Jooss, Natalie J. ; Jandrot-Perrus, Martine ; Poulter, Natalie S.

Background In secondary cardiovascular disease prevention, treatments blocking platelet-derived secondary mediators pose a risk of bleeding. Pharmacological interference of the interaction of platelets with exposed vascular collagens is an attractive alternative, with clinical trials ongoing. Antagonists of the collagen receptors, glycoprotein VI (GPVI), and integrin α2β1, include recombinant GPVI-Fc dimer construct Revacept, 9O12 mAb based on the GPVI-blocking reagent Glenzocimab, Syk tyrosine-kinase inhibitor PRT-060318, and anti-α2β1 mAb 6F1. No direct comparison has been made of the antithrombic potential of these drugs. Methods Using a multiparameter whole-blood microfluidic assay, we compared the effects of Revacept, 9O12-Fab, PRT-060318, or 6F1 mAb intervention with vascular collagens and collagen-related substrates with varying dependencies on GPVI and α2β1. To inform on Revacept binding to collagen, we used fluorescent-labelled anti-GPVI nanobody-28. Results and Conclusion In this first comparison of four inhibitors of platelet–collagen interactions with antithrombotic potential, we find that at arterial shear rate: (1) the thrombus-inhibiting effect of Revacept was restricted to highly GPVI-activating surfaces; (2) 9O12-Fab consistently but partly inhibited thrombus size on all surfaces; (3) effects of GPVI-directed interventions were surpassed by Syk inhibition; and (4) α2β1-directed intervention with 6F1 mAb was strongest for collagens where Revacept and 9O12-Fab were limitedly effective. Our data hence reveal a distinct pharmacological profile for GPVI-binding competition (Revacept), GPVI receptor blockage (9O12-Fab), GPVI signaling (PRT-060318), and α2β1 blockage (6F1 mAb) in flow-dependent thrombus formation, depending on the platelet-activating potential of the collagen substrate. This work thus points to additive antithrombotic action mechanisms of the investigated drugs.

2023-02-01·Biophysical Journal

Investigating thrombin-loaded fibrin in whole blood clot microfluidic assay via fluorogenic peptide

Article

作者: Crossen, Jennifer ; Diamond, Scott L ; Shankar, Kaushik N

During clotting under flow, thrombin rapidly generates fibrin, whereas fibrin potently sequesters thrombin. This co-regulation was studied using microfluidic whole blood clotting on collagen/tissue factor, followed by buffer wash, and a start/stop cycling flow assay using the thrombin fluorogenic substrate, Boc-Val-Pro-Arg-AMC. After 3 min of clotting (100 s^-1) and 5 min of buffer wash, non-elutable thrombin activity was easily detected during cycles of flow cessation. Non-elutable thrombin was similarly detected in plasma clots or arterial whole blood clots (1000 s^-1). This thrombin activity was ablated by Phe-Pro-Arg-chloromethylketone (PPACK), apixaban, or Gly-Pro-Arg-Pro to inhibit fibrin. Reaction-diffusion simulations predicted 108 nM thrombin within the clot. Heparin addition to the start/stop assay had little effect on fibrin-bound thrombin, whereas addition of heparin-antithrombin (AT) required over 6 min to inhibit the thrombin, indicating a substantial diffusion limitation. In contrast, heparin-AT rapidly inhibited thrombin within microfluidic plasma clots, indicating marked differences in fibrin structure and functionality between plasma clots and whole blood clots. Addition of GPVI-Fab to blood before venous or arterial clotting (200 or 1000 s^-1) markedly reduced fibrin-bound thrombin, whereas GPVI-Fab addition after 90 s of clotting had no effect. Perfusion of AF647-fibrinogen over washed fluorescein isothiocyanate (FITC)-fibrin clots resulted in an intense red layer around, but not within, the original FITC-fibrin. Similarly, introduction of plasma/AF647-fibrinogen generated substantial red fibrin masses that did not penetrate the original green clots, demonstrating that fibrin cannot be re-clotted with fibrinogen. Overall, thrombin within fibrin is non-elutable, easily accessed by peptides, slowly accessed by average-sized proteins (heparin/AT), and not accessible to fresh fibrinogen.

100 项与 Dimeric glycoprotein VIFc(Corimmun) 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

登录

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
动脉粥样硬化	临床2期	英国	advanceCOR GmbH	2013-03-08
动脉粥样硬化	临床2期	德国	advanceCOR GmbH	2013-03-08
颈动脉狭窄	临床2期	英国	advanceCOR GmbH	2013-03-08
颈动脉狭窄	临床2期	德国	advanceCOR GmbH	2013-03-08
短暂性脑缺血发作	临床2期	英国	advanceCOR GmbH	2013-03-08
短暂性脑缺血发作	临床2期	德国	advanceCOR GmbH	2013-03-08
脑卒中	临床2期	英国	advanceCOR GmbH	2013-03-08
脑卒中	临床2期	德国	advanceCOR GmbH	2013-03-08
急性冠状动脉综合征	临床2期	-	Corimmun GmbH	-
冠心病	临床2期	-	Corimmun GmbH	-

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01645306 (Pubmed)	临床2期	颈动脉狭窄	160	Placebo	選構積鏇遞蓋鑰選醖夢(遞鬱顧艱築鏇壓製簾憲) = 鑰窪觸膚鑰蓋構願鏇簾齋鏇醖蓋壓鑰衊網廠簾 (艱齋齋壓顧網廠衊艱醖, 0.88 ~ 1.53)	积极	2022-06-13
				Revacept 40 mg	選構積鏇遞蓋鑰選醖夢(遞鬱顧艱築鏇壓製簾憲) = 顧顧構鏇獵艱鹹製壓簾齋鏇醖蓋壓鑰衊網廠簾 (艱齋齋壓顧網廠衊艱醖, 0.78 ~ 1.42)