更新于：2024-04-01

PLG

纤溶酶原

更新于：2024-04-01

基本信息

别名

纤维蛋白溶酶原、Activation peptide、Angiostatin

+ [5]

简介

Plasmin dissolves the fibrin of blood clots and acts as a proteolytic factor in a variety of other processes including embryonic development, tissue remodeling, tumor invasion, and inflammation. In ovulation, weakens the walls of the Graafian follicle. It activates the urokinase-type plasminogen activator, collagenases and several complement zymogens, such as C1 and C5. Cleavage of fibronectin and laminin leads to cell detachment and apoptosis. Also cleaves fibrin, thrombospondin and von Willebrand factor. Its role in tissue remodeling and tumor invasion may be modulated by CSPG4. Binds to cells. Angiostatin is an angiogenesis inhibitor that blocks neovascularization and growth of experimental primary and metastatic tumors in vivo. (Microbial infection) ENO/enoloase from parasite P.falciparum (strain NF54) interacts with PLG present in the mosquito blood meal to promote the invasion of the mosquito midgut by the parasite ookinete (PubMed:21949403). The catalytic active form, plasmin, is essential for the invasion of the mosquito midgut (PubMed:21949403). (Microbial infection) Binds to OspC on the surface of B.burgdorferi cells, possibly conferring an extracellular protease activity on the bacteria that allows it to traverse host tissue.

关联

重组人TNK组织型纤溶酶原激活剂 (广州铭康生物)

靶点

PLG

作用机制

PLG刺激剂

在研机构

石药集团明复乐药业（广州）有限公司

原研机构

石药集团明复乐药业（广州）有限公司

在研适应症

急性缺血性卒中 [+1]

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

中国

首次获批日期2015-01-14

Urokinase biosimilar(Sedico BV)

尿激酶生物类似药(Sedico BV)

靶点

PLG

作用机制

PLG刺激剂

在研机构

Sedico BV

原研机构

Sedico BV

在研适应症

心肌梗塞 [+2]

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

埃及

首次获批日期2014-01-01

Tissue plasminogen activator biosimilar (express in E coli)(RAS Lifesciences Pvt Ltd.)

组织纤溶酶原激活物（tPA）生物类似药(RAS Lifesciences Pvt Ltd.)

靶点

PLG

作用机制

PLG刺激剂

在研机构

RAS Lifesciences Pvt Ltd.

原研机构

RAS Lifesciences Pvt Ltd.

在研适应症

血栓形成

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

印度

首次获批日期2012-10-01

1,776

项与 PLG 相关的临床试验

NCT04387305 / Not yet recruiting临床3期IIT

Traumatic Injury Clinical Trial Evaluating Tranexamic Acid in Children (TIC-TOC): An Efficacy Study

Trauma is the leading cause of death and disability in children in the United States. The objective of this study is to evaluate the benefits and harms of tranexamic acid (TXA; a drug that stops bleeding) in severely injured children with hemorrhagic brain and/or torso injuries. Using thromboelastography, we will measure baseline fibrinolysis to assess for treatment effects of TXA at different levels of fibrinolysis.

开始日期2024-10-01

申办/合作机构

University of California, Davis

NCT06070350 / Not yet recruiting临床3期IIT

Massive Transfusion in Children: a Platform RCT of Whole Blood Compared to Component Therapy and Tranexamic Acid to Placebo in Life-threatening Traumatic Bleeding

The MATIC-2 is a multicenter clinical trial enrolling children who are less than 18 years of age with hemorrhagic shock potentially needing significant blood transfusion.
The primary objective of the clinical trial is to determine the effectiveness of Low Titer Group O Whole Blood (LTOWB) compared to component therapy (CT), and Tranexamic Acid (TXA) compared to placebo in decreasing 24-hour all-cause mortality in children with traumatic life threatening hemorrhage.

开始日期2024-09-01

申办/合作机构

University of Pittsburgh

[+1]

NCT06337838 / Not yet recruiting临床3期IIT

Bleeding Reduction in Acute and Chronic KidnEy patienTs Having Surgery (BRACKETS) Pilot Trial

The BRACKETS pilot study is a multicentre, prospective, randomized controlled trial of prophylactic preoperative tranexamic acid (TXA) versus placebo and, using a partial factorial design, of prophylactic preoperative desmopressin versus placebo.

开始日期2024-06-01

申办/合作机构

Population Health Research Institute

100 项与 PLG 相关的临床结果

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100 项与 PLG 相关的转化医学

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0 项与 PLG 相关的专利（医药）

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16,717

项与 PLG 相关的文献（医药）

2024-03-01·Protein science : a publication of the Protein Society

Degradation versus fibrillogenesis, two alternative pathways modulated by seeds and glycosaminoglycans.

Article

作者: Guglielmo Verona ; Sara Raimondi ; Diana Canetti ; P Patrizia Mangione ; Loredana Marchese ; Alessandra Corazza ; Francesca Lavatelli ; Julian D Gillmore ; Graham W Taylor ; Vittorio Bellotti ; Sofia Giorgetti

The mechanism that converts native human transthyretin into amyloid fibrils in vivo is still a debated and controversial issue. Commonly, non-physiological conditions of pH, temperature, or organic solvents are used in in vitro models of fibrillogenesis of globular proteins. Transthyretin amyloid formation can be achieved under physiological conditions through a mechano-enzymatic mechanism involving specific serine proteases such as trypsin or plasmin. Here, we investigate S52P and L111M transthyretin variants, both causing a severe form of systemic amyloidosis mostly targeting the heart at a relatively young age with heterogeneous phenotype among patients. Our studies on thermodynamics show that both proteins are significantly less stable than other amyloidogenic variants. However, despite a similar thermodynamic stability, L111M variant seems to have enhanced susceptibility to cleavage and a lower tendency to form fibrils than S52P in the presence of specific proteases and biomechanical forces. Heparin strongly enhances the fibrillogenic capacity of L111M transthyretin, but has no effect on the S52P variant. Fibrillar seeds similarly affect the fibrillogenesis of both proteins, with a stronger effect on the L111M variant. According to our model of mechano-enzymatic fibrillogenesis, both full-length and truncated monomers, released after the first cleavage, can enter into fibrillogenesis or degradation pathways. Our findings show that the kinetics of the two processes can be affected by several factors, such as intrinsic amyloidogenicity due to the specific mutations, environmental factors including heparin and fibrillar seeds that significantly accelerate the fibrillogenic pathway.

2024-02-23·PLoS pathogens

A tick saliva serpin, IxsS17 inhibits host innate immune system proteases and enhances host colonization by Lyme disease agent.

Article

作者: Thu-Thuy Nguyen ; Tae Heung Kim ; Emily Bencosme-Cuevas ; Jacquie Berry ; Alex Samuel Kiarie Gaithuma ; Moiz Ashraf Ansari ; Tae Kwon Kim ; Lucas Tirloni ; Zeljko Radulovic ; James J Moresco ; John R Yates ; Albert Mulenga

Lyme disease (LD) caused by Borrelia burgdorferi is among the most important human vector borne diseases for which there is no effective prevention method. Identification of tick saliva transmission factors of the LD agent is needed before the highly advocated tick antigen-based vaccine could be developed. We previously reported the highly conserved Ixodes scapularis (Ixs) tick saliva serpin (S) 17 (IxsS17) was highly secreted by B. burgdorferi infected nymphs. Here, we show that IxsS17 promote tick feeding and enhances B. burgdorferi colonization of the host. We show that IxsS17 is not part of a redundant system, and its functional domain reactive center loop (RCL) is 100% conserved in all tick species. Yeast expressed recombinant (r) IxsS17 inhibits effector proteases of inflammation, blood clotting, and complement innate immune systems. Interestingly, differential precipitation analysis revealed novel functional insights that IxsS17 interacts with both effector proteases and regulatory protease inhibitors. For instance, rIxsS17 interacted with blood clotting proteases, fXII, fX, fXII, plasmin, and plasma kallikrein alongside blood clotting regulatory serpins (antithrombin III and heparin cofactor II). Similarly, rIxsS17 interacted with both complement system serine proteases, C1s, C2, and factor I and the regulatory serpin, plasma protease C1 inhibitor. Consistently, we validated that rIxsS17 dose dependently blocked deposition of the complement membrane attack complex via the lectin complement pathway and protected complement sensitive B. burgdorferi from complement-mediated killing. Likewise, co-inoculating C3H/HeN mice with rIxsS17 and B. burgdorferi significantly enhanced colonization of mouse heart and skin organs in a reverse dose dependent manner. Taken together, our data suggests an important role for IxsS17 in tick feeding and B. burgdorferi colonization of the host.

2024-02-22·Journal of cellular and molecular medicine

Plasminogen activator inhibitor-1 serum levels in frontotemporal lobar degeneration.

Article

作者: Francesco Angelucci ; Katerina Veverova ; Alžbeta Katonová ; Martin Vyhnalek ; Jakub Hort

Plasminogen activator inhibitor-1 (PAI-1) impedes brain plasmin synthesis. Reduced plasmin activity facilitates cumulation of amyloid beta (Aβ) in Alzheimer's disease (AD). Since plasmin also regulates the synaptic activity, it is possible that altered PAI-1 is present in other neurodegenerative disorders. We investigated whether PAI-1 and its counter-regulatory tissue plasminogen activator (tPA) are altered in serum of patients with dementia due to frontotemporal lobar degeneration (FTLD). Thirty five FTLD patients (21 in mild cognitive impairment stage (MCI) and 14 in dementia stage) and 10 cognitively healthy controls were recruited. Serum tPA and PAI-1 protein levels were measured by anova. Correlation between biochemical and demographic data were explored by measuring Pearson correlation coefficient. Serum PAI-1 levels were elevated in the FTLD dementia group as compared to FTLD MCI and controls. tPA serum levels and PAI-1/tPA ratio did not significantly differ among groups. There was a negative correlation between PAI-1 serum levels and disease severity measured by MMSE score. No correlations of tPA serum levels and PAI-1/tPA ratio with MMSE were found. Increased PAI-1 serum levels may serve as a marker of dementia in FTLD, suggesting that, besides Aβ pathway, the plasmin system may affect cognition through synaptic activity.

项与 PLG 相关的新闻（医药）

2024-02-28

·生物探索

Sci Transl Med | 革命性疗法：利用siRNA靶向减少血浆纤溶酶原，为血友病患者带来希望

引言血友病A，作为一种遗传性出血障碍，长期以来对患者及其家庭构成了巨大挑战。这种疾病由于凝血因子VIII的缺乏或功能异常而导致血液凝固能力受损，从而使患者面临不断的出血风险，尤其是在关节和肌肉内部。这种持续的出血不仅会带来剧烈的疼痛，还可能导致严重的长期并发症，如关节损伤和出血性卒中，极大地影响患者的生活质量。尽管传统治疗方法，如凝血因子VIII替代疗法，已经能够在一定程度上帮助控制病情，但这些方法往往需要频繁的注射，并伴随着高昂的治疗成本和潜在的抗体产生风险。此外，对于那些因为抗体产生而无法接受常规凝血因子治疗的患者，治疗选择更加有限。因此，开发一种既有效又便捷的新型治疗方法，对于改善血友病A患者的治疗现状具有重要意义。近年来，随着分子生物学的飞速进展，小干扰RNA（siRNA）技术作为一种革命性的基因沉默工具，为多种遗传性和获得性疾病的治疗开辟了新的路径。siRNA疗法通过特异性地靶向并降解疾病相关基因的mRNA，从而抑制异常蛋白的产生，为精准医疗提供了新的策略。在血友病A的治疗领域，siRNA疗法展现出了其革命性的潜力。通过设计特异性的siRNA分子靶向影响血液凝固的关键基因，不仅可以在分子层面上调节凝血机制，还能避免传统治疗中的抗体产生问题和频繁注射的不便。更重要的是，siRNA疗法的高度特异性和可调节性为个体化治疗提供了可能，有望实现更精准、更有效的血友病A治疗方案。siRNA治疗原理siRNA（小干扰RNA）技术作为一种创新的基因沉默方法，在调控基因表达中扮演着至关重要的角色。通过设计特定序列的siRNA分子，可以精准地靶向并降解特定的mRNA分子，从而抑制相应蛋白的表达。这一机制为治疗多种疾病，包括遗传性疾病如血友病A，提供了新的治疗途径。在血友病A的治疗中，研究人员关注于纤溶酶原(plasminogen)的调控，因为这一因子在血液凝固过程中扮演重要角色。通过使用针对纤溶酶原的siRNA进行治疗，可以有效地减少血液中异常凝固因子的活性，从而控制血友病患者的出血倾向，这种方法的精准性和针对性为血友病的长期管理提供了新的策略。Versiti血液研究所进行的研究展示了siRNA治疗在血友病A长期控制中的潜力。该研究采用了一种特定的实验模型，模拟血友病A患者的生理状态，以评估siRNA治疗策略的有效性。研究人员设计了针对纤溶酶原的siRNA分子，并将其应用于血友病A模型中，观察其对出血控制的影响。研究结果表明，经过siRNA治疗的模型显示出显著的出血频率降低和出血量减少。这些发现证实了siRNA治疗策略在抑制异常凝固因子活性、控制出血倾向方面的长期有效性。此外，siRNA治疗的副作用较少，显示了其作为血友病A长期管理方案的潜力和安全性。从动物模型到临床试验的转化可能性在动物模型中，siRNA治疗已经显示出了显著的疗效，特别是在减少出血事件和改善血液凝固功能方面。这些前期研究的成功，为siRNA治疗从实验室到临床试验的转化奠定了坚实的基础。转化医学的核心在于将实验室研究成果应用于人类疾病的治疗。siRNA治疗血友病A的研究，正处于这一转化过程的关键时期。从动物模型到人类的转化不仅要求严格的安全性评估，还需要考虑到siRNA的递送系统、人体内的稳定性以及针对人类基因组的特异性调控。目前，多项研究正在探索不同的递送系统，以确保siRNA能够有效且安全地到达目标细胞。随着递送技术的不断进步和对siRNA分子设计的深入理解，将siRNA治疗从动物模型成功转化到临床试验的可能性正在逐渐增加。面临的挑战与未来研究方向尽管siRNA治疗的前景令人充满希望，但在临床应用前仍面临诸多挑战。首先，确保siRNA分子的稳定性和递送效率是一大挑战，因为RNA分子在体内容易被降解。此外，针对特定基因的高效且特异性沉默，同时避免非特异性基因表达的影响，也是实现临床应用的关键。未来研究需要着重解决这些挑战，特别是在改善递送系统和提高治疗特异性方面。此外，长期安全性研究将是未来工作的重点，以确保siRNA治疗不会引起不良的免疫反应或其他长期副作用。随着对siRNA治疗机制的深入理解和技术的不断进步，未来研究将更加注重个体化治疗方案的开发。这包括根据患者的基因背景和疾病特征，设计定制化的siRNA分子，以提高治疗效果和安全性。siRNA疗法的安全性与效果长期安全性评估siRNA治疗的副作用与安全性监测siRNA疗法作为一种新兴的基因沉默技术，其长期安全性仍然是研究的重点。尽管siRNA具有针对性强、副作用小的特点，但长期应用可能会引发一系列安全性问题。这包括潜在的免疫反应、非特异性基因沉默、以及可能对正常细胞功能产生的影响。因此，建立全面的安全性监测机制，对于评估siRNA治疗的长期副作用至关重要。长期应用siRNA疗法的潜在影响长期使用siRNA疗法可能会对患者的生物体系产生复杂的影响。研究指出，虽然短期内siRNA疗法显示出良好的安全性和耐受性，但其长期应用可能影响特定基因的表达，进而影响到整个基因调控网络。因此，深入研究siRNA疗法的长期应用对人体健康的潜在影响，对于确保其作为血友病A治疗手段的安全性至关重要。与传统疗法的比较siRNA疗法与现有治疗方法（如tranexamic acid）的效果对比传统的血友病A治疗方法，如tranexamic acid，主要通过抑制纤溶作用来减少出血。而siRNA疗法通过精确地靶向和沉默特定基因的表达，提供了一种潜在更为有效的治疗方案。比较两种疗法，siRNA疗法在降低出血事件、提高生活质量等方面显示出独特的优势，尽管这需要通过临床试验进一步验证。siRNA疗法的优势与潜在局限性siRNA疗法在治疗血友病A方面展现出显著的潜力，其优势包括高度的靶向性、可定制化治疗方案以及较低的副作用风险。然而，siRNA疗法的应用也面临一些局限性，如传递效率、稳定性以及潜在的免疫应答问题。因此，尽管siRNA疗法相较于传统疗法具有一定的优势，但其在临床应用中还需克服这些挑战。向临床试验迈进随着siRNA技术在血友病A治疗研究中取得显著进展，该领域的科研人员正致力于将这一创新疗法从实验室推向临床应用。目前，针对血友病A的siRNA疗法已经完成了一系列前期研究和动物实验，展现出了良好的治疗潜力和安全性。基于这些积极的结果，研究团队计划在2026年启动首批临床试验，标志着这一新兴疗法向临床应用迈出了重要一步。2026年临床试验的计划目前，siRNA疗法在动物模型中的应用已经证明了其在减少出血事件方面的有效性。通过精确靶向与血友病A相关的基因，这种疗法能够显著降低出血风险，同时减少对患者造成的副作用。基于这些前期成功，研究团队正在积极筹备2026年的临床试验，该试验将评估siRNA疗法在人体中的安全性和有效性。这一步骤对于siRNA疗法最终能否成为血友病A患者的可行治疗方案至关重要。除了血友病A之外，siRNA疗法的潜力还远未被完全挖掘。研究团队正与全球范围内的血液病专家合作，探讨这一疗法在其他类型出血性疾病中的应用可能性。通过跨学科合作，科研人员希望能够扩大siRNA疗法的应用范围，为更多患者提供有效的治疗选项。长期目标与患者影响siRNA疗法在血友病A治疗领域的应用不仅仅是科研成果的转化，更是对患者生活质量的深刻影响。通过提供一种更安全、更有效的治疗方法，siRNA疗法有望彻底改变血友病A患者的生活。对于血友病A患者而言，常规治疗方法往往伴随着重复的输血和长期的药物治疗，这不仅影响患者的日常生活，还可能带来一系列副作用。siRNA疗法的出现，以其靶向性强、副作用小的特点，为患者提供了一种新的治疗选择。通过减少治疗所需的医院访问次数和提高生活质量，siRNA疗法有望使血友病A患者能够享受到更加自由和健康的生活。随着siRNA疗法研究的深入和临床应用的逐步推进，其在血友病治疗领域的影响正日益凸显。这一创新疗法不仅为血友病A患者提供了新的希望，也为整个血友病治疗领域带来了新的治疗理念和方法。未来，随着更多的研究成果转化为临床应用，siRNA疗法有望成为改变血友病治疗现状、提高患者生活质量的重要力量。Q&A siRNA治疗血友病A的原理是什么？siRNA（小干扰RNA）是一种能够精确靶向并沉默特定基因表达的分子技术。在血友病A的治疗中，siRNA通过设计特异性序列，针对血液凝固过程中的关键蛋白，如凝血因子VIII（FVIII）的基因表达进行干预。通过降低或抑制异常基因的表达，siRNA有助于纠正血液凝固机制的失衡，从而减少出血事件。siRNA疗法与传统治疗相比有哪些优势？siRNA疗法相比传统治疗方法，如替代疗法和抗凝治疗，具有多项明显优势。首先，它提供了一种针对性更强的治疗策略，能够直接作用于疾病的分子机制，减少非特异性作用带来的副作用。其次，siRNA治疗具有较长的作用周期，能够实现持久的疗效，减少患者的治疗频率。此外，siRNA疗法的开发为那些对传统治疗方法有抵抗性或副作用的患者提供了新的治疗选择。siRNA治疗的潜在副作用有哪些？尽管siRNA治疗在血友病A的治疗中展现出巨大潜力，但其潜在副作用也不容忽视。最常见的副作用包括注射部位的反应、疲劳和头痛。在某些情况下，可能会出现免疫反应，尤其是当身体对siRNA分子产生免疫应答时。此外，精确靶向特定基因的能力虽然是siRNA疗法的优势，但也存在误靶或非特异性沉默其他重要基因的风险，可能会引起意料之外的生物学效应。如何参与siRNA治疗的临床试验？参与siRNA治疗的临床试验通常需要通过专业的医疗机构或研究中心。患者或其监护人首先应与治疗血友病A的医疗专家咨询，了解是否符合临床试验的入选标准。此外，可以访问临床试验注册网站，如ClinicalTrials.gov，搜索与血友病A相关的siRNA治疗临床试验，获取详细的试验信息及联系方式。积极与研究团队沟通，了解试验的目的、过程、潜在风险及收益，是参与试验的重要步骤。siRNA疗法对未来血友病治疗有何长远影响？siRNA疗法的发展为血友病A及其他遗传性疾病的治疗开辟了新的道路。随着研究的深入和技术的进步，siRNA治疗有望实现更高的精确度和更低的副作用，为患者提供更安全、更有效的治疗方案。长远来看，siRNA疗法不仅能够改善血友病A患者的生活质量，还可能彻底改变遗传性疾病的治疗模式，为未来的医疗治疗提供更广阔的可能性。参考文献Strilchuk AW, Hur WS, Batty P, et al. Lipid nanoparticles and siRNA targeting plasminogen provide lasting inhibition of fibrinolysis in mouse and dog models of hemophilia A. Sci Transl Med. 2024;16(735):eadh0027. doi:10.1126/scitranslmed.adh0027责编|探索君排版|探索君转载请注明来源于【生物探索】End往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文Nature | 破除传统：为何我们需要重新思考肿瘤的命名方式热文Nature | 2024年值得关注的七项技术热文Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文Nature | 癌症与神经系统的致命舞蹈

siRNA信使RNA

2024-02-27

·今日头条

最新！浙大医学院宋朋红/郑树森团队：揭示肝癌转移机制与治疗靶点

本文为转化医学网原创，转载请注明出处作者：Rainbow 导读：肝癌是一种发病率和死亡率较高的恶性肿瘤。 2月26日，浙江大学医学院宋朋红、郑树森共同通讯在期刊《CANCER COMMUNICATIONS》上在线发表题为“SERPINE2 promotes liver cancer metastasis by inhibiting c-Cbl-mediated EGFR ubiquitination and degradation”的研究论文，研究结果表明， SERPINE2通过c-Cbl介导的泛素化阻止EGFR降解，从而促进肝癌转移，这表明抑制SERPINE2-EGFR轴可能是肝癌治疗的潜在靶点。 https://onlinelibrary.wiley.com/doi/10.1002/cac2.12527 研究背景 01 肝癌仍然是全球面临的健康挑战，预计到2025年全球肝癌的年发病率将超过100万例。频繁的肝内和肝外转移是导致肝癌患者治疗效果和预后不佳的主要原因。 DNA甲基化是一种重要的表观遗传修饰，主要由DNA甲基转移酶包括DNA甲基转移酶1（DNMT1）、DNA甲基转移酶3A（DNMT3A）和DNA甲基转移酶3B（DNMT3B）介导，它在基因调控、结构维持和其他生物过程中起着重要作用，包括肝癌。 Serpin家族E成员2（SERPINE2），也称为PN-1，对于凝血酶、尿激酶和纤溶酶具有抗丝氨酸蛋白酶活性。先前的研究已经证明了SERPINE2在肿瘤转移中的潜在作用。然而，SERPINE2对肝癌进展的影响尚未得到证实。表皮生长因子受体（EGFR）是表面受体酪氨酸激酶家族的成员，促进肿瘤血管生成和转移。超过50%的肝癌患者表现出EGFR过表达。野生型EGFR可以激活多条信号转导通路，包括丝裂原活化蛋白激酶（MAPK）和JAK-信号转导子及转录激活子（STAT）信号通路。作为EGFR的经典E3泛素连接酶，c-Cbl介导EGFR的泛素化、内化和溶酶体降解。索拉非尼被广泛用作治疗晚期肝癌患者的多激酶抑制剂。先前的研究表明EGFR与索拉非尼治疗敏感性密切相关，但具体机制仍在研究中。研究发现 02 通过公共数据库筛选，已确定SERPINE2是一种受DNA甲基化调控的肿瘤促进因子。在肝癌组织中，SERPINE2表达显著增高，并与肝癌患者的不良预后相关。SERPINE2通过促进细胞伪足形成、细胞粘附、癌相关成纤维细胞激活、细胞外基质重塑和血管生成来促进肝癌转移。IP/MS实验证实，SERPINE2与EGFR相互作用，激活了表皮生长因子受体（EGFR）及其下游信号通路。在机制上，SERPINE2通过与E3泛素连接酶c-Cbl竞争抑制了EGFR的泛素化，并维持其蛋白稳定性。此外，在索拉非尼治疗后，肝癌细胞中EGFR被激活，而SERPINE2敲低诱导的EGFR下调显著增强了索拉非尼对肝癌的治疗效果。此外，研究人员发现，SERPINE2敲低对仑伐替尼治疗产生了增敏效应。研究结论 03 综上所述，研究结果表明， SERPINE2通过c-Cbl介导的泛素化阻止EGFR降解，从而促进肝癌转移，这表明抑制SERPINE2-EGFR轴可能是肝癌治疗的潜在靶点。参考资料： https://onlinelibrary.wiley.com/doi/10.1002/cac2.12527 注：本文旨在介绍医学研究进展，不能作为治疗方案参考。如需获得健康指导，请至正规医院就诊。热门·直播/活动 🕓 上海｜3月01日-02日 ▶第三届长三角单细胞组学技术应用论坛暨空间组学前沿论坛将在上海召开，诚邀您的参与！点击对应文字查看详情

临床结果蛋白降解靶向嵌合体临床1期

2024-02-20

·PipelineReview

Bayer initiates Phase II study with first-in-class anti-alpha2 antiplasmin antibody in patients with deep vein thrombosis

Anti-alpha2 antiplasmin antibody is being studied in patients with deep vein thrombosis to assess its potential as a thrombolytic Anti-alpha2 antiplasmin antibody might also provide potential treatment options in indications of high medical relevance BERLIN, Germany I February 20, 2024 I Bayer announced today the start of a Phase II clinical trial (SIRIUS study) with BAY3018250, an investigational first-in-class anti-alpha2 antiplasmin (anti-α2ap) antibody in patients with deep vein thrombosis (DVT). The results of this study might provide evidence of anti-α2ap antibody's potential as a treatment option in indications of high medical relevance. "We are excited to advance our anti-α2ap antibody to the next stage of clinical development in patients with deep vein thrombosis," said Christian Rommel, Member of the Executive Committee of Bayer AG's Pharmaceuticals Division and Head of Research and Development. "This study will also help to better understand if the anti-α2ap antibody is suitable as a thrombolytic to treat patient in indications of high medical relevance. By targeting alpha2 antiplasmin, we will have a more precise approach to modulate plasmin to break down thrombotic blood clots." Following the successful first-in-human trial, the goal of the randomized, double-blind, placebo-controlled, multi-center Phase II study (SIRIUS study) is to assess the efficacy and safety of BAY3018250 in patients with symptomatic proximal deep vein thrombosis. BAY3018250 is designed to target alpha2 antiplasmin. α2ap's primary function is to inhibit the enzymatic activity of plasmin and thereby balance the formation and dissolution of blood clots. About Bayer's Commitment in Cardiovascular Diseases Bayer is a leader in cardiology and is advancing a portfolio of innovative treatments in cardiovascular (CV) diseases of high unmet medical need. The strategy is to unlock the strong potential of the future CV market by transforming Bayer's portfolio into precision cardiology, addressing the high CV disease burden, and driving the long-term growth. Bayer's portfolio in the field of cardiovascular diseases already includes a number of innovative products and compounds in various stages of preclinical and clinical development. About Bayer Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. Its products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2022, the Group employed around 101,000 people and had sales of 50.7 billion euros. R&D expenses before special items amounted to 6.2 billion euros. For more information, go to www.bayer.com . Find more information at https://pharma.bayer.com Follow us on Facebook: http://www.facebook.com/bayer SOURCE: Bayer

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