更新于：2024-05-01

GP1BA

glycoprotein Ib platelet subunit alpha

更新于：2024-05-01

基本信息

别名

Antigen CD42b-alpha、CD42b、Glycocalicin

+ [9]

简介

GP-Ib, a surface membrane protein of platelets, participates in the formation of platelet plugs by binding to the A1 domain of vWF, which is already bound to the subendothelium.

关联

项与 GP1BA 相关的药物

Anfibatide

安菲博肽

靶点

GP1BA

作用机制

GP1BA抑制剂

在研机构

原研机构

在研适应症

非在研适应症

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

项与 GP1BA 相关的临床试验

NCT04404790 / Suspended临床1期

Phase I Clinical Trial of the Tolerance and Pharmacokinetics of Anfibatide in Health Volunteer

This is a phase 1, dose-escalation, and multidose study, aiming to investigate the tolerability, safety and pharmacokinetics of Anfibatate in healthy subjects. The study is divided into 2 intravenous single groups and 3 continuous administration groups. The dose of Anfibatate from 5 IU/60kg to 7 IU/60kg in intravenous single groups. The dose of Anfibatate from 0.002 IU/kg/h, 0.004 IU/kg/h to 0.008 IU/kg/h in continuous administration groups.

开始日期2020-09-01

申办/合作机构

李氏大药厂控股有限公司

NCT04021173 / Unknown status临床2期

A Multicenter, Randomized, Double-blind, Placebo-parallel, Phase II Clinical Trial of the Efficacy and Safety of Anfibatide in Treating Patients With Acquired Thrombotic Thrombocytopenic Purpura (TTP)

This is a multicenter, randomized, double-blind, parallel, placebo-controlled phase II clinical study. It is planned to recruit 74 patients with acquired thrombotic thrombocytopenic purpura (TTP). To evaluate the efficacy and safety of Anfibatide as an adjuvant therapy for plasma exchange in patients with acquired TTP.

开始日期2019-07-01

申办/合作机构

李氏大药厂控股有限公司

CTR20180962 / Recruiting临床1期

注射用抗血小板溶栓素Ⅰ期临床人体耐受性与药代动力学研究

1.考察健康受试者静脉推注本品单次用药和连续给药的安全性及耐受性；2.考察药效学特征指标，血小板聚集抑制率；3.初步考察心脏安全指标，为将来试验对患者心脏安全评估提供指导；4.探索5IU和7IU单次给药可以达到的血小板聚集抑制率及5IU和7IU连续给药可以维持的血小板聚集抑制率。

开始日期2019-01-28

申办/合作机构

兆科药业（合肥）有限公司

100 项与 GP1BA 相关的临床结果

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100 项与 GP1BA 相关的转化医学

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0 项与 GP1BA 相关的专利（医药）

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1,518

项与 GP1BA 相关的文献（医药）

2024-02-01·Journal of pediatric hematology/oncology

Clinical Analysis of Pediatric Acute Megakaryocytic Leukemia With CBFA2T3-GLIS2 Fusion Gene.

Article

作者: Yu Du ; Li Yang ; Shanshan Qi ; Zhi Chen ; Ming Sun ; Min Wu ; Bin Wu ; Fang Tao ; Hao Xiong

CBFA2T3-GLIS2 is the most frequent chimeric oncogene identified to date in non-Down syndrome acute megakaryocytic leukemia (AMKL), which is associated with extremely poor clinical outcome. The presence of this fusion gene is associated with resistance to high-intensity chemotherapy, including hematopoietic stem cell transplantation (HSCT), and a high cumulative incidence of relapse frequency. The clinical features and clinical effects of China Children's Leukemia Group-acute myeloid leukemia (AML) 2015/2019 regimens and haploidentical HSCT (haplo-HSCT) for treatment of 6 children harboring the CBFA2T3-GLIS2 fusion gene between January 2019 and December 2021 were retrospectively analyzed. The 6 patients included 4 boys and 2 girls with a median disease-onset age of 19.5 months (range: 6-67 mo) who were diagnosed with AMKL. Flow cytometry demonstrated CD41a, CD42b, and CD56 expression and lack of HLA-DR expression in all 6 patients. All the children were negative for common leukemia fusion genes by reverse transcription polymerase chain reaction, but positive for the CBFA2T3-GLIS2 fusion gene by next-generation sequencing and RNA sequencing. All patients received chemotherapy according to China Children's Leukemia Group-AML 2015/2019 regimens, and 4 achieved complete remission. Four children underwent haplo-HSCT with posttransplant cyclophosphamide-based conditioning; 3 had minimal residual disease negative (minimal residual disease <0.1%) confirmed by flow cytometry at the end of the follow-up, with the remaining patient experiencing relapse at 12 months after transplantation. Transcriptome RNA sequencing is required for the detection of the CBFA2T3-GLIS2 fusion gene and for proper risk-based allocation of pediatric patients with AML in future clinical strategies. Haplo-HSCT with posttransplant cyclophosphamide-based conditioning may improve survival in children with AMKL harboring the fusion gene.

2024-01-30·Endocrine, metabolic & immune disorders drug targets

Genetic Polymorphisms of GP1BA, PEAR1, and PAI-1 May Be Associated with Serum sIgE and Blood Eosinophil Levels in Chinese Patients with Allergic Diseases.

Article

作者: Rui Tang ; Xiaohong Lyu ; Jinlyu Sun ; Hong Li

BACKGROUND:

It has been suggested that genetic factors may be substantially linked to allergy disorders.

OBJECTIVE:

This study aims to investigate the relationship between the serum specific Immunoglobulin E [sIgE], blood eosinophil, and the polymorphisms of glycoprotein Ib alpha gene [GP1BA] rs6065, platelet endothelial aggregation receptor 1 gene [PEAR1] rs12041331, and plasminogen activator inhibitor 1 gene [PAI-1] rs1799762.

METHODS:

From the Peking Union Medical College Hospital, this study enrolled 60 healthy participants and 283 participants with allergic diseases. TaqMan-minor groove binder [MGB] quantitative polymerase chain reaction [qPCR] was used to examine the gene polymorphisms in each group.

RESULTS:

The TaqMan-MGB qPCR results were completely consistent with the DNA sequencing results, according to other studies in this medical center [Kappa =1, p <0.001]. The GP1BA rs6065, PEAR1 rs12041331, and PAI-1 rs1799762 polymorphisms did not show different distribution between allergy patients and healthy individuals. Concerning allergy patients, the CT [n=33] genotype of GP1BA rs6065 had higher blood eosinophil level than the CC [n=250] genotype [0.59, IQR 0.32-0.72 vs 0.31, IQR 0.15-0.61, *109/L, p =0.005]. The serum sIgE of AA [n=46] genotype of PEAR1 rs12041331 was lower [median 3.7, interquartile quartiles [IQR] 0.2-16.8, kU/L] than the GA [n=136] and GG [n=101] genotypes [GA median 16.3, IQR 3.1-46.3, kU/L, p = 0.002; GG median 12.9, IQR 3.0-46.9, kU/L, p =0.003]. The GA genotypes of PEAR1 rs12041331were with higher blood eosinophil levels [median 0.42, IQR 0.17-0.74 *109/L] than the AA genotype [median 0.25, IQR 0.15-0.41*109/L, p =0.012]. The sIgE of the 5G5G [n=44] genotype of PAI-1 rs1799762 was lower [median 5.0, IQR 0.1-22.8, kU/L] than the 4G5G [n=144] [median 17.3, IQR 3.7-46.0, kU/L, p = 0.012].

CONCLUSION:

The GP1BA rs6065, PEAR1 rs12041331, and PAI-1 rs1799762 polymorphisms may be associated with the genetic susceptibility of serum sIgE or blood eosinophil in Chinese allergic disease patients.

2024-01-09·Scientific reports

Establishment of a forward primers-superposed amplification analysis for accurate aspirin pharmacogenomic measurement.

Article

作者: Chun-Yan Li ; Ping Yang ; Jie Zheng ; Jing Zhang ; Yi-Qing Liu ; Xiao-Quan Liu ; Yue Hu ; Wen-Jun Lan

Genotyping of gDNA rs12041331 (PEAR1), rs6065 (GP1BA), and rs730012 (LTC4S) can provide systematic guidance on the use of aspirin. However, an accurate, reliable and economical approach to simultaneous detection of the above single nucleotide polymorphisms (SNPs) is not reported. Herein, we designed and substantiated an allele-specific (AS) forward primer-superposed amplification analysis for measurement of the SNPs in PEAR1, GP1BA and LTC4S genes, in which the values of ∆Cq (differences in threshold cycles between the wild-type forward primer-based assay and the mutated-type forward primer-based assay) were employed to decide genotype. Mismatch AS forward primers were screened with the singleplex amplification analysis. Moreover, Cq extension optimized by AS forward primer superposition was observed in the selected forward primer-based triplex analysis. Further, robustness assessment of the triplex analysis showed the amplification efficiency ranging from 0.9 to 1.1. Precision test demonstrated the coefficient of variation of less than 2%. And the detective results of 189 DNA samples was completely concordant with that of commercial Sanger sequencing. In summary, we developed a simple, accurate and economical approach to genotyping of rs12041331 (PEAR1), rs6065 (GP1BA) and rs730012 (LTC4S) to provide a valuable pharmacogenomics tool for guidance of aspirin delivery.

项与 GP1BA 相关的新闻（医药）

2024-01-21

·生物谷

《细胞》子刊：中山大学/苏州大学团队发现，抑制Erbin蛋白可提升B细胞抗癌能力！

我国学者最新研究——专门靶向敲除血小板/巨核细胞中的Erbin，就可以借助B细胞的抗癌免疫能力，来有效抑制肠癌肺转移。近日《细胞·代谢》刊登的一项我国学者最新研究，就揭示了从血小板/巨核细胞（MKs）入手、调动B细胞抗肿瘤免疫能力的全新方法：中山大学孙逸仙纪念医院李建明团队、苏州大学医学部沈彤团队共同发现，血小板/巨核细胞增多及其中高表达的Erbin蛋白，会通过调控代谢途径抑制B细胞抗癌能力，而干预Erbin-线粒体轴则可有效减少结直肠癌的肺转移[1]。上面这段总结里有三位“主角”，其中就有Erbin蛋白这个看上去很像蹭“尔滨”热点的名字，但这还真不是随便编的：Erbin的全称其实是“ErbB2相互作用蛋白”，既然能与ErbB2也就是HER2发生相互作用，那肯定也和癌症关系匪浅，而且不光是乳腺癌，此前就有研究揭示了Erbin在肠癌、肝癌中的影响[2-3]。本次中山大学/苏州大学团队的研究切入点，是三位主角中大家最熟悉的血小板，巨核细胞则是负责产生血小板的细胞；进入癌症免疫治疗时代，血小板和巨核细胞也常被视为一类特殊的免疫细胞，毕竟血小板也没少掺和抗肿瘤免疫。研究者们注意到，发生远处转移的肠癌患者，血小板计数往往高于未发生转移的患者，与其它血细胞趋势截然相反，该作何解释呢？研究者们在小鼠实验中重现了上述发现，即肠癌远处转移与血小板计数显著升高同时存在，对肠癌患者原发灶/转移灶样本的KEGG富集分析还提示，基因表达水平存在显著差异的既有血小板凝血功能相关通路，也有B细胞分化、脂质应答和骨髓成熟、血液循环通路。这就意味着B细胞也牵扯进来了，且血小板（CD42b+细胞）和B细胞在转移灶中相距也很近。而在对肠癌肺转移灶的基因通路富集分析中，研究者们还发现了ErbB2信号通路和Erbin蛋白的高表达，三位主角就此全部到齐了，那么它们之间到底是个什么关系呢？肠癌远处转移与血小板计数显著升高相关，提示血小板和B细胞的参与研究者们完全敲除了小鼠体内血小板/巨核细胞的Erbin表达，再建立肠癌肺转移模型，发现肺转移立刻被有效压制了，且骨髓、外周血和肺部的巨核细胞、血小板及免疫细胞组成也相应发生了显著改变，其中肺部的CD42b+血小板/巨核细胞数量增多了1.5倍，而且荷瘤小鼠体内的血小板/巨核细胞数量是无瘤小鼠的10倍，说明它们正是在肺转移灶形成后才聚集而来。敲除Erbin表达不仅改变了血小板数量，还使它们黏附癌细胞、形成物理保护屏障的能力减弱了；与此同时，小鼠肺部的B细胞（包括记忆B细胞和浆细胞）数量也显著增多，血小板黏附它们却更容易了，但血小板却又不会黏附CD8+T细胞，看来它们只和B细胞间有瓜葛。敲除Erbin表达对血小板及B细胞的影响进一步实验还显示，即使把敲除Erbin表达小鼠体内的血小板、巨核细胞乃至B细胞单独分离出来，作为过继性细胞疗法使用，也足以在CD8+T细胞已处于耗竭状态的小鼠模型体内，有效抑制肠癌肺转移，且这种疗效依赖于B细胞对CD8+T细胞免疫功能的恢复。那接下来，就得看看血小板/巨核细胞和Erbin是如何调控B细胞的了：分析显示，敲除Erbin可使血小板内的内皮细胞粘附分子（ESAM）水平显著下降，且Erbin与ESAM间有明确的相互作用，这可能解释了血小板黏附癌细胞能力的减弱；同时线粒体氧化磷酸化水平上升，使血小板/巨核细胞分泌更多酰基肉碱（Acar）等脂质代谢产物。而在肠癌原发灶、转移灶和外周血中，Acar又会通过表观遗传途径，即H3K27ac组蛋白修饰调控CD79a、IRF1等关键基因或生长因子，增强B细胞的线粒体电子传递链复合物活性和线粒体氧化磷酸化水平，并同时介导PD-1蛋白的泛素化降解，以显著增强B细胞的抗肿瘤免疫能力。 Erbin-线粒体轴对B细胞抗肿瘤免疫能力的调控因此，专门靶向敲除血小板/巨核细胞中的Erbin，就可以借助B细胞的抗癌免疫能力，来有效抑制肠癌肺转移，研究者们在论文中还表示，以血小板作为干预目标还是一种相当安全的策略，因为血小板的寿命短、代谢速度快，长期被针对可能也不会带来明显的副作用，很适合以预防癌症复发和转移为目标的疗法。

免疫疗法临床结果

2024-01-19

·奇点网

抗癌，就是得一起上！

*仅供医学专业人士阅读参考“抗击癌症，全员有责”，奇点糕真想把这句话送给体内所有的免疫细胞，大家都得行动起来才行，不能总让CD8+T细胞、NK细胞们冲上去迎敌，但要想把各类免疫细胞都调动起来参战，就得明确关键的调控通路才行。近日《细胞·代谢》刊登的一项我国学者最新研究，就揭示了从血小板/巨核细胞（MKs）入手、调动B细胞抗肿瘤免疫能力的全新方法：中山大学孙逸仙纪念医院李建明团队、苏州大学医学部沈彤团队共同发现，血小板/巨核细胞增多及其中高表达的Erbin蛋白，会通过调控代谢途径抑制B细胞抗癌能力，而干预Erbin-线粒体轴则可有效减少结直肠癌的肺转移[1]。论文核心内容总结上面这段总结里有三位“主角”，其中就有Erbin蛋白这个看上去很像蹭“尔滨”热点的名字，但这还真不是随便编的：Erbin的全称其实是“ErbB2相互作用蛋白”，既然能与ErbB2也就是HER2发生相互作用，那肯定也和癌症关系匪浅，而且不光是乳腺癌，此前就有研究揭示了Erbin在肠癌、肝癌中的影响[2-3]。本次中山大学/苏州大学团队的研究切入点，是三位主角中大家最熟悉的血小板，巨核细胞则是负责产生血小板的细胞；进入癌症免疫治疗时代，血小板和巨核细胞也常被视为一类特殊的免疫细胞，毕竟血小板也没少掺和抗肿瘤免疫。研究者们注意到，发生远处转移的肠癌患者，血小板计数往往高于未发生转移的患者，与其它血细胞趋势截然相反，该作何解释呢？研究者们在小鼠实验中重现了上述发现，即肠癌远处转移与血小板计数显著升高同时存在，对肠癌患者原发灶/转移灶样本的KEGG富集分析还提示，基因表达水平存在显著差异的既有血小板凝血功能相关通路，也有B细胞分化、脂质应答和骨髓成熟、血液循环通路。这就意味着B细胞也牵扯进来了，且血小板（CD42b+细胞）和B细胞在转移灶中相距也很近。而在对肠癌肺转移灶的基因通路富集分析中，研究者们还发现了ErbB2信号通路和Erbin蛋白的高表达，三位主角就此全部到齐了，那么它们之间到底是个啥关系呢？肠癌远处转移与血小板计数显著升高相关，提示血小板和B细胞的参与研究者们完全敲除了小鼠体内血小板/巨核细胞的Erbin表达，再建立肠癌肺转移模型，发现肺转移立刻被有效压制了，且骨髓、外周血和肺部的巨核细胞、血小板及免疫细胞组成也相应发生了显著改变，其中肺部的CD42b+血小板/巨核细胞数量增多了1.5倍，而且荷瘤小鼠体内的血小板/巨核细胞数量是无瘤小鼠的10倍，说明它们正是在肺转移灶形成后才聚集而来。敲除Erbin表达不仅改变了血小板数量，还使它们黏附癌细胞、形成物理保护屏障的能力减弱了；与此同时，小鼠肺部的B细胞（包括记忆B细胞和浆细胞）数量也显著增多，血小板黏附它们却更容易了，但血小板却又不会黏附CD8+T细胞，看来它们只和B细胞间有瓜葛。敲除Erbin表达对血小板及B细胞的影响进一步实验还显示，即使把敲除Erbin表达小鼠体内的血小板、巨核细胞乃至B细胞单独分离出来，作为过继性细胞疗法使用，也足以在CD8+T细胞已处于耗竭状态的小鼠模型体内，有效抑制肠癌肺转移，且这种疗效依赖于B细胞对CD8+T细胞免疫功能的恢复。那接下来，就得看看血小板/巨核细胞和Erbin是如何调控B细胞的了：分析显示，敲除Erbin可使血小板内的内皮细胞粘附分子（ESAM）水平显著下降，且Erbin与ESAM间有明确的相互作用，这可能解释了血小板黏附癌细胞能力的减弱；同时线粒体氧化磷酸化水平上升，使血小板/巨核细胞分泌更多酰基肉碱（Acar）等脂质代谢产物。而在肠癌原发灶、转移灶和外周血中，Acar又会通过表观遗传途径，即H3K27ac组蛋白修饰调控CD79a、IRF1等关键基因或生长因子，增强B细胞的线粒体电子传递链复合物活性和线粒体氧化磷酸化水平，并同时介导PD-1蛋白的泛素化降解，以显著增强B细胞的抗肿瘤免疫能力。Erbin-线粒体轴对B细胞抗肿瘤免疫能力的调控因此，专门靶向敲除血小板/巨核细胞中的Erbin，就可以借助B细胞的抗癌免疫能力，来有效抑制肠癌肺转移，研究者们在论文中还表示，以血小板作为干预目标还是一种相当安全的策略，因为血小板的寿命短、代谢速度快，长期被针对可能也不会带来明显的副作用，很适合以预防癌症复发和转移为目标的疗法。参考文献：[1]Zhang Z, Xu X, Zhang D, et al. Targeting Erbin-mitochondria axis in platelets/megakaryocytes promotes B cell-mediated antitumor immunity [J]. Cell Metabolism, 2024. [2]Stevens P D, Wen Y A, Xiong X, et al. Erbin suppresses KSR1-mediated RAS/RAF signaling and tumorigenesis in colorectal cancer[J]. Cancer Research, 2018, 78(17): 4839-4852.[3]Wu H, Yao S, Zhang S, et al. Elevated expression of Erbin destabilizes ERα protein and promotes tumorigenesis in hepatocellular carcinoma[J]. Journal of Hepatology, 2017, 66(6): 1193-1204.本文作者丨谭硕

免疫疗法

2022-12-13

·Science Daily

Blood clotting research holds hope for sepsis

Researchers who identified a novel mechanism for platelet activation in pathogenic blood clotting (thrombosis) are now turning their attention to sepsis. Researchers from the University of Birmingham, UK, who identified a novel mechanism for platelet activation in pathogenic blood clotting (thrombosis) are now turning their attention to sepsis. Identified by Associate Professor Julie Rayes and Dr Martina Colicchia from the Birmingham Platelet Group, and described in a recent paper in Blood, this previously unknown axis comprises platelet receptor glycoprotein I alpha (GPIb?), and an anti-microbial protein S100A8/A9, which is released from activated immune cells. The mechanism is not blocked by classical anti-platelet drugs currently used to treat arterial thrombosis, and is distinct from the well-described 'clotting cascade' that limits blood loss following injury. Dr Rayes explains: "When clots are formed at the site of a vascular injury, two main populations of platelet are seen. Highly activated and aggregated platelets are located at the core of the clot, while procoagulant platelets are present at the shell around the core and support the generation of fibrin which stabilizes the clot. "The S100A8/A9-GPIb? axis does not induce platelet aggregation but it does induce the formation of procoagulant platelets and accelerates fibrin activation and thrombosis. This axis might be more relevant in disease states where the activation of innate immune cells and platelets play a pivotal role in clotting." High levels of S100A8/A9 are seen in the blood in thrombo-inflammatory diseases including myocardial infarction (MI), deep vein thrombosis (DVT) and infections such as COVID-19 and sepsis, and their presence correlates with thrombotic complications, and worse outcomes for patients. The researchers believe this novel mechanism may be relevant in thrombosis observed under chronic inflammatory conditions and acute infections and believe that the interaction of S100A8/A9 with multiple receptors* makes it an interesting target to limit both clotting and inflammation during sepsis. Dr Rayes said: "Thrombosis is a major complication during infection, so drugs are needed that target pathogenic clotting while maintaining vascular integrity and normal clotting process (haemostasis). By selectively targeting S100A8/A9, we aim to target a key pathogenic inflammatory and thrombotic molecule to limit both inflammation and thrombosis during infection." Associate Professor Rayes presented at the 63rd American Society of Hematology (ASH) Annual Meeting on Monday December 12, 2022 (16.30-18.05 CST). She expects to publish the results of the sepsis study in 2023. University of Birmingham Enterprise has filed a patent application covering the targeting of the S100A8/A9-GPIb? axis in the treatment and prevention of thrombosis in chronic inflammatory and thrombotic diseases and is now seeking partners for commercial development or licensing.

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