ArticleNature communications2020
Targeted inhibition of activated protein C by a non-active-site inhibitory antibody to treat hemophilia.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Protein C and S activities in COVID-19: A systematic review and meta-analysis.Journal of thrombosis and thrombolysis · 2024Pooled it
- Personalized Treatment of Hemophilia: Matching Therapies to Patient Needs in a Rapidly Evolving Landscape.Drugs · 2026Review
- Achieving protease substrate-specific inhibition by mAb dual functional selections.Protein science : a publication of the Protein Society · 2026Article
- Activated protein C promotes human lung cancer progression through the release of tumor extracellular vesicles and transfer of microRNA-200a.Cell death & disease · 2025Article
- High-fat diet increases circulating palmitic acid produced by gut Bacteroides thetaiotaomicron to promote thrombosis.Cell reports. Medicine · 2025Article
- [Analysis of two cases of hereditary protein C deficiency causing venous thrombosis].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2025Article
- Divergent modulation of activated protein C pleiotropic functions by antibodies that differ by a single amino acid.Blood advances · 2025Article
- Sepsis-Induced Endothelial Barrier Dysfunction: Mechanisms, Pathology, and Therapeutic Advances.Research (Washington, D.C.) · 2025Review
- Discovery of New Inhibitors of Human Activated Protein C to Treat Hemophilia.Letters in drug design & discovery · 2024Article
- Nanolevel Immunomodulators in Sepsis: Novel Roles, Current Perspectives, and Future Directions.International journal of nanomedicine · 2024Review
- Selective modulation of activated protein C activities by a nonactive site-targeting nanobody library.Blood advances · 2023Article
- Considerations for shared decision management in previously untreated patients with hemophilia A or B.Therapeutic advances in hematology · 2023Review
- Coagulation Factor XIIIa and Activated Protein C Activate Platelets via GPVI and PAR1.International journal of molecular sciences · 2022Article
- Review
- Blocking human protein C anticoagulant activity improves clotting defects of hemophilia mice expressing human protein C.Blood advances · 2022Article
- Article
- An engineered activated factor V for the prevention and treatment of acute traumatic coagulopathy and bleeding in mice.Blood advances · 2022Article
- Hemophilia a patients with inhibitors: Mechanistic insights and novel therapeutic implications.Frontiers in immunology · 2022Review
- Factor-mimetic and rebalancing therapies in hemophilia A and B: the end of factor concentrates?Hematology. American Society of Hematology. Education Program · 2021Review
- A reactive center loop-based prediction platform to enhance the design of therapeutic SERPINs.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
35 authors at 4 institutions in 3 countries.
Funding
Abstract
Activated protein C (APC) is a plasma serine protease with antithrombotic and cytoprotective functions. Based on the hypothesis that specific inhibition of APC's anticoagulant but not its cytoprotective activity can be beneficial for hemophilia therapy, 2 types of inhibitory monoclonal antibodies (mAbs) are tested: A type I active-site binding mAb and a type II mAb binding to an exosite on APC (required for anticoagulant activity) as shown by X-ray crystallography. Both mAbs increase thrombin generation and promote plasma clotting. Type I blocks all APC activities, whereas type II preserves APC's cytoprotective function. In normal monkeys, type I causes many adverse effects including animal death. In contrast, type II is well-tolerated in normal monkeys and shows both acute and prophylactic dose-dependent efficacy in hemophilic monkeys. Our data show that the type II mAb can specifically inhibit APC's anticoagulant function without compromising its cytoprotective function and offers superior therapeutic opportunities for hemophilia.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.