ArticleThe Journal of biological chemistry2014
Inhibition of plasma kallikrein by a highly specific active site blocking antibody.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 2 of them syntheses that pooled it.
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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
81 citing papers in PubMed, 2 syntheses or guidelines pooled it, 119 citations in OpenAlex.
- Interventions for the long-term prevention of hereditary angioedema attacks.The Cochrane database of systematic reviews · 2022Pooled it
- Psychology and hereditary angioedema: A systematic review.Allergy and asthma proceedings · 2021Pooled it
- Intravenous lanadelumab for the treatment of moderately ill COVID-19 patients.British journal of clinical pharmacology · 2026Trial
- Sustained Effectiveness, Tolerability, and Safety of Long-Term Prophylaxis with Lanadelumab in Hereditary Angioedema: The Prospective, Phase 4, Noninterventional EMPOWER Real-World Study.Advances in therapy · 2025Trial
- Effective long-term prophylaxis with lanadelumab in adolescents with hereditary angioedema: EMPOWER/ENABLE.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2025Trial
- Lanadelumab for prevention of attacks of non-histaminergic normal C1 inhibitor angioedema: results from the randomized, double-blind CASPIAN Study and CASPIAN open-label extension.Frontiers in immunology · 2025Trial
- Long-term prevention of hereditary angioedema attacks with lanadelumab: The HELP OLE Study.Allergy · 2022Trial
- Impact of lanadelumab on health-related quality of life in patients with hereditary angioedema in the HELP study.Allergy · 2021Trial
- Lanadelumab demonstrates rapid and sustained prevention of hereditary angioedema attacks.Allergy · 2020Trial
- Bradykinin 1 Receptor Antagonist BI1026706 Does Not Reduce Central Retinal Thickness in Center-Involved Diabetic Macular Edema.Translational vision science & technology · 2020Trial
- Trial
- Lanadelumab Use for Hereditary Angioedema Long-Term Prophylaxis Over the Last 7 Years: A Narrative Review of Clinical and Real-World Data.Clinical reviews in allergy & immunology · 2026Review
- Achieving protease substrate-specific inhibition by mAb dual functional selections.Protein science : a publication of the Protein Society · 2026Article
- Hereditary angioedema attack trends among patients maintained on lanadelumab long-term prophylaxis.The journal of allergy and clinical immunology. Global · 2026Article
- Phage Display Technology: Design, Library Construction, and Panning Strategies for Antibody Development.Biomolecules & therapeutics · 2026Review
- Long-term effectiveness and safety of lanadelumab in Canadian patients with hereditary angioedema: a subanalysis of the EMPOWER study.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2026Article
- Donidalorsen for the Treatment of Hereditary Angioedema: A Review of Clinical Studies.Drug design, development and therapy · 2026Review
- Efficacy and acceptability of lanadelumab for long-term prophylaxis in hereditary angioedema: A Chinese multicenter real-world analysis.The World Allergy Organization journal · 2026Article
- Pharmacophore-driven antibody discovery on the yeast surface.bioRxiv : the preprint server for biology · 2025Article
- A single-centre retrospective study on the clinical characteristics of patients with hereditary angioedema and the therapeutic effect of lanadelumab.Orphanet journal of rare diseases · 2025Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Plasma kallikrein (pKal) proteolytically cleaves high molecular weight kininogen to generate the potent vasodilator and the pro-inflammatory peptide, bradykinin. pKal activity is tightly regulated in healthy individuals by the serpin C1-inhibitor, but individuals with hereditary angioedema (HAE) are deficient in C1-inhibitor and consequently exhibit excessive bradykinin generation that in turn causes debilitating and potentially fatal swelling attacks. To develop a potential therapeutic agent for HAE and other pKal-mediated disorders, we used phage display to discover a fully human IgG1 monoclonal antibody (DX-2930) against pKal. In vitro experiments demonstrated that DX-2930 potently inhibits active pKal (Ki = 0.120 ± 0.005 nM) but does not target either the zymogen (prekallikrein) or any other serine protease tested. These findings are supported by a 2.1-Å resolution crystal structure of pKal complexed to a DX-2930 Fab construct, which establishes that the pKal active site is fully occluded by the antibody. DX-2930 injected subcutaneously into cynomolgus monkeys exhibited a long half-life (t½ ∼ 12.5 days) and blocked high molecular weight kininogen proteolysis in activated plasma in a dose- and time-dependent manner. Furthermore, subcutaneous DX-2930 reduced carrageenan-induced paw edema in rats. A potent and long acting inhibitor of pKal activity could be an effective treatment option for pKal-mediated diseases, such as HAE.
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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.