ArticleThe Biochemical journal2012
Generation and characterization of non-competitive furin-inhibiting nanobodies.
Article in The Biochemical journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- Single Nucleotide Polymorphism (rs4932178) in the P1 Promoter of FURIN Is Not Prognostic to Colon Cancer.BioMed research international · 2015Trial
- The expanding role of protease therapeutics (2012-2026): from replacement therapies to immune system modulation and beyond.The Biochemical journal · 2026Review
- Impact of cellular proteases on the function of antiviral antibodies.Journal of virology · 2026Review
- Structural insights into proprotein convertase activation facilitate the engineering of highly specific furin inhibitors.Nature communications · 2025Article
- Protease engineering: Approaches, tools, and emerging trends.Biotechnology advances · 2025Review
- Host proteases: key regulators in viral infection and therapeutic targeting.Frontiers in immunology · 2025Review
- Passive Immunisation in the Treatment of Infectious Diseases Related to Highly Potent Bacterial Toxins.Biomedicines · 2024Review
- Screening of Small-Molecule Libraries Using SARS-CoV-2-Derived Sequences Identifies Novel Furin Inhibitors.International journal of molecular sciences · 2024Article
- Inhibition of Infectious HIV-1 Production by Rerouting the Cellular Furin Inhibitor Serpin B8.Journal of virology · 2023Article
- Review
- Nanobody-based binding assay for the discovery of potent inhibitors of CFTR inhibitory factor (Cif).Analytica chimica acta · 2019Article
- Furin-mediated protein processing in infectious diseases and cancer.Clinical & translational immunology · 2019Review
- Proprotein convertase inhibition: Paralyzing the cell's master switches.Biochemical pharmacology · 2017Review
- The proprotein convertase furin is required to maintain viability of alveolar rhabdomyosarcoma cells.Oncotarget · 2016Article
- Structure of the unliganded form of the proprotein convertase furin suggests activation by a substrate-induced mechanism.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- The structure of a furin-antibody complex explains non-competitive inhibition by steric exclusion of substrate conformers.Scientific reports · 2016Article
- Liver-Specific Inactivation of the Proprotein Convertase FURIN Leads to Increased Hepatocellular Carcinoma Growth.BioMed research international · 2015Article
- Interactions between metal-binding domains modulate intracellular targeting of Cu(I)-ATPase ATP7B, as revealed by nanobody binding.The Journal of biological chemistry · 2014Article
- X-ray structures of human furin in complex with competitive inhibitors.ACS chemical biology · 2014Article
- Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
The PC (proprotein convertase) furin cleaves a large variety of proproteins and hence plays a major role in many pathologies. Therefore furin inhibition might be a good strategy for therapeutic intervention, and several furin inhibitors have been generated, although none are entirely furin-specific. To reduce potential side effects caused by cross-reactivity with other proteases, dromedary heavy-chain-derived nanobodies against catalytically active furin were developed as specific furin inhibitors. The nanobodies bound only to furin but not to other PCs. Upon overexpression in cell lines, they inhibited the cleavage of two different furin substrates, TGFβ (transforming growth factor β) and GPC3 (glypican 3). Purified nanobodies could inhibit the cleavage of diphtheria toxin into its enzymatically active A fragment, but did not inhibit cleavage of a small synthetic peptide-based substrate, suggesting a mode-of-action based on steric hindrance. The dissociation constant of purified nanobody 14 is in the nanomolar range. The nanobodies were non-competitive inhibitors with an inhibitory constant in the micromolar range as demonstrated by Dixon plot. Furthermore, anti-furin nanobodies could protect HEK (human embryonic kidney)-293T cells from diphtheria-toxin-induced cytotoxicity as efficiently as the PC inhibitor nona-D-arginine. In conclusion, these antibody-based single-domain nanobodies represent the first generation of highly specific non-competitive furin inhibitors.
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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.