ArticleNeoplasia (New York, N.Y.)2007
PEGylated DX-1000: pharmacokinetics and antineoplastic activity of a specific plasmin inhibitor.
Article in Neoplasia (New York, N.Y.), 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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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.
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Who cites it
13 citing papers in PubMed, 35 citations in OpenAlex.
- Enhanced Antifibrinolytic Efficacy of a Plasmin-Specific Kunitz-Inhibitor (60-Residue Y11T/L17R with C-Terminal IEK) of Human Tissue Factor Pathway Inhibitor Type-2 Domain1.Journal of clinical medicine · 2020Article
- Measurement of Bradykinin Formation and Degradation in Blood Plasma: Relevance for Acquired Angioedema Associated With Angiotensin Converting Enzyme Inhibition and for Hereditary Angioedema Due to Factor XII or Plasminogen Gene Variants.Frontiers in medicine · 2020Article
- Increased fibrinolysis-induced bradykinin formation in hereditary angioedema confirmed using stored plasma and biotechnological inhibitors.BMC research notes · 2019Article
- Disulfide engineering of human Kunitz-type serine protease inhibitors enhances proteolytic stability and target affinity toward mesotrypsin.The Journal of biological chemistry · 2019Article
- Combinatorial protein engineering of proteolytically resistant mesotrypsin inhibitors as candidates for cancer therapy.The Biochemical journal · 2016Article
- Plasmin regulation through allosteric, sulfated, small molecules.Molecules (Basel, Switzerland) · 2015Article
- Recent advances on plasmin inhibitors for the treatment of fibrinolysis-related disorders.Medicinal research reviews · 2014Review
- Biochemical and structural insights into mesotrypsin: an unusual human trypsin.International journal of biochemistry and molecular biology · 2013Review
- The P(2)' residue is a key determinant of mesotrypsin specificity: engineering a high-affinity inhibitor with anticancer activity.The Biochemical journal · 2011Article
- Determinants of affinity and proteolytic stability in interactions of Kunitz family protease inhibitors with mesotrypsin.The Journal of biological chemistry · 2010Article
- The War on Cancer rages on.Neoplasia (New York, N.Y.) · 2009Article
- Drug development against metastasis-related genes and their pathways: a rationale for cancer therapy.Biochimica et biophysica acta · 2008Review
- Neoplasia: the second decade.Neoplasia (New York, N.Y.) · 2008Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Novel inhibitors of the urokinase-mediated plasminogen (plg) activation system are potentially of great clinical benefit as anticancer treatments. Using phage display, we identified DX-1000 a tissue factor pathway inhibitor-derived Kunitz domain protein which is a specific high-affinity inhibitor of plasmin (pln) (K(i) = 99 pM). When tested in vitro, DX-1000 blocks plasmin-mediated pro-matrix metalloproteinase-9 (proMMP-9) activation on cells and dose-dependently inhibits tube formation, while not significantly affecting hemostasis and coagulation. However, this low-molecular weight protein inhibitor ( approximately 7 kDa) exhibits rapid plasma clearance in mice and rabbits, limiting its potential clinical use in chronic diseases. After site-specific PEGylation, DX-1000 retains its activity and exhibits a decreased plasma clearance. This PEGylated derivative is effective in vitro, as well as potent in inhibiting tumor growth of green fluorescent protein (GFP)-labeled MDA-MB-231 cells. 4PEG-DX-1000 treatment causes a significant reduction of urokinase-type plasminogen activator (uPA) and plasminogen expressions, a reduction of tumor proliferation, and vascularization. 4PEG-DX-1000 treatment significantly decreases the level of active mitogen-activated protein kinase (MAPK) in the primary tumors and reduces metastasis incidence. Together, our results demonstrate the potential value of plasmin inhibitors as therapeutic agents for blocking breast cancer growth and metastasis.
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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.