Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q9UID3 (FFR)
 233 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The importance of activated factor VII (FVIIa) in coagulation initiated by tissue factor (TF) was illustrated by competition of active site-inhibited FVIIa (FFR-FVIIa; FVIIa treated with D-Phe-Phe-Arg-chloromethyl ketone) with FVIIa in various cell-based assays mimicking TF-initiated coagulation. FFR-FVIIa inhibited the overall initiation process as measured by platelet activation and large-scale thrombin generation on the activated platelet surface. When the individual steps in the initiation process were separated, FFR-FVIIa affected only the reactions taking place on TF-bearing cells, demonstrating that FVIIa takes part only in the very first step in the initiation process. The dissociation constant (Kd) for FVIIa binding to TF and the inhibition constant (Ki) for FFR-FVIIa competing with FVIIa in binding to TF, measured in a factor X activation assay, were both around 10 pmol/l, showing that FVIIa and FFR-FVIIa bound to TF in the extrinsic pathway tenase complex with the same affinity.
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PMID:The effects of activated factor VII in a cell-based model for tissue factor-initiated coagulation. 981 25

Originally isolated from a haematophagous hookworm, recombinant nematode anticoagulant protein c2 (rNAPc2) is an 85-amino acid protein with potent anticoagulant properties. Unlike conventional anticoagulants that attenuate blood coagulation via inhibition of thrombin or activated factor X (FXa) at the downstream portion of the cascade, rNAPc2 is a potent inhibitor of the activated factor VII/tissue factor complex (FVIIa/TF), the key physiological initiator of blood coagulation. Its mechanism of action requires prerequisite binding to circulating FXa or zymogen factor X (FX) to form a binary complex prior to its interaction and inhibition of membrane-bound FVIIa/TF. The binding of rNAPc2 to FX results in an elimination half-life of longer than 50 h following either subcutaneous or intravenous administration. Recombinant NAPc2, like other inhibitors of FVIIa/TF including tissue factor pathway inhibitor (TFPI) and active site-blocked FVIIa (ASIS, FFR-rFVIIa or FVIIai), may have a promising role in the prevention and treatment of venous and arterial thrombosis, as well as potential efficacy in the management of disseminated intravascular coagulopathies because of their potent and selective inhibition of FVIIa/TF.
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PMID:Recombinant nematode anticoagulant protein c2 and other inhibitors targeting blood coagulation factor VIIa/tissue factor. 1297 70

Tissue factor (TF) is believed to play an important role in coagulation, inflammation, angiogenesis and wound healing as well as in tumor growth and metastasis. To facilitate in vivo studies in experimental murine models, we have produced recombinant murine factor VII (FVII) and the ectodomain of murine TF, TF(1-223). Murine FVII was activated to FVIIa with human factor Xa and upon reaction with FFR-chloromethyl ketone converted into an active site-blocked TF antagonist, FFR-FVIIa. The activity of murine FVIIa was characterized in factor X activation assays as well as in clot assays with murine and human thromboplastin in murine and human plasma. In these assays murine FVIIa exhibited a specific activity equivalent to or higher than human FVIIa. Further analysis showed that murine FVIIa binds with high affinity to both murine and human TF, whereas the association of human FVIIa to murine TF is about three orders of magnitude weaker than the association to human TF. This difference was further emphasized by the effect of murine-and human FFR-FVIIa on bleeding in an in vivo mouse model. Intra-peritoneal administration of 1 mg/kg murine FFR-FVIIa significantly prolonged the tail-bleeding time, whereas no effect on bleeding was observed with a 25-times higher dose of the human FFR-FVIIa. Together, these data confirms the notion of poor species compatibility between human FVII and murine TF and emphasizes the requirement for autologous FVIIa in studies on the role of the TF in experimental in vivo pharmacology.
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PMID:Characterization of recombinant murine factor VIIa and recombinant murine tissue factor: a human-murine species compatibility study. 1585 Jun 11