3.4.21.69: Protein C (activated)
This is an abbreviated version!
For detailed information about Protein C (activated), go to the full flat file.
Word Map on EC 3.4.21.69
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3.4.21.69
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thrombosis
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venous
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leiden
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sepsis
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endothelial
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antithrombin
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thromboembolism
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thrombophilia
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clot
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thrombomodulin
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platelet
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procoagulant
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heparin
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arterial
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vein
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bleeding
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plasminogen
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hypercoagulable
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thromboplastin
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lupus
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fibrinogen
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fibrinolysis
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hemostatic
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viiia
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epcr
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intravascular
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contraceptive
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antiphospholipid
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antithrombotic
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prothrombotic
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fibrin
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k-dependent
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anticardiolipin
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d-dimers
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coagulopathy
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embolism
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prothrombinase
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amidolytic
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thrombin-antithrombin
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haemostasis
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par1
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profibrinolytic
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pharmacology
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goal-directed
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diagnostics
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drug development
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gamma-carboxyglutamic
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deep-vein
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time-based
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tafi
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hypofibrinolysis
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thromboprophylaxis
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medicine
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protac
- 3.4.21.69
- thrombosis
- venous
- leiden
- sepsis
- endothelial
- antithrombin
- thromboembolism
- thrombophilia
- clot
- thrombomodulin
- platelet
-
procoagulant
- heparin
- arterial
- vein
-
bleeding
- plasminogen
-
hypercoagulable
- thromboplastin
-
lupus
- fibrinogen
-
fibrinolysis
-
hemostatic
- viiia
- epcr
-
intravascular
-
contraceptive
-
antiphospholipid
-
antithrombotic
-
prothrombotic
- fibrin
-
k-dependent
-
anticardiolipin
-
d-dimers
- coagulopathy
- embolism
- prothrombinase
-
amidolytic
-
thrombin-antithrombin
-
haemostasis
- par1
-
profibrinolytic
- pharmacology
-
goal-directed
- diagnostics
- drug development
-
gamma-carboxyglutamic
-
deep-vein
-
time-based
- tafi
-
hypofibrinolysis
-
thromboprophylaxis
- medicine
- protac
Reaction
degradation of blood coagulation factors Va and VIIIa =
Synonyms
Activated blood coagulation factor XIV, Activated protein C, anticoagulant activated protein C, anticoagulant protein C/protein S system, anticoagulant serine protease-activated protein C, anticoagulant-activated protein C, APC, Autoprothrombin II-A, Autoprothrombin IIA, Blood coagulation factor XIV, Blood-coagulation factor XIV, activated, Blood-coagulation factor XIVa, ghrelin endopeptidase, GSAPC, hAPC, PROC, Protein Ca, rhAPC
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Application
Application on EC 3.4.21.69 - Protein C (activated)
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diagnostics
endogenous protein C levels positively correlate with a positive outcome in patients with severe sepsis
drug development
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at therapeutically relevant concentrations, activated protein C suppresses the release of interleukin-6 from stimulated human neutrophils and inhibited chemotaxis, without affecting the respiratory burst, apoptosis, and expression of other key cytokines. These effects are likely to be cell-type specific but may have implications for treatment of patients with activated protein C
medicine
pharmacology
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activated protein C might be useful as therapeutic agent in sepsis, clinical trials, overview
medicine
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low molecular weight activated protein C inhibitors might be useful as potential treatment for hemophilic disorders
medicine
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the activated protein C exhibits anti-inflammatory and cytoprotective properties, which may contribute to the beneficial effect of APC in treating severe sepsis patients, a higher incidence of bleeding because of its anticoagulant function is a major drawback of APC as an effective anti-inflammatory drug
medicine
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the enzyme is used for treatment of sepsis in humans, but the enzyme shows harmful side effects by causing life-threatening hemorrhage, clinical trials, overview
medicine
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the recombinant human activated protein C is useful for the postexposure treatment of Ebola hemorrhagic fever, clinical studies in rhesus monkeys, overview
medicine
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a low level of APC-protein C inhibitor complex in plasma may be associated with an increased risk of arteriovenous fistula/graft failure in hemodialysis patients
medicine
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activated protein C-protein C inhibitor complex correlates with abdominal aortic aneurysm diameter, body mass index, and age. Activated protein C-C-protein C inhibitor complex does not correlate with abdominal aortic aneurysm growth rate. Effect of the abdominal aortic aneurysm diameter on the protein C inhibitor complex concentration differs between men and women
medicine
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important role for the aPC/endothelial protein C receptor pathway in reducing metastasis via inhibition of tumor cell adhesion and transmigration
medicine
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leukocyte integrins are cellular receptors for recombinant activated protein C and the interaction decreases neutrophil recruitment into tissues, providing a potential mechanism by which recombinant human APC may protect against sepsis
medicine
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recombinant activated protein C-mediated upregulation of interleukin-10 reduces tissue factor in circulating monocytes. Part of the protective effect of recombinant activated protein C therapy may reflect the ability of recombinant activated protein C to dampen the proinflammatory and procoagulant potential of activated monocytes
medicine
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activated protein C is a natural protein with anticoagulant and immunomodulatory effects, and its recombinant version is approved by the U.S. Food and Drug Administration to treat severe sepsis
medicine
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possible therapeutic applications of the enzyme mutant G216D, that has no catalytic activity but retains its antiseptic function without anticoagulant side effects
medicine
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the enzyme might have therappeutic potential in treatment of Alzheimer's disease
medicine
enzyme mutant 3K3A-APC appears to be safe in ischemic stroke patients and reduced bleeding in the brain after tissue plasminogen activator therapy in a recent phase 2 clinical trial. Studies using human fetal neural stem and progenitor cells show that 3K3A-APC promotes neurogenesis in vitro as well as in vivo in the murine middle cerebral artery occlusion stroke model. 3K3A-APC appears to be safe in ischemic stroke patients and reduced bleeding in the brain after tissue plasminogen activator therapy in a recent phase 2 clinical trial. Enzyme mutant 3K3A-APC may potentially be used for late treatment of stroke in patients in ongoing phase 1 (NCT01151124) and phase 2 (NCT02117635) clinical trials that involve directly injecting manufactured NSCs into the brain of patients that remain moderately to severely disabled following an ischemic stroke
medicine
possible effects of APC administration may include attenuation of the proinflammatory cytokine storm, re-balancing dysregulated haemostasis or degradation of cytotoxic extracellular histones that circulate during sepsis. Worldwide evaluation in severe sepsis (PROWESS) study demonstrated that recombinant APC (Xigris) administration reduces the relative risk of death compared with patients treated with a placebo (28 day mortality rate of 24.7% in individuals treated with recombinant APC, compared with 30.8% treated with placebo), prompting food and drug administration (FDA) approval for the application of Xigris in the treatment of severe sepsis. Subsequent concerns as to the efficacy and safety profile of Xigris prompted the PROWESS SHOCK trial that, in contrast with the original PROWESS study, indicated a lack of efficacy for Xigris in reducing the risk of death in severe sepsis patients, resulting in market withdrawal. The broad cytoprotective functions of APC on multiple cell types mean APC continues to lend itself to therapeutic applications, overview
medicine
protective effect of recombinant APC administration in animals subject to Escherichia coli-induced sepsis. Possible effects of APC administration may include attenuation of the proinflammatory cytokine storm, re-balancing dysregulated haemostasis or degradation of cytotoxic extracellular histones that circulate during sepsis. Successful pre-clinical animal studies indicate that the neuroprotective effects of recombinant APC do not require anti-coagulant activity for therapeutic benefit to be achieved
medicine
protective effect of recombinant APC administration in animals subject to Escherichia coli-induced sepsis. Possible effects of APC administration may include attenuation of the proinflammatory cytokine storm, re-balancing dysregulated haemostasis or degradation of cytotoxic extracellular histones that circulate during sepsis. Successful pre-clinical animal studies indicate that the neuroprotective effects of recombinant APC do not require anti-coagulant activity for therapeutic benefit to be achieved. The bleeding risk associated with the use of recombinant APC in the treatment of severe sepsis and apparent lack of requirement for APC anti-coagulant function for protective activity in murine endotoxemia and stroke models prompted the development of APC variants with selectively diminished anti-coagulant activity. APC variants that possess limited anti-coagulant function but normal cytoprotective signalling activity represent a potentially safer alternative to recombinant wild-type APC in disease settings in which APC has been shown to be protective
medicine
Recombinant APC and/or its analogues with reduced by over 90% anticoagulant activity such as mutant 3K3A-APC (K191A/K192A/K193A), engineered to reduce APC-associated bleeding risk while retaining normal cell signaling activity, have shown benefits in preclinical models of ischemic stroke, brain trauma, multiple sclerosis, amyotrophic lateral sclerosis, sepsis, ischemic/reperfusion injury of heart, kidney and liver, pulmonary, kidney and gastrointestinal inflammation, diabetes, and lethal body radiation. Enzyme mutant 3K3A-APC stimulates neuronal production by human neural stem/progenitor cells (NSCs) in vitro via a PAR1-PAR3-sphingosine-1-phosphate receptor 1-Akt pathway, suggesting the potential for APC-based treatment as a strategy for structural repair in the human central nervous system. Late post-ischemic treatment of C57BL/6J mice with 3K3A-APC stimulates neuronal production by transplanted human NSCs, promotes circuit restoration, and improves functional recovery
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activated protein C is a natural protein with anticoagulant and immunomodulatory effects, and its recombinant version is approved by the U.S. Food and Drug Administration to treat severe sepsis
pharmacology
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activated protein C is approved by the Food and Drug Administration as drug for severe sepsis