Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

p-Carbethoxyphenyl episol-guanidinocaproate and p-(p'-guanidinobenzoyloxy)-phenyl derivatives were prepared, and their inhibitory effects on trypsin, plasmin, plasma kallikrein, thrombin, C1r- and C1 esterase were examined. Among the various inhibitors tested, p-nitrophenyl p'-guanidinobenzoate, N,N-dimethylamino p-(p'-guanidinobenzoyloxy)-benzoyl glycolate and N,N-dimethylamino p-(p'-guanidinobenzoyloxy)-benzilcarbonyloxy glycolate were the most effective inhibitors of trypsin, plasmin, plasma kallikrien and thrombin, and they strongly inhibited the esterolytic activities of C1r- and C1 esterase.
 ...
PMID:Synthetic inhibitors of trypsin, plasmin, kallikrein, thrombin, C1r-, and C1 esterase. 14 65

An inhibitor of procoagulant and fibrinolytic enzymes was derived from cabbage seeds by a procedure using acetone precipitation, ion-exchange chromatography, and gel filtration. The cabbage seed inhibitor was a 10-Kd monomeric protein with intrachain disulfide bonds. This preparation prevented clot formation in whole blood and blocked the ability of thrombin to induce clot formation in plasma and to induce platelet aggregation. A number of proteases were inhibited, as demonstrated by using purified enzymes in amidolytic assays. Tight-binding inhibition was observed for activated Stuart factor (factor Xa) and plasmin. Inhibition of thrombin and activated Hageman factor (factor XIIa) was observed with a molar excess of inhibitor. No inhibition was detected for activated plasma thromboplastin antecedent (factor XIa), plasma kallikrein, or C1 esterase. Reaction progress curves for trypsin indicated slow, tight-binding inhibition, with an apparent inhibition constant in the nanomolar range or less. The electrophoretic mobility of trypsin was altered by the inhibitor in nondenaturing polyacrylamide gel electrophoresis (PAGE) but not in sodium dodecyl sulfate (SDS)-PAGE, indicating noncovalent bonding. Only partial reversal of trypsin inhibition could be demonstrated by washing the inhibitor from enzyme immobilized on solid beads. A dot-blot technique with cabbage seed inhibitor was capable of detecting 10 ng nitrocellulose-bound trypsin. The dot-blot technique also appeared capable of detecting plasmin. These findings demonstrated the potential utility of this inhibitor as a probe for detection of tightly bound proteases. In summary, cabbage seed extracts contain an inhibitor with activity toward a broad range of proteases important to hemostasis. To our knowledge, this agent represents the first inhibitor isolated from a plant source that inhibits thrombin.
 ...
PMID:Cabbage seed protease inhibitor: a slow, tight-binding inhibitor of trypsin with activity toward thrombin, activated Stuart factor (factor Xa), activated Hageman factor (factor XIIa), and plasmin. 213

Acute pancreatitis (AP) is believed to result from intraparenchymal activation of trypsin and other digestive enzymes within the pancreas followed by autodigestion of the gland. Gabexate mesilate (FOY), a synthetic guanidino acid ester exhibiting potent and versatile inhibitory actions on a number of proteinases (e.g., trypsin, kallikrein, C1-r, C1 esterase, plasmin, thrombin, phospholipase A2), was examined for its ability to protect the rat pancreas against development of AP induced by pharmacological doses of ceruletide (CRT). Rats were i.v. infused for 6 h with either CRT (5 micrograms/kg/h) or CRT + FOY (50 mg/kg/h). In FOY-treated rats the serum amylase and trypsinogen concentrations were reduced by 60 and 80%, respectively, compared to rats infused with CRT alone. Histologically, the extent of acinar cell vacuolization in the pancreas was significantly reduced and interstitial edema, although not assessed by quantitative morphometric techniques, appeared to be qualitatively lessened in the FOY-treated rats. The ability of FOY to inhibit significantly AP produced by supramaximal doses of CRT, coupled with its inhibitory properties on components of the coagulation and complement cascades, stress the importance of continued research on this compound as a potential therapeutic agent for treatment of AP and its systemic sequelae.
 ...
PMID:Gabexate mesilate (FOY) protects against ceruletide-induced acute pancreatitis in the rat. 244 41

The effect of human skin mast cell tryptase on human plasma proenzymes (prothrombin, coagulation factor XII, complement C1s, protein C and plasminogen) was investigated. Tryptase had no effect on these proenzymes, when incubated with them at 37 degrees C for up to 90 min, as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by the ability to hydrolyze specific peptide p-nitroanilide substrates. After prolonged treatment with tryptase, proenzymes could be fully activated with their specific activators. The results indicate that tryptase neither activates these plasma proenzymes nor inactivates the corresponding active enzymes. As a positive control, the tryptase preparation was also incubated with human fibrinogen and rat thymus histones. Prolonged treatment with tryptase increased the thrombin-induced clotting time of fibrinogen. Tryptase also efficiently hydrolyzed histone H1 from rat thymus. Histones H3/H2B and H2A were hydrolyzed less efficiently than H1, and no hydrolysis of histone H4 by tryptase was detected under the experimental conditions.
 ...
PMID:Effect of human mast cell tryptase on human plasma proenzymes. 253 Jan 78

Suspensions of peripheral blood mononuclear cells (PBMC), monocytes, T or B lymphocytes, platelets or granulocytes, and cell-depleted supernatant fluids of these suspensions inhibited activation of Hageman factor (HF, Factor XII) by ellagic acid, a property not shared by erythrocytes. PBMC also inhibited HF activation by glass or sulfatides. Contaminating platelets may have contributed to inhibition by PBMC. Elaboration of agents inhibiting HF activation required metabolically active cells. The inhibitor(s) in PBMC supernates were not identified with known agents, but had properties of a nonenzymatic protein. PBMC supernates did not contain fibrinogen, nor alter the thrombin, prothrombin, or partial thromboplastin times of normal plasma, amidolysis by activated plasma thromboplastin antecedent (Factor XIa) or activated Stuart factor (Factor Xa) or esterolysis by C1 (C1 esterase); they inhibited plasmin minimally. These experiments suggest that peripheral blood cells may impede intravascular coagulation. Whether this property helps maintain the fluidity of blood is unclear.
 ...
PMID:Inhibition of the activation of Hageman factor (factor XII) by peripheral blood cells. 349 41

1. The inhibition by suramin of complement components, and of blood clotting, fibrinolytic, and plasma kinin forming factors depended on the conditions of the assay and on the substrates used.2. Haemolysis by complement was more effectively inhibited in red blood cell suspensions, than in agarose gel plates. In esterolytic tests, the activation of component 1 (C1) to C1 esterase was significantly inhibited by 0.1-0.3 mM suramin, and the activity of C1 esterase by 0.5 mM suramin.3. Part of the anticoagulant effect of suramin is due to inhibition of the action of thrombin on fibrinogen.4. Suramin did not inhibit fibrin degradation by the fibrinolytic system in plasma. In esterolytic tests, the activation of plasminogen was more potently inhibited than the activity of plasmin.5. Activation of plasma kallikrein, measured either by kinin formation or by esterolysis, was inhibited by 0.1-0.3 mM suramin. Active plasma kallikrein was inhibited by 0.3-0.5 mM suramin. Pancreatic kallikrein was weakly inhibited, and urinary kallikrein not at all.
 ...
PMID:Effects of suramin on complement, blood clotting, fibrinolysis and kinin formation. 478 38

We have studied the effects of murine alpha-1-antitrypsin and contrapsin, a new trypsin inhibitor (Takahara, H. and Sinohara, H. (1982) J. Biol. Chem. 257, in press), on several serine proteases participating in blood clotting, fibrinolysis, kinin generation, and complement activation. Bovine plasmin and human plasma kallikrein were inactivated by contrapsin but not by alpha-1-antitrypsin, whereas bovine alpha-thrombin and porcine pancreas kallikrein were inhibited by alpha-1-antitrypsin but not by contrapsin. Heparin protected thrombin from inactivation by alpha-1-antitrypsin. Both inhibitors had virtually no effects on canine C1 esterase.
 ...
PMID:Mouse plasma trypsin inhibitors: inhibitory spectrum of contrapsin and alpha-1-antitrypsin. 621 66

FUT-175 (6 amidino-2-naphthyl-4-guanidino benzoate-dimethanesulfonate), a new synthetic protease inhibitor, inhibits the enzyme activities of various proteases, such as Clr, C1 esterase, thrombin, kallikrein, plasmin and trypsin. FUT-175 strongly inhibited complement-medicated hemolysis via the classical and alternative pathways. The effects of FUT-175 on various immunological reactions in vivo were studied. The minimal effective dose of FUT-175 in systemic Forssman shock in guinea pigs was 6.25 mg/kg i.p. and 25 mg/kg p.o. In passive Arthus reactions in rats, the effective dose was 25 mg/kg i.p. and 250 mg/kg p.o. FUT-175 also inhibited other immunological reactions, such as passive cutaneous anaphylaxis and delayed hypersensitivity. Furthermore, at a dose of 25 mg/kg i.p. it strongly protected mice from death in endotoxin shock.
 ...
PMID:Inhibition of various immunological reactions in vivo by a new synthetic complement inhibitor. 621 61

p-Guanidinobenzoate derivates were prepared and their inhibitory effects on trypsin, plasmin, pancreatic kallikrein, plasma kallikrein, thrombin, C1r and C1 esterase were examined. Among the various inhibitors tested, 6'-amidino-2-naphthyl-4-guanidinobenzoate dihydrochloride, 4-(beta-amidinoethenyl)phenyl-4-guanidinobenzoate dimethanesulfonate and 4-amidino-2-benzoylphenyl-4-guanidinobenzoate dimethanesulfonate were the most effective inhibitors of trypsin, plasmin, pancreatic kallikrein. plasma kallikrein and thrombin and they strongly inhibited the esterolytic activities of C1r and C1 esterase, and then strongly inhibited complement-mediated hemolysis.
 ...
PMID:New synthetic inhibitors of C1r, C1 esterase, thrombin, plasmin, kallikrein and trypsin. 627 Dec 24

C1-Inhibitor (Berinert, C1 INH), a 104 kDa protein, inhibits complement components (C1 esterase) as well as enzymes of the contact phase of coagulation (Factor XII, Factor XI) and kallikrein, thus regulating kinin generation. C1 INH is used for the treatment of the hereditary angioneurotic edema. This paper will give a survey about the evidence in recent literature concerning the potential efficacy of the compound on other diseases associated with shock, capillary leakage and inflammation as well. In our own experiments we evaluated whether the compound could influence acute inflammatory reactions or the severe systemic inflammatory response syndrome (SIRS) as a consequence of an experimental septic shock. To prevent the sepsis-induced DIC we co-infused the thrombin inhibitors AT III or rec. hirudin in combination with C1 INH. Coinfusion of C1-inhibitor (50-200 U/kg x h) with either rec. hirudin or AT III significantly improved survival rate compared to thrombin inhibitor alone.
 ...
PMID:Influence of C1-inhibitor on inflammation, edema and shock. 817 80


1 2 Next >>