Target type: biologicalprocess
Any process that increases the rate, frequency or extent of plasminogen activation. Plasminogen activation is the process in which plasminogen is processed to plasmin. [GOC:BHF, GOC:dph, GOC:tb]
Positive regulation of plasminogen activation is a critical step in the breakdown of fibrin clots, a process essential for wound healing, tissue remodeling, and the maintenance of blood vessel patency. It involves a complex interplay of proteins and enzymes that activate plasminogen, the inactive precursor of plasmin, a potent fibrinolytic enzyme. The process is tightly regulated to prevent excessive fibrinolysis and ensure appropriate clot dissolution.
**Key Players:**
* **Plasminogen:** The inactive precursor of plasmin, found in plasma and tissues.
* **Plasmin:** The active enzyme that degrades fibrin, a key component of blood clots.
* **Tissue plasminogen activator (tPA):** A serine protease released from endothelial cells that binds to fibrin and activates plasminogen to plasmin.
* **Urokinase-type plasminogen activator (uPA):** Another serine protease, predominantly found in the extracellular matrix, that activates plasminogen.
* **Plasminogen activator inhibitor-1 (PAI-1):** A major inhibitor of tPA and uPA, controlling the extent of plasminogen activation.
**Mechanism:**
1. **Activation of Plasminogen:** tPA or uPA bind to fibrin and plasminogen, bringing them into close proximity.
2. **Cleavage:** The bound activator cleaves plasminogen, converting it to the active enzyme, plasmin.
3. **Fibrinolysis:** Plasmin degrades fibrin, breaking down the clot and allowing for tissue repair and restoration of blood flow.
**Regulation:**
* **Positive Regulation:** Various factors enhance plasminogen activation, including:
* **Tissue injury:** Trauma, inflammation, or other injuries trigger the release of tPA and uPA.
* **Hormones:** Estrogen, testosterone, and other hormones can influence plasminogen activation.
* **Thrombin:** This enzyme, involved in coagulation, can activate tPA.
* **Negative Regulation:** PAI-1, a key inhibitor, controls the extent of plasminogen activation. Other factors, such as α2-antiplasmin, also contribute to inhibiting fibrinolysis.
**Significance:**
Positive regulation of plasminogen activation is crucial for maintaining a balance between coagulation and fibrinolysis, ensuring appropriate clot formation and dissolution. Dysregulation of this process can lead to various pathologies, including thrombosis (uncontrolled clotting) and hemorrhage (excessive bleeding). Understanding the intricate mechanisms governing plasminogen activation provides valuable insights into the complex interplay of coagulation and fibrinolysis, paving the way for targeted therapies and interventions for thromboembolic disorders.'
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Protein | Definition | Taxonomy |
---|---|---|
Protein S100-A10 | A protein S100-A10 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P60903] | Homo sapiens (human) |
Annexin A2 | An annexin A2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P07355] | Homo sapiens (human) |
Alpha-enolase | An alpha-enolase that is encoded in the genome of human. [PMID:17968930, SALO:AJ] | Homo sapiens (human) |
Serine protease hepsin | A serine protease hepsin that is encoded in the genome of human. [PRO:DNx, UniProtKB:P05981] | Homo sapiens (human) |
Coagulation factor XII | A coagulation factor XII that is encoded in the genome of human. [PRO:DNx, UniProtKB:P00748] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
4-methylumbelliferyl acetate | 4-methylumbelliferyl acetate : An acetate ester consiting of umbelliferone carrying a 7-O-acetyl group. | acetate ester; coumarins | plant metabolite |
diacetyl | butane-2,3-dione : An alpha-diketone that is butane substituted by oxo groups at positions 2 and 3. It is a metabolite produced during the malolactic fermentation. | alpha-diketone | Escherichia coli metabolite; Saccharomyces cerevisiae metabolite |
6,7-dichloroquinoxaline-2,3-dione | quinoxaline derivative | ||
tacrine | tacrine : A member of the class of acridines that is 1,2,3,4-tetrahydroacridine substituted by an amino group at position 9. It is used in the treatment of Alzheimer's disease. Tacrine: A cholinesterase inhibitor that crosses the blood-brain barrier. Tacrine has been used to counter the effects of muscle relaxants, as a respiratory stimulant, and in the treatment of Alzheimer's disease and other central nervous system disorders. | acridines; aromatic amine | EC 3.1.1.7 (acetylcholinesterase) inhibitor |
ethacridine | Ethacridine: A topically applied anti-infective agent. | acridines | |
camostat | camostat : A benzoate ester resulting from the formal condensation of the carboxy group of 4-guanidinobenzoic acid with the hydroxy group of 2-(dimethylamino)-2-oxoethyl (4-hydroxyphenyl)acetate. It is a potent inhibitor of the human transmembrane protease serine 2 (TMPRSS2) and its mesylate salt is currently under investigation for its effectiveness in COVID-19 patients. | benzoate ester; carboxylic ester; diester; guanidines; tertiary carboxamide | anti-inflammatory agent; anticoronaviral agent; antifibrinolytic drug; antihypertensive agent; antineoplastic agent; antiviral agent; serine protease inhibitor |
benzophenone | benzophenone : The simplest member of the class of benzophenones, being formaldehyde in which both hydrogens are replaced by phenyl groups. | benzophenones | photosensitizing agent; plant metabolite |
gabexate | Gabexate: A serine proteinase inhibitor used therapeutically in the treatment of pancreatitis, disseminated intravascular coagulation (DIC), and as a regional anticoagulant for hemodialysis. The drug inhibits the hydrolytic effects of thrombin, plasmin, and kallikrein, but not of chymotrypsin and aprotinin. | benzoate ester | |
nafamostat | nafamostat: inhibitor of trypsin, plasmin, pancreatic kallikrein, plasma kallikrein & thrombin; strongly inhibits esterolytic activities of C1r & C1 esterase complement-mediated hemolysis; antineoplastic | benzoic acids; guanidines | |
quinone | 1,4-benzoquinone : The simplest member of the class of 1,4-benzoquinones, obtained by the formal oxidation of hydroquinone to the corresponding diketone. It is a metabolite of benzene. benzoquinone : The simplest members of the class of benzoquinones, consisting of cyclohexadiene which is substituted by two oxo groups. quinone : Compounds having a fully conjugated cyclic dione structure, such as that of benzoquinones, derived from aromatic compounds by conversion of an even number of -CH= groups into -C(=O)- groups with any necessary rearrangement of double bonds (polycyclic and heterocyclic analogues are included). | 1,4-benzoquinones | cofactor; human xenobiotic metabolite; mouse metabolite |
acenaphthenequinone | acenaphthoquinone : An orthoquinone that is the 1,2-dioxo derivative of acenaphthene. | orthoquinones | chain carrier; epitope |
9,10-phenanthrenequinone | 9,10-phenanthrenequinone: structure | phenanthrenes | |
5-bromoisatin | indoles | anticoronaviral agent | |
isatin | tribulin: endogenous MONOAMINE OXIDASE inhibitory activity extractable into ethyl acetate found in brain and many mammalian tissues and fluids; ISATIN is a major component; produced in excess following alcohol withdrawal; | indoledione | EC 1.4.3.4 (monoamine oxidase) inhibitor; plant metabolite |
chloranil | Chloranil: A quinone fungicide used for treatment of seeds and foliage. tetrachloro-1,4-benzoquinone : A member of the class of 1,4-benzoquiones that is 1,4-benzoquinone in which all four hydrogens are substituted by chlorines. | 1,4-benzoquinones; organochlorine compound | EC 2.7.1.33 (pantothenate kinase) inhibitor; metabolite |
benzoin | benzoins; secondary alpha-hydroxy ketone | EC 3.1.1.1 (carboxylesterase) inhibitor | |
dibenzoylmethane | dibenzoylmethane : A beta-diketone that is acetylacetone (acac) in which both methyl groups have been replaced by phenyl groups. It is a minor constituent of the root extract of licorice (Glycyrrhiza glabra) and exhibits antimutagenic and anticancer effects. | aromatic ketone; beta-diketone | antimutagen; antineoplastic agent; metabolite |
benzil | benzil : An alpha-diketone that is ethane-1,2-dione substituted by phenyl groups at positions 1 and 2 respectively. benzil: structure | alpha-diketone; aromatic ketone | |
1,3-cyclohexanedione | 1,3-cyclohexanedione: structure cyclohexane-1,3-dione : A cyclohexanedione carrying oxo substituents at positions 1 and 3. | beta-diketone; cyclohexanedione | |
dibromsalicil | dibromsalicil: brominated salicyclic acid deriv; antiplaque antiseptic | ||
1,2-naphthoquinone | 1,2-naphthoquinone : The parent structure of the family of 1,2-naphthoquinones, in which the oxo groups of the quinone moiety are at positions 1 and 2 of the naphthalene ring. It is a metabolite of naphthalene and is found in diesel exhaust particles. naphthalene-1,2-dione: structure given in first source | 1,2-naphthoquinones | aryl hydrocarbon receptor agonist; carcinogenic agent |
1-acetylisatin | 1-acetylisatin: structure in first source | indoledione | |
1-phenyl-1,2-propanedione | 1-phenyl-1,2-propanedione : An alpha-diketone that consists of 1-phenylpropane bearing keto substituents at positions 1 and 2. It is found in coffee. 1-phenyl-1,2-propanedione: an oxoglutarate carrier antagonist | alpha-diketone; aromatic ketone | plant metabolite |
2,3-pentanedione | pentane-2,3-dione : An alpha-diketone that is pentane substituted at the 2- and 3-positions by oxo groups. | alpha-diketone; methyl ketone | flavouring agent |
5-methylisatin | 5-methylisatin: structure in first source | ||
n-methylisatin | N-methylisatin: structure given in first source | ||
9-amino-6-chloro-2-methoxyacridine | |||
acetylacetone | acetylacetone : A beta-diketone that is pentane in which the hydrogens at positions 2 and 4 are replaced by oxo groups. | beta-diketone | |
5-Methoxyisatin | indoles | anticoronaviral agent | |
3-methyl-1,2-cyclopentanedione | 3-methyl-1,2-cyclopentanedione: a peroxynitrite scavenger isolated from coffee extract; structure in first source | cyclic ketone | |
4-benzoylbenzoic acid | 4-carboxybenzophenone: a photosensitizer agent | ||
leupeptin | aldehyde; tripeptide | bacterial metabolite; calpain inhibitor; cathepsin B inhibitor; EC 3.4.21.4 (trypsin) inhibitor; serine protease inhibitor | |
1,10-phenanthroline-5,6-dione | 1,10-phenanthroline-5,6-dione: has antineoplastic, intercalating, and trypanocidal activities; structure given in first source | ||
2-chloranil | |||
3,5-di-tert-butyl-1,2-benzoquinone | |||
5-Chloro-1H-indole-2,3-dione | indoles | anticoronaviral agent | |
5-iodoisatin | 5-iodoisatin: structure in first source | indoles | anticoronaviral agent |
2,2-dimethoxy-2-phenylacetophenone | |||
anisoin | |||
hydrobenzoin | hydrobenzoin: structure in first source | ethanediol | |
gidazepam | gidazepam: prodrug for 7-bromo-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepine-2-one | ||
5-amidinoindole | |||
1,3-indandione | 1,2-indanedione: use for detection of latent fingerprints on porous surfaces; structure in first source | ||
dabigatran | dabigatran : An aromatic amide obtained by formal condensation of the carboxy group of 2-{[(4-carbamimidoylphenyl)amino]methyl}-1-methyl-1H-benzimidazole-5-carboxylic acid with the secondary amoino group of N-pyridin-2-yl-beta-alanine. The active metabolite of the prodrug dabigatran etexilate, it acts as an anticoagulant which is used for the prevention of stroke and systemic embolism. Dabigatran: A THROMBIN inhibitor which acts by binding and blocking thrombogenic activity and the prevention of thrombus formation. It is used to reduce the risk of stroke and systemic EMBOLISM in patients with nonvalvular atrial fibrillation. | aromatic amide; benzimidazoles; beta-alanine derivative; carboxamidine; pyridines | anticoagulant; EC 1.10.99.2 [ribosyldihydronicotinamide dehydrogenase (quinone)] inhibitor; EC 3.4.21.5 (thrombin) inhibitor |
5-Fluoroisatin | indoles | anticoronaviral agent | |
N-malonylanthranilic acid | dicarboxylic acid monoamide | ||
benzamidine | carboxamidinium ion | ||
phosphonoacetohydroxamate | phosphonoacetohydroxamic acid : The hydroxamate of phosphonoacetic acid. | hydroxamic acid; organic phosphonate | |
2-[2-[4-(2-fluorophenyl)-1-piperazinyl]-2-oxoethyl]-1,1-dioxo-1,2-benzothiazol-3-one | piperazines | ||
N-(3,4-dimethylphenyl)-2-[[5-[[(4,6-dimethyl-2-pyrimidinyl)thio]methyl]-4-(2-furanylmethyl)-1,2,4-triazol-3-yl]thio]acetamide | anilide | ||
1-(4-fluorophenyl)-2-[[4-(2-furanylmethyl)-5-(phenoxymethyl)-1,2,4-triazol-3-yl]thio]ethanone | aromatic ketone | ||
(4-Methyl-2-oxochromen-7-yl) furan-2-carboxylate | coumarins | anticoronaviral agent | |
3,4,5-trimethoxybenzoic acid [(3,5-dimethyl-4-oxo-1-cyclohexa-2,5-dienylidene)amino] ester | trihydroxybenzoic acid | ||
5-bromo-N-(4-propan-2-ylphenyl)-2-furancarboxamide | aromatic amide; furans | ||
2-furancarboxylic acid (2-acetyl-1-benzothiophen-3-yl) ester | carboxylic ester | ||
(5-amino-3-phenyl-1,2,4-triazol-1-yl)-(2-methoxyphenyl)methanone | triazoles | ||
(3-amino-1,2,4-triazol-4-yl)-(2,5-dimethylphenyl)methanone | benzoic acids | ||
3-[[(5-bromo-2-furanyl)-oxomethyl]amino]-2-methylbenzoic acid | aromatic amide; furans | ||
2-[[4-(4-methylphenyl)sulfonyl-1-piperazinyl]methyl]-4-propan-2-ylphenol | sulfonamide | ||
3-(1-piperidinylsulfonyl)-N-(2-thiazolyl)benzamide | sulfonamide | ||
2-[[2-(3,4-dimethylanilino)-2-oxoethyl]thio]acetamide | anilide | ||
2-furanyl-[4-(4-phenoxyphenyl)sulfonyl-1-piperazinyl]methanone | aromatic ether | ||
N-(4-fluorophenyl)-3-([1,2,4]triazolo[4,3-a]quinolin-1-ylthio)propanamide | quinolines | ||
LSM-32435 | triazolopyrimidines | ||
1-[1-ethyl-6-methyl-4-(4-phenyl-1-piperazinyl)-2-sulfanylidene-5-pyrimidinyl]ethanone | piperazines | ||
1-[(3,4-dichlorophenyl)methyl]indole-2,3-dione | indoles | ||
2-[[cyclohexyl(oxo)methyl]amino]acetic acid [2-(4-cyanoanilino)-2-oxoethyl] ester | depsipeptide | ||
6-(4-bromophenyl)-3-methyl-1-[2-(2H-tetrazol-5-yl)ethyl]-4-(trifluoromethyl)pyrazolo[3,4-b]pyridine | phenylpyridine | ||
2-ethoxy-N-[4-(2-pyrimidinylsulfamoyl)phenyl]acetamide | sulfonamide | ||
3-[[(4-tert-butylphenyl)-oxomethyl]amino]-1H-1,2,4-triazole-5-carboxylic acid methyl ester | benzamides | ||
3-(methoxymethyl)-2-benzofurancarboxylic acid [4-amino-6-(2-methylanilino)-1,3,5-triazin-2-yl]methyl ester | benzofurans | ||
3-chloro-1-(4-methoxyphenyl)-4-(3-methyl-1-piperidinyl)pyrrole-2,5-dione | maleimides | ||
2-[3-(2-chloro-6-fluorophenyl)-5-methyl-4-isoxazolyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazole | (trifluoromethyl)benzenes | ||
N-[2-furanyl-(8-hydroxy-7-quinolinyl)methyl]-2-methylpropanamide | hydroxyquinoline | ||
4-(1-methyl-3-indolyl)-N-propan-2-ylbutanamide | indoles | ||
1-(2,1,3-benzothiadiazol-4-ylsulfonyl)-N-(6-methyl-1,3-benzothiazol-2-yl)-3-piperidinecarboxamide | benzothiadiazole | ||
1-cyclopentyl-N-[2-(3,4-dihydro-1H-isoquinolin-2-yl)ethyl]-5-oxo-3-pyrrolidinecarboxamide | isoquinolines | ||
4-[2-(1-cyclohexenyl)ethyl]-1-cyclohexyl-3-pyridin-4-ylpiperazine-2,5-dione | piperazines; pyridines | ||
N-(3-acetylphenyl)-3,5-dimethyl-4-isoxazolesulfonamide | aromatic ketone | ||
N-[1-(cyclohexylamino)-2-methyl-1-oxobutan-2-yl]-N-(2-furanylmethyl)-2-pyridinecarboxamide | organonitrogen compound; organooxygen compound | ||
N-(2-methylphenyl)-1-phenazinecarboxamide | phenazines | ||
5-Nitroisatin | indoles | anticoronaviral agent | |
1-(3,4-dihydro-1H-isoquinolin-2-yl)-2-[[5-methyl-2-(4-methylphenyl)-4-oxazolyl]methylsulfonyl]ethanone | 1,3-oxazoles | ||
phenylalanyl-prolyl-arginine methyl chloride | phenylalanyl-prolyl-arginine methyl chloride: selective affinity label for thrombin; RN given refers to parent (L-Pro-D-Phe-(S))-isomer | ||
1-(3-methoxyphenyl)-3-[2-(methylthio)phenyl]urea | ureas | ||
5-Chloro-3-pyridinyl 2-furoate | carboxylic ester | anticoronaviral agent | |
rivaroxaban | rivaroxaban : A monocarboxylic acid amide obtained by formal condensation of the carboxy group of 5-chlorothiophene-2-carboxylic acid with the amino group of 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl}morpholin-3-one. An anticoagulant used for prophylaxis of venous thromboembolism in patients with knee or hip replacement surgery. Rivaroxaban: A morpholine and thiophene derivative that functions as a FACTOR XA INHIBITOR and is used in the treatment and prevention of DEEP-VEIN THROMBOSIS and PULMONARY EMBOLISM. It is also used for the prevention of STROKE and systemic embolization in patients with non-valvular ATRIAL FIBRILLATION, and for the prevention of atherothrombotic events in patients after an ACUTE CORONARY SYNDROME. | aromatic amide; lactam; monocarboxylic acid amide; morpholines; organochlorine compound; oxazolidinone; thiophenes | anticoagulant; EC 3.4.21.6 (coagulation factor Xa) inhibitor |
th 302 | TH 302: an hypoxia-activated prodrug of bromo-isophosphoramide mustard; an antineoplastic agent | ||
N-[4-(6-chloro-5-nitro-1H-benzimidazol-2-yl)phenyl]acetamide | benzimidazoles |