Proteins > Tissue-type plasminogen activator
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Tissue-type plasminogen activator
A tissue-type plasminogen activator that is encoded in the genome of human. [PRO:DNx, UniProtKB:P00750]
Synonyms
t-PA;
t-plasminogen activator;
tPA;
EC 3.4.21.68
Research
Bioassay Publications (33)
| Timeframe | Studies on this Protein(%) | All Drugs % |
|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 5 (15.15) | 18.2507 |
| 2000's | 19 (57.58) | 29.6817 |
| 2010's | 8 (24.24) | 24.3611 |
| 2020's | 1 (3.03) | 2.80 |
Compounds (31)
Drugs with Inhibition Measurements
Drugs with Other Measurements
| Drug | Taxonomy | Measurement | Average (mM) | Bioassay(s) | Publication(s) |
|---|
| dpc 423 | Homo sapiens (human) | Activity | 45,000.0000 | 1 | 1 |
6-Substituted amiloride derivatives as inhibitors of the urokinase-type plasminogen activator for use in metastatic disease.Bioorganic & medicinal chemistry letters, , 12-15, Volume: 29, Issue:24, 2019
2-Amidino analogs of glycine-amiloride conjugates: inhibitors of urokinase-type plasminogen activator.Bioorganic & medicinal chemistry letters, , Apr-01, Volume: 22, Issue:7, 2012
Development of irreversible diphenyl phosphonate inhibitors for urokinase plasminogen activator.Journal of medicinal chemistry, , May-06, Volume: 47, Issue:10, 2004
Crystals of the urokinase type plasminogen activator variant beta(c)-uPAin complex with small molecule inhibitors open the way towards structure-based drug design.Journal of molecular biology, , Aug-11, Volume: 301, Issue:2, 2000
Discovery of N-[(1R,2S,5S)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-5-(dimethylcarbamoyl)cyclohexyl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide hydrochloride: a novel, potent and orally active direct inhibitor of factor Xa.Bioorganic & medicinal chemistry, , Feb-01, Volume: 17, Issue:3, 2009
Retro-binding thrombin active site inhibitors: identification of an orally active inhibitor of thrombin catalytic activity.Bioorganic & medicinal chemistry letters, , Nov-04, Volume: 12, Issue:21, 2002
Structure-activity study of tripeptide thrombin inhibitors using alpha-alkyl amino acids and other conformationally constrained amino acid substitutions.Journal of medicinal chemistry, , Oct-27, Volume: 38, Issue:22, 1995
Fibrinolysis Inhibitors: Potential Drugs for the Treatment and Prevention of Bleeding.Journal of medicinal chemistry, , 02-27, Volume: 63, Issue:4, 2020
Antithrombotic effects of LB30870, a potent, orally active, selective and direct thrombin inhibitor, and pharmacokinetics of its prodrug.Bioorganic & medicinal chemistry letters, , Sep-01, Volume: 23, Issue:17, 2013
Identification of novel binding interactions in the development of potent, selective 2-naphthamidine inhibitors of urokinase. Synthesis, structural analysis, and SAR of N-phenyl amide 6-substitution.Journal of medicinal chemistry, , Jan-15, Volume: 47, Issue:2, 2004
Interaction with the S1 beta-pocket of urokinase: 8-heterocycle substituted and 6,8-disubstituted 2-naphthamidine urokinase inhibitors.Bioorganic & medicinal chemistry letters, , Jun-21, Volume: 14, Issue:12, 2004
Structure-activity relationship and pharmacokinetic profile of 5-ketopyrazole factor Xa inhibitors.Bioorganic & medicinal chemistry letters, , Jan-15, Volume: 18, Issue:2, 2008
Discovery of potent, efficacious, and orally bioavailable inhibitors of blood coagulation factor Xa with neutral P1 moieties.Bioorganic & medicinal chemistry letters, , Nov-01, Volume: 16, Issue:21, 2006
1-[3-Aminobenzisoxazol-5'-yl]-3-trifluoromethyl-6-[2'-(3-(R)-hydroxy-N-pyrrolidinyl)methyl-[1,1']-biphen-4-yl]-1,4,5,6-tetrahydropyrazolo-[3,4-c]-pyridin-7-one (BMS-740808) a highly potent, selective, efficacious, and orally bioavailable inhibitor of blooBioorganic & medicinal chemistry letters, , Aug-01, Volume: 16, Issue:15, 2006
Aminobenzisoxazoles with biaryl P4 moieties as potent, selective, and orally bioavailable factor Xa inhibitors.Bioorganic & medicinal chemistry letters, , Apr-01, Volume: 16, Issue:7, 2006
Dissecting and designing inhibitor selectivity determinants at the S1 site using an artificial Ala190 protease (Ala190 uPA).Journal of molecular biology, , Nov-19, Volume: 344, Issue:2, 2004
Crystals of the urokinase type plasminogen activator variant beta(c)-uPAin complex with small molecule inhibitors open the way towards structure-based drug design.Journal of molecular biology, , Aug-11, Volume: 301, Issue:2, 2000
Structural basis for selectivity of a small molecule, S1-binding, submicromolar inhibitor of urokinase-type plasminogen activator.Chemistry & biology, , Volume: 7, Issue:4, 2000
1-[3-Aminobenzisoxazol-5'-yl]-3-trifluoromethyl-6-[2'-(3-(R)-hydroxy-N-pyrrolidinyl)methyl-[1,1']-biphen-4-yl]-1,4,5,6-tetrahydropyrazolo-[3,4-c]-pyridin-7-one (BMS-740808) a highly potent, selective, efficacious, and orally bioavailable inhibitor of blooBioorganic & medicinal chemistry letters, , Aug-01, Volume: 16, Issue:15, 2006
Discovery of betrixaban (PRT054021), N-(5-chloropyridin-2-yl)-2-(4-(N,N-dimethylcarbamimidoyl)benzamido)-5-methoxybenzamide, a highly potent, selective, and orally efficacious factor Xa inhibitor.Bioorganic & medicinal chemistry letters, , Apr-15, Volume: 19, Issue:8, 2009
Enables
This protein enables 4 target(s):
| Target | Category | Definition |
|---|
| serine-type endopeptidase activity | molecular function | Catalysis of the hydrolysis of internal, alpha-peptide bonds in a polypeptide chain by a catalytic mechanism that involves a catalytic triad consisting of a serine nucleophile that is activated by a proton relay involving an acidic residue (e.g. aspartate or glutamate) and a basic residue (usually histidine). [GOC:mah, https://www.ebi.ac.uk/merops/about/glossary.shtml#CATTYPE] |
| signaling receptor binding | molecular function | Binding to one or more specific sites on a receptor molecule, a macromolecule that undergoes combination with a hormone, neurotransmitter, drug or intracellular messenger to initiate a change in cell function. [GOC:bf, GOC:ceb, ISBN:0198506732] |
| protein binding | molecular function | Binding to a protein. [GOC:go_curators] |
| phosphoprotein binding | molecular function | Binding to a phosphorylated protein. [GOC:ai] |
Located In
This protein is located in 8 target(s):
| Target | Category | Definition |
|---|
| extracellular region | cellular component | The space external to the outermost structure of a cell. For cells without external protective or external encapsulating structures this refers to space outside of the plasma membrane. This term covers the host cell environment outside an intracellular parasite. [GOC:go_curators] |
| cytoplasm | cellular component | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. [ISBN:0198547684] |
| cell surface | cellular component | The external part of the cell wall and/or plasma membrane. [GOC:jl, GOC:mtg_sensu, GOC:sm] |
| secretory granule | cellular component | A small subcellular vesicle, surrounded by a membrane, that is formed from the Golgi apparatus and contains a highly concentrated protein destined for secretion. Secretory granules move towards the periphery of the cell and upon stimulation, their membranes fuse with the cell membrane, and their protein load is exteriorized. Processing of the contained protein may take place in secretory granules. [GOC:mah, ISBN:0198506732] |
| apical part of cell | cellular component | The region of a polarized cell that forms a tip or is distal to a base. For example, in a polarized epithelial cell, the apical region has an exposed surface and lies opposite to the basal lamina that separates the epithelium from other tissue. [GOC:mah, ISBN:0815316194] |
| extracellular exosome | cellular component | A vesicle that is released into the extracellular region by fusion of the limiting endosomal membrane of a multivesicular body with the plasma membrane. Extracellular exosomes, also simply called exosomes, have a diameter of about 40-100 nm. [GOC:BHF, GOC:mah, GOC:vesicles, PMID:15908444, PMID:17641064, PMID:19442504, PMID:19498381, PMID:22418571, PMID:24009894] |
| Schaffer collateral - CA1 synapse | cellular component | A synapse between the Schaffer collateral axon of a CA3 pyramidal cell and a CA1 pyramidal cell. [PMID:16399689] |
| glutamatergic synapse | cellular component | A synapse that uses glutamate as a neurotransmitter. [GOC:dos] |
Active In
This protein is active in 1 target(s):
| Target | Category | Definition |
|---|
| extracellular space | cellular component | That part of a multicellular organism outside the cells proper, usually taken to be outside the plasma membranes, and occupied by fluid. [ISBN:0198547684] |
Part Of
This protein is part of 1 target(s):
| Target | Category | Definition |
|---|
| serine protease inhibitor complex | cellular component | A heterodimeric protein complex that contains a serine protease inhibitor and a protease; formation of the complex inhibits serine protease activity. [GOC:ans, PMID:6323392] |
Involved In
This protein is involved in 13 target(s):
| Target | Category | Definition |
|---|
| response to hypoxia | biological process | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating lowered oxygen tension. Hypoxia, defined as a decline in O2 levels below normoxic levels of 20.8 - 20.95%, results in metabolic adaptation at both the cellular and organismal level. [GOC:hjd] |
| proteolysis | biological process | The hydrolysis of proteins into smaller polypeptides and/or amino acids by cleavage of their peptide bonds. [GOC:bf, GOC:mah] |
| blood coagulation | biological process | The sequential process in which the multiple coagulation factors of the blood interact, ultimately resulting in the formation of an insoluble fibrin clot; it may be divided into three stages: stage 1, the formation of intrinsic and extrinsic prothrombin converting principle; stage 2, the formation of thrombin; stage 3, the formation of stable fibrin polymers. [PMID:30700128] |
| negative regulation of plasminogen activation | biological process | Any process that decreases 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] |
| plasminogen activation | biological process | The process in which inactive plasminogen is processed to active plasmin. This process includes cleavage at an internal Arg-Val site to form an N-terminal A-chain and C-terminal B-chain held together by a disulfide bond, and can include further proteolytic cleavage events to remove the preactivation peptide. [PMID:9548733] |
| protein modification process | biological process | The covalent alteration of one or more amino acids occurring in proteins, peptides and nascent polypeptides (co-translational, post-translational modifications). Includes the modification of charged tRNAs that are destined to occur in a protein (pre-translation modification). [GOC:bf, GOC:jl] |
| fibrinolysis | biological process | A process that solubilizes fibrin in the bloodstream of a multicellular organism, chiefly by the proteolytic action of plasmin. [GOC:jl, PMID:15842654] |
| negative regulation of proteolysis | biological process | Any process that stops, prevents, or reduces the frequency, rate or extent of the hydrolysis of a peptide bond or bonds within a protein. [GOC:go_curators] |
| negative regulation of fibrinolysis | biological process | Any process that stops, prevents, or reduces the frequency, rate or extent of fibrinolysis, an ongoing process that solubilizes fibrin, resulting in the removal of small blood clots. [GOC:ai] |
| prevention of polyspermy | biological process | The negative regulation of fertilization process that takes place as part of egg activation, ensuring that only a single sperm fertilizes the egg. [GOC:dph] |
| trans-synaptic signaling by BDNF, modulating synaptic transmission | biological process | Cell-cell signaling between presynapse and postsynapse, via the vesicular release and reception of brain derived neurotrophic factor (BDNF), that modulates the synaptic transmission properties of the synapse. [GOC:dos] |
| platelet-derived growth factor receptor signaling pathway | biological process | The series of molecular signals initiated by a ligand binding to a platelet-derived growth factor receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. [GOC:ceb] |
| smooth muscle cell migration | biological process | The orderly movement of a smooth muscle cell from one site to another, often during the development of a multicellular organism. [CL:0000192, GOC:mtg_muscle] |