Target Information
Target General Infomation | |||||
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Target ID |
T17758
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Former ID |
TTDC00312
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Target Name |
Urokinase-type plasminogen activator
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Gene Name |
PLAU
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Synonyms |
U-plasminogen activator; UPA; PLAU
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Target Type |
Successful
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Disease | Breast cancer [ICD9: 174, 175; ICD10: C50] | ||||
Cerebrovascular ischaemia [ICD9: 434.91; ICD10: I61-I63] | |||||
Cancer [ICD9: 140-229; ICD10: C00-C96] | |||||
Deep venous thrombosis; Pulmonary embolism; Myocardial infarction [ICD9: 410, 415.1, 437.6, 444.9, 453, 453.40, 671.5, 671.9; ICD10: I21, I22, I26, I74, I80-I82, I80.2, I82, O88, T79.0-T79.1] | |||||
Myocardial infarction; Thrombolysis [ICD9:410, 415.1, 434.91, 459.9; ICD10: I21, I22, I21-I22, I26, I61-I63, I99.9] | |||||
Myocardial infarction [ICD9: 410; ICD10: I21, I22] | |||||
Myocardial ischemia; Reperfusion injury [ICD9: 459.89; ICD10: I99.8] | |||||
Myocardial hypertrophy [ICD10: I51.7] | |||||
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48] | |||||
Thromboembolism [ICD9: 437.6, 453, 671.5, 671.9; ICD10: I80-I82] | |||||
Thrombin deficiency [ICD9: 437.6, 444.9, 453, 671.5, 671.9; ICD10: I74, I80-I82, I82, O88, T79.0-T79.1] | |||||
Unspecified [ICD code not available] | |||||
Function |
Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.
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BioChemical Class |
Peptidase
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Target Validation |
T17758
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UniProt ID | |||||
EC Number |
EC 3.4.21.73
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Sequence |
MRALLARLLLCVLVVSDSKGSNELHQVPSNCDCLNGGTCVSNKYFSNIHWCNCPKKFGGQ
HCEIDKSKTCYEGNGHFYRGKASTDTMGRPCLPWNSATVLQQTYHAHRSDALQLGLGKHN YCRNPDNRRRPWCYVQVGLKPLVQECMVHDCADGKKPSSPPEELKFQCGQKTLRPRFKII GGEFTTIENQPWFAAIYRRHRGGSVTYVCGGSLISPCWVISATHCFIDYPKKEDYIVYLG RSRLNSNTQGEMKFEVENLILHKDYSADTLAHHNDIALLKIRSKEGRCAQPSRTIQTICL PSMYNDPQFGTSCEITGFGKENSTDYLYPEQLKMTVVKLISHRECQQPHYYGSEVTTKML CAADPQWKTDSCQGDSGGPLVCSLQGRMTLTGIVSWGRGCALKDKPGVYTRVSHFLPWIR SHTKEENGLAL |
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Drugs and Mode of Action | |||||
Drug(s) | Pro-urokinase | Drug Info | Approved | Thrombin deficiency | [551871] |
Urokinase | Drug Info | Approved | Deep venous thrombosis; Pulmonary embolism; Myocardial infarction | [536186] | |
PAI-1 | Drug Info | Phase 4 | Discovery agent | [522460] | |
Amediplase | Drug Info | Phase 3 | Myocardial infarction; Thrombolysis | [526449], [536186] | |
Saruplase | Drug Info | Phase 2 | Thromboembolism | [533625] | |
Upamostat | Drug Info | Phase 2 | Breast cancer | [532234], [541632] | |
HTU-PA | Drug Info | Phase 1/2 | Cerebrovascular ischaemia | [521944] | |
compound 4 | Drug Info | Clinical trial | Myocardial ischemia; Reperfusion injury | [525421], [541671] | |
UK-356202 | Drug Info | Clinical trial | Myocardial hypertrophy | [527081] | |
PAI-2 | Drug Info | Discontinued in Phase 2 | Discovery agent | [545764] | |
WX-UK1 | Drug Info | Discontinued in Phase 1/2 | Solid tumours | [541633], [547024] | |
B-428 | Drug Info | Terminated | Cancer | [546589] | |
Inhibitor | (2R)-1-(2,6-dimethylphenoxy)propan-2-amine | Drug Info | [551374] | ||
(3,4-dichlorophenyl)(1H-pyrazol-1-yl)methanone | Drug Info | [529037] | |||
(3-nitro-1H-pyrazol-1-yl)(p-tolyl)methanone | Drug Info | [529037] | |||
(4-bromo-1H-pyrazol-1-yl)(p-tolyl)methanone | Drug Info | [529037] | |||
(4-guanidino-benzyl)-carbamic acid benzyl ester | Drug Info | [529189] | |||
(4-nitro-1H-pyrazol-1-yl)(o-tolyl)methanone | Drug Info | [529037] | |||
(4-nitro-1H-pyrazol-1-yl)(phenyl)methanone | Drug Info | [529037] | |||
1-benzoyl-N-phenyl-1H-pyrazole-3-carboxamide | Drug Info | [529037] | |||
1-guanidino-7-isoquinolinesulphonamide | Drug Info | [528796] | |||
1-guanidino-N-phenyl-7-isoquinolinesulphonamide | Drug Info | [528796] | |||
1-[4-(2-oxo-2-phenylethyl)phenyl]guanidine | Drug Info | [551374] | |||
2-(2-Hydroxy-phenyl)-1H-indole-5-carboxamidine | Drug Info | [526118] | |||
2-amidino-4-iodobenzothiophene | Drug Info | [526259] | |||
2-Amino-5-Hydroxy-Benzimidazole | Drug Info | [551393] | |||
2-nas-phe(3-am)-4-(2-guanidinoethyl)piperidine | Drug Info | [528292] | |||
4-chloro-1-guanidino-7-isoquinolinesulphonamide | Drug Info | [528796] | |||
4-iodobenzo[b]thiophene 2-carboxamidine | Drug Info | [534982] | |||
4-Iodobenzo[B]Thiophene-2-Carboxamidine | Drug Info | [551374] | |||
4-methoxy-N'-(2-phenylacetyl)benzohydrazide | Drug Info | [529037] | |||
5-Methylsulfanyl-thiophene-2-carboxamidine | Drug Info | [526259] | |||
6-(N-Phenylcarbamyl)-2-Naphthalenecarboxamidine | Drug Info | [551393] | |||
B-428 | Drug Info | [525788] | |||
Benzamidine | Drug Info | [551393] | |||
compound 4 | Drug Info | [525421] | |||
CRA_10655 | Drug Info | [551374] | |||
CRA_8696 | Drug Info | [551374] | |||
Fucose | Drug Info | [551393] | |||
N-(1-Adamantyl)-N'-(4-Guanidinobenzyl)Urea | Drug Info | [551393] | |||
PAI-1 | Drug Info | [537833] | |||
PAI-2 | Drug Info | [534979] | |||
Recombinant human pro-urokinase | Drug Info | [543617] | |||
Thieno[2,3-B]Pyridine-2-Carboxamidine | Drug Info | [551374] | |||
UK-356202 | Drug Info | [527081] | |||
UPA-targeted oncolytic Sendai virus | Drug Info | [543617] | |||
Upamostat | Drug Info | [532234] | |||
WX-UK1 | Drug Info | [527095] | |||
Activator | Amediplase | Drug Info | [536186] | ||
ATN-658 | Drug Info | [543617] | |||
HTU-PA | Drug Info | [533388] | |||
Saruplase | Drug Info | [533625] | |||
Modulator | ATF-HI-8 | Drug Info | |||
B-623 | Drug Info | ||||
Pro-urokinase | Drug Info | [543617] | |||
Urokinase | Drug Info | [556264] | |||
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
TEP | EXP Info | ||||
Pathways | |||||
KEGG Pathway | NF-kappa B signaling pathway | ||||
Complement and coagulation cascades | |||||
Transcriptional misregulation in cancer | |||||
Proteoglycans in cancer | |||||
MicroRNAs in cancer | |||||
NetPath Pathway | IL2 Signaling Pathway | ||||
EGFR1 Signaling Pathway | |||||
PANTHER Pathway | Blood coagulation | ||||
Plasminogen activating cascade | |||||
CCKR signaling map ST | |||||
Pathway Interaction Database | Beta1 integrin cell surface interactions | ||||
E2F transcription factor network | |||||
Beta3 integrin cell surface interactions | |||||
Osteopontin-mediated events | |||||
Validated transcriptional targets of AP1 family members Fra1 and Fra2 | |||||
amb2 Integrin signaling | |||||
ATF-2 transcription factor network | |||||
AP-1 transcription factor network | |||||
Beta2 integrin cell surface interactions | |||||
Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling | |||||
Beta5 beta6 beta7 and beta8 integrin cell surface interactions | |||||
FGF signaling pathway | |||||
Reactome | Dissolution of Fibrin Clot | ||||
WikiPathways | DNA Damage Response (only ATM dependent) | ||||
Senescence and Autophagy in Cancer | |||||
Complement and Coagulation Cascades | |||||
Endochondral Ossification | |||||
Wnt Signaling Pathway | |||||
Wnt Signaling Pathway and Pluripotency | |||||
Blood Clotting Cascade | |||||
Dissolution of Fibrin Clot | |||||
Osteopontin Signaling | |||||
References | |||||
Ref 521944 | ClinicalTrials.gov (NCT00418275) Safety Study of a Recombinant Human Plasminogen Activator to Treat Acute Ischemic Stroke.. U.S. National Institutes of Health. | ||||
Ref 522460 | ClinicalTrials.gov (NCT00770328) The Effects of Pentoxifylline on PAI-1 in an Obese Population. U.S. National Institutes of Health. | ||||
Ref 525421 | Fragment-based discovery of mexiletine derivatives as orally bioavailable inhibitors of urokinase-type plasminogen activator. J Med Chem. 2008 Jan 24;51(2):183-6. | ||||
Ref 527081 | Bioorg Med Chem Lett. 2004 Jun 21;14(12):3227-30.Selective urokinase-type plasminogen activator (uPA) inhibitors. Part 3: 1-isoquinolinylguanidines. | ||||
Ref 532234 | Phase II randomised proof-of-concept study of the urokinase inhibitor upamostat (WX-671) in combination with gemcitabine compared with gemcitabine alone in patients with non-resectable, locally advanced pancreatic cancer. Br J Cancer. 2013 Mar 5;108(4):766-70. | ||||
Ref 533625 | Pharmacokinetics and pharmacodynamics of saruplase, an unglycosylated single-chain urokinase-type plasminogen activator, in patients with acute myocardial infarction. Thromb Haemost. 1994 Nov;72(5):740-4. | ||||
Ref 536186 | Emerging drugs in peripheral arterial disease. Expert Opin Emerg Drugs. 2006 Mar;11(1):75-90. | ||||
Ref 541632 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6497). | ||||
Ref 541633 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6498). | ||||
Ref 541671 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6545). | ||||
Ref 545764 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004611) | ||||
Ref 546589 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009078) | ||||
Ref 525421 | Fragment-based discovery of mexiletine derivatives as orally bioavailable inhibitors of urokinase-type plasminogen activator. J Med Chem. 2008 Jan 24;51(2):183-6. | ||||
Ref 525788 | Natural and synthetic inhibitors of the tumor-associated serine protease urokinase-type plasminogen activator. Adv Exp Med Biol. 2000;477:331-41. | ||||
Ref 526118 | J Med Chem. 2001 Aug 16;44(17):2753-71.Development of serine protease inhibitors displaying a multicentered short (<2.3 A) hydrogen bond binding mode: inhibitors of urokinase-type plasminogen activator and factor Xa. | ||||
Ref 526259 | Bioorg Med Chem Lett. 2002 Feb 11;12(3):491-5.Design and synthesis of 4,5-disubstituted-thiophene-2-amidines as potent urokinase inhibitors. | ||||
Ref 527081 | Bioorg Med Chem Lett. 2004 Jun 21;14(12):3227-30.Selective urokinase-type plasminogen activator (uPA) inhibitors. Part 3: 1-isoquinolinylguanidines. | ||||
Ref 527095 | Inhibition of the invasion capacity of carcinoma cells by WX-UK1, a novel synthetic inhibitor of the urokinase-type plasminogen activator system. Int J Cancer. 2004 Jul 20;110(6):815-24. | ||||
Ref 528292 | J Med Chem. 2006 Jul 13;49(14):4116-26.Secondary amides of sulfonylated 3-amidinophenylalanine. New potent and selective inhibitors of matriptase. | ||||
Ref 528796 | J Med Chem. 2007 May 17;50(10):2341-51. Epub 2007 Apr 21.Selective urokinase-type plasminogen activator inhibitors. 4. 1-(7-sulfonamidoisoquinolinyl)guanidines. | ||||
Ref 529037 | J Med Chem. 2007 Oct 4;50(20):4928-38. Epub 2007 Sep 12.N-benzoylpyrazoles are novel small-molecule inhibitors of human neutrophil elastase. | ||||
Ref 529189 | J Med Chem. 2007 Dec 27;50(26):6638-46. Epub 2007 Dec 1.Small, potent, and selective diaryl phosphonate inhibitors for urokinase-type plasminogen activator with in vivo antimetastatic properties. | ||||
Ref 532234 | Phase II randomised proof-of-concept study of the urokinase inhibitor upamostat (WX-671) in combination with gemcitabine compared with gemcitabine alone in patients with non-resectable, locally advanced pancreatic cancer. Br J Cancer. 2013 Mar 5;108(4):766-70. | ||||
Ref 533388 | Characterization of the dexamethasone-induced inhibitor of plasminogen activator in HTC hepatoma cells. J Biol Chem. 1986 Mar 25;261(9):4352-7. | ||||
Ref 533625 | Pharmacokinetics and pharmacodynamics of saruplase, an unglycosylated single-chain urokinase-type plasminogen activator, in patients with acute myocardial infarction. Thromb Haemost. 1994 Nov;72(5):740-4. | ||||
Ref 534979 | Topological localization of plasminogen activator inhibitor type 2. Cytometry. 2000 May 1;40(1):32-41. | ||||
Ref 534982 | Structural basis for selectivity of a small molecule, S1-binding, submicromolar inhibitor of urokinase-type plasminogen activator. Chem Biol. 2000 Apr;7(4):299-312. | ||||
Ref 536186 | Emerging drugs in peripheral arterial disease. Expert Opin Emerg Drugs. 2006 Mar;11(1):75-90. | ||||
Ref 537833 | Urokinase-type plasminogen activator and its inhibitor PAI-1: predictors of poor response to tamoxifen therapy in recurrent breast cancer. J Natl Cancer Inst. 1995 May 17;87(10):751-6. |
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