Target Information
| Target General Information | Top | |||||
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| Target ID |
T17758
(Former ID: TTDC00312)
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| Target Name |
Urokinase-type plasminogen activator (PLAU)
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| Synonyms |
UPA; U-plasminogen activator
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| Gene Name |
PLAU
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Inherited coagulation factor deficiency [ICD-11: 3B14] | |||||
| 2 | Myocardial infarction [ICD-11: BA41-BA43] | |||||
| Function |
Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.
Click to Show/Hide
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| BioChemical Class |
Peptidase
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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 Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| ADReCS ID | BADD_A01328 | |||||
| HIT2.0 ID | T84P70 | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 2 Approved Drugs | + | ||||
| 1 | Pro-urokinase | Drug Info | Approved | Thrombin deficiency | [2] | |
| 2 | Urokinase | Drug Info | Approved | Myocardial infarction | [3] | |
| Clinical Trial Drug(s) | [+] 6 Clinical Trial Drugs | + | ||||
| 1 | Amediplase | Drug Info | Phase 3 | Thrombosis | [3], [4] | |
| 2 | Saruplase | Drug Info | Phase 2 | Thrombosis | [5] | |
| 3 | Upamostat | Drug Info | Phase 2 | Breast cancer | [6], [7] | |
| 4 | HTU-PA | Drug Info | Phase 1/2 | Cerebrovascular ischaemia | [8] | |
| 5 | PMID18163548C4 | Drug Info | Clinical trial | Reperfusion injury | [9], [10] | |
| 6 | UK-356202 | Drug Info | Clinical trial | Myocardial hypertrophy | [11] | |
| Discontinued Drug(s) | [+] 2 Discontinued Drugs | + | ||||
| 1 | WX-UK1 | Drug Info | Discontinued in Phase 1/2 | Solid tumour/cancer | [12], [13] | |
| 2 | B-428 | Drug Info | Terminated | Solid tumour/cancer | [14] | |
| Mode of Action | [+] 3 Modes of Action | + | ||||
| Modulator | [+] 4 Modulator drugs | + | ||||
| 1 | Pro-urokinase | Drug Info | [1] | |||
| 2 | Urokinase | Drug Info | [15] | |||
| 3 | ATF-HI-8 | Drug Info | [30] | |||
| 4 | B-623 | Drug Info | [31] | |||
| Inhibitor | [+] 34 Inhibitor drugs | + | ||||
| 1 | PAI-1 | Drug Info | [16] | |||
| 2 | Upamostat | Drug Info | [7] | |||
| 3 | PMID18163548C4 | Drug Info | [9] | |||
| 4 | UK-356202 | Drug Info | [11] | |||
| 5 | PAI-2 | Drug Info | [18] | |||
| 6 | WX-UK1 | Drug Info | [19] | |||
| 7 | B-428 | Drug Info | [20] | |||
| 8 | (2R)-1-(2,6-dimethylphenoxy)propan-2-amine | Drug Info | [21] | |||
| 9 | (3,4-dichlorophenyl)(1H-pyrazol-1-yl)methanone | Drug Info | [22] | |||
| 10 | (3-nitro-1H-pyrazol-1-yl)(p-tolyl)methanone | Drug Info | [22] | |||
| 11 | (4-bromo-1H-pyrazol-1-yl)(p-tolyl)methanone | Drug Info | [22] | |||
| 12 | (4-guanidino-benzyl)-carbamic acid benzyl ester | Drug Info | [23] | |||
| 13 | (4-nitro-1H-pyrazol-1-yl)(o-tolyl)methanone | Drug Info | [22] | |||
| 14 | (4-nitro-1H-pyrazol-1-yl)(phenyl)methanone | Drug Info | [22] | |||
| 15 | 1-benzoyl-N-phenyl-1H-pyrazole-3-carboxamide | Drug Info | [22] | |||
| 16 | 1-guanidino-7-isoquinolinesulphonamide | Drug Info | [24] | |||
| 17 | 1-guanidino-N-phenyl-7-isoquinolinesulphonamide | Drug Info | [24] | |||
| 18 | 1-[4-(2-oxo-2-phenylethyl)phenyl]guanidine | Drug Info | [21] | |||
| 19 | 2-(2-Hydroxy-phenyl)-1H-indole-5-carboxamidine | Drug Info | [25] | |||
| 20 | 2-Amino-5-Hydroxy-Benzimidazole | Drug Info | [26] | |||
| 21 | 2-nas-phe(3-am)-4-(2-guanidinoethyl)piperidine | Drug Info | [27] | |||
| 22 | 4-chloro-1-guanidino-7-isoquinolinesulphonamide | Drug Info | [24] | |||
| 23 | 4-iodobenzo[b]thiophene 2-carboxamidine | Drug Info | [28], [29] | |||
| 24 | 4-methoxy-N'-(2-phenylacetyl)benzohydrazide | Drug Info | [22] | |||
| 25 | 5-Methylsulfanyl-thiophene-2-carboxamidine | Drug Info | [29] | |||
| 26 | 6-(N-Phenylcarbamyl)-2-Naphthalenecarboxamidine | Drug Info | [26] | |||
| 27 | Benzamidine | Drug Info | [26] | |||
| 28 | CRA_10655 | Drug Info | [21] | |||
| 29 | CRA_8696 | Drug Info | [21] | |||
| 30 | Fucose | Drug Info | [26] | |||
| 31 | N-(1-Adamantyl)-N'-(4-Guanidinobenzyl)Urea | Drug Info | [26] | |||
| 32 | Recombinant human pro-urokinase | Drug Info | [1] | |||
| 33 | Thieno[2,3-B]Pyridine-2-Carboxamidine | Drug Info | [21] | |||
| 34 | UPA-targeted oncolytic Sendai virus | Drug Info | [1] | |||
| Activator | [+] 4 Activator drugs | + | ||||
| 1 | Amediplase | Drug Info | [3] | |||
| 2 | Saruplase | Drug Info | [5] | |||
| 3 | HTU-PA | Drug Info | [17] | |||
| 4 | ATN-658 | Drug Info | [1] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target-regulating Transcription Factors | ||||||
| Target-interacting Proteins | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | URL: 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. (Target id: 2393). | |||||
| REF 2 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 3 | Emerging drugs in peripheral arterial disease. Expert Opin Emerg Drugs. 2006 Mar;11(1):75-90. | |||||
| REF 4 | Amediplase: CGP 42935, K2tu-PA, MEN 9036. BioDrugs. 2002;16(5):378-9. | |||||
| REF 5 | 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 6 | URL: 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 7 | 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 8 | ClinicalTrials.gov (NCT00418275) Safety Study of a Recombinant Human Plasminogen Activator to Treat Acute Ischemic Stroke.. U.S. National Institutes of Health. | |||||
| REF 9 | 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 10 | URL: 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 11 | Selective urokinase-type plasminogen activator (uPA) inhibitors. Part 3: 1-isoquinolinylguanidines. Bioorg Med Chem Lett. 2004 Jun 21;14(12):3227-30. | |||||
| REF 12 | URL: 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 13 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800012176) | |||||
| REF 14 | 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 15 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. | |||||
| REF 16 | 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. | |||||
| REF 17 | Characterization of the dexamethasone-induced inhibitor of plasminogen activator in HTC hepatoma cells. J Biol Chem. 1986 Mar 25;261(9):4352-7. | |||||
| REF 18 | Topological localization of plasminogen activator inhibitor type 2. Cytometry. 2000 May 1;40(1):32-41. | |||||
| REF 19 | 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 20 | Natural and synthetic inhibitors of the tumor-associated serine protease urokinase-type plasminogen activator. Adv Exp Med Biol. 2000;477:331-41. | |||||
| REF 21 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
| REF 22 | N-benzoylpyrazoles are novel small-molecule inhibitors of human neutrophil elastase. J Med Chem. 2007 Oct 4;50(20):4928-38. | |||||
| REF 23 | Small, potent, and selective diaryl phosphonate inhibitors for urokinase-type plasminogen activator with in vivo antimetastatic properties. J Med Chem. 2007 Dec 27;50(26):6638-46. | |||||
| REF 24 | Selective urokinase-type plasminogen activator inhibitors. 4. 1-(7-sulfonamidoisoquinolinyl)guanidines. J Med Chem. 2007 May 17;50(10):2341-51. | |||||
| REF 25 | Development of serine protease inhibitors displaying a multicentered short (<2.3 A) hydrogen bond binding mode: inhibitors of urokinase-type plasmi... J Med Chem. 2001 Aug 16;44(17):2753-71. | |||||
| REF 26 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 27 | Secondary amides of sulfonylated 3-amidinophenylalanine. New potent and selective inhibitors of matriptase. J Med Chem. 2006 Jul 13;49(14):4116-26. | |||||
| REF 28 | 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 29 | Design and synthesis of 4,5-disubstituted-thiophene-2-amidines as potent urokinase inhibitors. Bioorg Med Chem Lett. 2002 Feb 11;12(3):491-5. | |||||
| REF 30 | Inhibitory effect of a conjugate between human urokinase and urinary trypsin inhibitor on tumor cell invasion in vitro. J Biol Chem. 1995 Apr 7;270(14):8361-6. | |||||
| REF 31 | Angiostatic activity of synthetic inhibitors of urokinase type plasminogen activator. Oncol Rep. 1999 May-Jun;6(3):523-6. | |||||
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