Target Information
| Target General Information | Top | |||||
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| Target ID |
T89034
(Former ID: TTDS00392)
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| Target Name |
Plasminogen (PLG)
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| Synonyms |
Plasmin
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| Gene Name |
PLG
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 6 Target-related Diseases | + | ||||
| 1 | Angina pectoris [ICD-11: BA40] | |||||
| 2 | Bleeding disorder [ICD-11: GA20-GA21] | |||||
| 3 | Menopausal disorder [ICD-11: GA30] | |||||
| 4 | Myocardial infarction [ICD-11: BA41-BA43] | |||||
| 5 | Procedure injury [ICD-11: NE81] | |||||
| 6 | Pulmonary thromboembolism [ICD-11: BB00] | |||||
| Function |
In ovulation, weakens the walls of the Graafian follicle. It activates the urokinase-type plasminogen activator, collagenases and several complement zymogens, such as C1 and C5. Cleavage of fibronectin and laminin leads to cell detachment and apoptosis. Also cleaves fibrin, thrombospondin and von Willebrand factor. Its role in tissue remodeling and tumor invasion may be modulated by CSPG4. Binds to cells. Plasmin dissolves the fibrin of blood clots and acts as a proteolytic factor in a variety of other processes including embryonic development, tissue remodeling, tumor invasion, and inflammation.
Click to Show/Hide
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| BioChemical Class |
Peptidase
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| UniProt ID | ||||||
| EC Number |
EC 3.4.21.7
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| Sequence |
MEHKEVVLLLLLFLKSGQGEPLDDYVNTQGASLFSVTKKQLGAGSIEECAAKCEEDEEFT
CRAFQYHSKEQQCVIMAENRKSSIIIRMRDVVLFEKKVYLSECKTGNGKNYRGTMSKTKN GITCQKWSSTSPHRPRFSPATHPSEGLEENYCRNPDNDPQGPWCYTTDPEKRYDYCDILE CEEECMHCSGENYDGKISKTMSGLECQAWDSQSPHAHGYIPSKFPNKNLKKNYCRNPDRE LRPWCFTTDPNKRWELCDIPRCTTPPPSSGPTYQCLKGTGENYRGNVAVTVSGHTCQHWS AQTPHTHNRTPENFPCKNLDENYCRNPDGKRAPWCHTTNSQVRWEYCKIPSCDSSPVSTE QLAPTAPPELTPVVQDCYHGDGQSYRGTSSTTTTGKKCQSWSSMTPHRHQKTPENYPNAG LTMNYCRNPDADKGPWCFTTDPSVRWEYCNLKKCSGTEASVVAPPPVVLLPDVETPSEED CMFGNGKGYRGKRATTVTGTPCQDWAAQEPHRHSIFTPETNPRAGLEKNYCRNPDGDVGG PWCYTTNPRKLYDYCDVPQCAAPSFDCGKPQVEPKKCPGRVVGGCVAHPHSWPWQVSLRT RFGMHFCGGTLISPEWVLTAAHCLEKSPRPSSYKVILGAHQEVNLEPHVQEIEVSRLFLE PTRKDIALLKLSSPAVITDKVIPACLPSPNYVVADRTECFITGWGETQGTFGAGLLKEAQ LPVIENKVCNRYEFLNGRVQSTELCAGHLAGGTDSCQGDSGGPLVCFEKDKYILQGVTSW GLGCARPNKPGVYVRVSRFVTWIEGVMRNN Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T14JSX | |||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 8 Approved Drugs | + | ||||
| 1 | Alteplase | Drug Info | Approved | Pulmonary embolism | [2] | |
| 2 | Aminocaproic Acid | Drug Info | Approved | Bleeding disorder | [3] | |
| 3 | Anistreplase | Drug Info | Approved | Acute coronary syndrome | [4], [5] | |
| 4 | Ranolazine | Drug Info | Approved | Chronic/stable angina | [6], [7], [8] | |
| 5 | Reteplase | Drug Info | Approved | Heart attack | [5], [9] | |
| 6 | Streptokinase | Drug Info | Approved | Pulmonary embolism | [10] | |
| 7 | Tenecteplase | Drug Info | Approved | Myocardial infarction | [11] | |
| 8 | Tranexamic Acid | Drug Info | Approved | Excessive bleeding | [12], [13] | |
| Clinical Trial Drug(s) | [+] 5 Clinical Trial Drugs | + | ||||
| 1 | Desmoteplase | Drug Info | Phase 3 | Ischemic stroke | [14] | |
| 2 | Plasminogen | Drug Info | Phase 2/3 | Alzheimer disease | [15] | |
| 3 | RetinoStat | Drug Info | Phase 2 | Macular degeneration | [16] | |
| 4 | Troplasminogen alfa | Drug Info | Phase 2 | Myocardial infarction | [17] | |
| 5 | bis-triazole derivative 10 | Drug Info | Clinical trial | Otitis media | [18] | |
| Mode of Action | [+] 3 Modes of Action | + | ||||
| Activator | [+] 7 Activator drugs | + | ||||
| 1 | Alteplase | Drug Info | [19] | |||
| 2 | Anistreplase | Drug Info | [22], [23] | |||
| 3 | Reteplase | Drug Info | [25], [26] | |||
| 4 | Streptokinase | Drug Info | [27] | |||
| 5 | Tenecteplase | Drug Info | [19] | |||
| 6 | Desmoteplase | Drug Info | [28] | |||
| 7 | M5 | Drug Info | [24] | |||
| Inhibitor | [+] 14 Inhibitor drugs | + | ||||
| 1 | Aminocaproic Acid | Drug Info | [20], [21] | |||
| 2 | Tranexamic Acid | Drug Info | [1] | |||
| 3 | MELAGATRAN | Drug Info | [29] | |||
| 4 | bis-triazole derivative 10 | Drug Info | [32] | |||
| 5 | 1-(2-Oxo-2-p-tolyl-ethyl)-1H-indole-2,3-dione | Drug Info | [33] | |||
| 6 | 1-(3,3-Dimethyl-2-oxo-butyl)-1H-indole-2,3-dione | Drug Info | [33] | |||
| 7 | 1-guanidino-7-isoquinolinesulphonamide | Drug Info | [34] | |||
| 8 | 1-guanidino-N-phenyl-7-isoquinolinesulphonamide | Drug Info | [34] | |||
| 9 | 2-(2-Hydroxy-phenyl)-1H-indole-5-carboxamidine | Drug Info | [35] | |||
| 10 | Bicine | Drug Info | [36] | |||
| 11 | Grassystatin a | Drug Info | [37] | |||
| 12 | N-(4-Chloro-7-p-tolyl-isoquinolin-1-yl)-guanidine | Drug Info | [38] | |||
| 13 | Textilinin | Drug Info | [24] | |||
| 14 | XP-21510 | Drug Info | [24] | |||
| Modulator | [+] 5 Modulator drugs | + | ||||
| 1 | Ranolazine | Drug Info | [24] | |||
| 2 | Plasminogen | Drug Info | [24], [30] | |||
| 3 | RetinoStat | Drug Info | [16] | |||
| 4 | Troplasminogen alfa | Drug Info | [24], [31] | |||
| 5 | SMTP-0 | Drug Info | [24] | |||
| 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 | |||||
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| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| 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 | |||||
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| REF 1 | Evaluation of aprotinin and tranexamic acid in different in vitro and in vivo models of fibrinolysis, coagulation and thrombus formation. J Thromb Haemost. 2007 Oct;5(10):2113-8. | |||||
| REF 2 | Emerging drugs in peripheral arterial disease. Expert Opin Emerg Drugs. 2006 Mar;11(1):75-90. | |||||
| REF 3 | The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954. | |||||
| REF 4 | Acylated plasminogen-streptokinase activator complex: a new approach to thrombolytic therapy. Pharmacotherapy. 1990;10(2):115-26. | |||||
| REF 5 | Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. | |||||
| 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: 7291). | |||||
| REF 7 | 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101. | |||||
| REF 8 | Late sodium current in the pathophysiology of cardiovascular disease: consequences of sodium-calcium overload. Heart. 2006 Jul;92 Suppl 4:iv1-iv5. | |||||
| REF 9 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 10 | Emerging drugs for chemotherapy-induced mucositis. Expert Opin Emerg Drugs. 2008 Sep;13(3):511-22. | |||||
| REF 11 | Fibrinolytic agents for the management of ST-segment elevation myocardial infarction. Pharmacotherapy. 2007 Nov;27(11):1558-70. | |||||
| 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: 6573). | |||||
| REF 13 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 019281. | |||||
| REF 14 | ClinicalTrials.gov (NCT00111852) Study of Desmoteplase (International Nonproprietary Name [INN]) in Acute Ischemic Stroke (DIAS-2). U.S. National Institutes of Health. | |||||
| REF 15 | ClinicalTrials.gov (NCT01554956) Efficacy/Safety of Human Plasminogen Eye Drop in Ligneous Conjunctivitis Patients. U.S. National Institutes of Health. | |||||
| REF 16 | Safety and biodistribution of an equine infectious anemia virus-based gene therapy, RetinoStat( ), for age-related macular degeneration. Hum Gene Ther. 2012 Sep;23(9):980-91. | |||||
| REF 17 | ClinicalTrials.gov (NCT00144014) Safety and Efficacy Study in Acute Ischaemic Stroke. U.S. National Institutes of Health. | |||||
| REF 18 | 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: 6537). | |||||
| REF 19 | Thrombolytic therapies: the current state of affairs. J Endovasc Ther. 2005 Apr;12(2):224-32. | |||||
| REF 20 | The blockage of the high-affinity lysine binding sites of plasminogen by EACA significantly inhibits prourokinase-induced plasminogen activation. Biochim Biophys Acta. 2002 Apr 29;1596(2):182-92. | |||||
| REF 21 | Analysis of plasmin binding and urokinase activation of plasminogen bound to the Heymann nephritis autoantigen, gp330. Arch Biochem Biophys. 1992 Dec;299(2):255-60. | |||||
| REF 22 | Evaluation of thrombolytic agents. Drugs. 1997;54 Suppl 3:11-6; discussion 16-7. | |||||
| REF 23 | Therapeutic management of acute myocardial infarction. Am J Hosp Pharm. 1990 Sep;47(9 Suppl 2):S5-10. | |||||
| REF 24 | Tranexamic acid in trauma: how should we use it. J Trauma Acute Care Surg. 2013 Jun;74(6):1575-86. | |||||
| REF 25 | Fibrin binding and the regulation of plasminogen activators during thrombolytic therapy. Cardiovasc Hematol Agents Med Chem. 2008 Jul;6(3):212-23. | |||||
| REF 26 | Spotlight on reteplase in thrombotic occlusive disorders. BioDrugs. 2007;21(1):65-8. | |||||
| REF 27 | Acute anuric renal failure with streptokinase therapy in a patient with acute venous thromboembolic disease and the review of renal side effects of streptokinase. Tuberk Toraks. 2008;56(4):456-61. | |||||
| REF 28 | Vampire bat salivary plasminogen activator (desmoteplase): a unique fibrinolytic enzyme that does not promote neurodegeneration. Stroke. 2003 Feb;34(2):537-43. | |||||
| REF 29 | Orally active thrombin inhibitors. Part 1: optimization of the P1-moiety. Bioorg Med Chem Lett. 2006 May 15;16(10):2641-7. | |||||
| REF 30 | Structure and function of the plasminogen/plasmin system. Thromb Haemost. 2005 Apr;93(4):647-54. | |||||
| REF 31 | V-10153 (Vernalis). Curr Opin Investig Drugs. 2005 Sep;6(9):951-5. | |||||
| REF 32 | A new strategy for the development of highly potent and selective plasmin inhibitors. J Med Chem. 2012 Feb 9;55(3):1171-80. | |||||
| REF 33 | Parallel synthesis of isatin-based serine protease inhibitors. Bioorg Med Chem Lett. 2000 Nov 20;10(22):2501-4. | |||||
| REF 34 | Selective urokinase-type plasminogen activator inhibitors. 4. 1-(7-sulfonamidoisoquinolinyl)guanidines. J Med Chem. 2007 May 17;50(10):2341-51. | |||||
| REF 35 | 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 36 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 37 | Grassystatins A-C from marine cyanobacteria, potent cathepsin E inhibitors that reduce antigen presentation. J Med Chem. 2009 Sep 24;52(18):5732-47. | |||||
| REF 38 | Selective urokinase-type plasminogen activator (uPA) inhibitors. Part 3: 1-isoquinolinylguanidines. Bioorg Med Chem Lett. 2004 Jun 21;14(12):3227-30. | |||||
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