Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T45299
(Former ID: TTDR01233)
|
|||||
| Target Name |
Tissue-type plasminogen activator (PLAT)
|
|||||
| Synonyms |
TPA; T-plasminogen activator; T-PA; Reteplase; Alteplase
|
|||||
| Gene Name |
PLAT
|
|||||
| Target Type |
Successful target
|
[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Bleeding disorder [ICD-11: GA20-GA21] | |||||
| 2 | Procedure injury [ICD-11: NE81] | |||||
| Function |
By controlling plasmin-mediated proteolysis, it plays an important role in tissue remodeling and degradation, in cell migration and many other physiopathological events. Plays a direct role in facilitating neuronal migration. Converts the abundant, but inactive, zymogen plasminogen to plasmin by hydrolyzing a single Arg-Val bond in plasminogen.
Click to Show/Hide
|
|||||
| BioChemical Class |
Peptidase
|
|||||
| UniProt ID | ||||||
| EC Number |
EC 3.4.21.68
|
|||||
| Sequence |
MDAMKRGLCCVLLLCGAVFVSPSQEIHARFRRGARSYQVICRDEKTQMIYQQHQSWLRPV
LRSNRVEYCWCNSGRAQCHSVPVKSCSEPRCFNGGTCQQALYFSDFVCQCPEGFAGKCCE IDTRATCYEDQGISYRGTWSTAESGAECTNWNSSALAQKPYSGRRPDAIRLGLGNHNYCR NPDRDSKPWCYVFKAGKYSSEFCSTPACSEGNSDCYFGNGSAYRGTHSLTESGASCLPWN SMILIGKVYTAQNPSAQALGLGKHNYCRNPDGDAKPWCHVLKNRRLTWEYCDVPSCSTCG LRQYSQPQFRIKGGLFADIASHPWQAAIFAKHRRSPGERFLCGGILISSCWILSAAHCFQ ERFPPHHLTVILGRTYRVVPGEEEQKFEVEKYIVHKEFDDDTYDNDIALLQLKSDSSRCA QESSVVRTVCLPPADLQLPDWTECELSGYGKHEALSPFYSERLKEAHVRLYPSSRCTSQH LLNRTVTDNMLCAGDTRSGGPQANLHDACQGDSGGPLVCLNDGRMTLVGIISWGLGCGQK DVPGVYTKVTNYLDWIRDNMRP Click to Show/Hide
|
|||||
| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T00EP2 | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Aminocaproic Acid | Drug Info | Approved | Bleeding disorder | [2] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 9 Inhibitor drugs | + | ||||
| 1 | Aminocaproic Acid | Drug Info | [1] | |||
| 2 | 1-guanidino-N-phenyl-7-isoquinolinesulphonamide | Drug Info | [3] | |||
| 3 | 2-(2-Hydroxy-phenyl)-1H-indole-5-carboxamidine | Drug Info | [4] | |||
| 4 | 5-(DIMETHYLAMINO)-2-NAPHTHALENESULFONIC ACID | Drug Info | [5] | |||
| 5 | BMS-344577 | Drug Info | [6] | |||
| 6 | N-(4-Chloro-7-p-tolyl-isoquinolin-1-yl)-guanidine | Drug Info | [7] | |||
| 7 | N-(4-Phenyl-pyridin-2-yl)-guanidine | Drug Info | [8] | |||
| 8 | N-(5-Benzyloxy-isoquinolin-1-yl)-guanidine | Drug Info | [7] | |||
| 9 | N-(7-Benzyloxy-isoquinolin-1-yl)-guanidine | Drug Info | [7] | |||
| Chemical Structure based Activity Landscape of Target | Top |
|---|---|
| Drug Property Profile of Target | Top | |
|---|---|---|
| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
|
|
||
| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
|
|
||
| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
|
|
||
| "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 | ||
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
|---|---|---|---|---|---|---|
| Target-regulating microRNAs | ||||||
| Target-regulating Transcription Factors | ||||||
| Target Affiliated Biological Pathways | Top | |||||
|---|---|---|---|---|---|---|
| KEGG Pathway | [+] 2 KEGG Pathways | + | ||||
| 1 | Complement and coagulation cascades | |||||
| 2 | Transcriptional misregulation in cancer | |||||
| NetPath Pathway | [+] 1 NetPath Pathways | + | ||||
| 1 | IL5 Signaling Pathway | |||||
| Panther Pathway | [+] 2 Panther Pathways | + | ||||
| 1 | Blood coagulation | |||||
| 2 | Plasminogen activating cascade | |||||
| Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
| 1 | Coagulation | |||||
| PID Pathway | [+] 2 PID Pathways | + | ||||
| 1 | amb2 Integrin signaling | |||||
| 2 | Beta2 integrin cell surface interactions | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | Dissolution of Fibrin Clot | |||||
| WikiPathways | [+] 8 WikiPathways | + | ||||
| 1 | Senescence and Autophagy in Cancer | |||||
| 2 | Complement and Coagulation Cascades | |||||
| 3 | Endochondral Ossification | |||||
| 4 | Blood Clotting Cascade | |||||
| 5 | Dissolution of Fibrin Clot | |||||
| 6 | Folate Metabolism | |||||
| 7 | Vitamin B12 Metabolism | |||||
| 8 | Selenium Micronutrient Network | |||||
| Target-Related Models and Studies | Top | |||||
|---|---|---|---|---|---|---|
| Target Validation | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 2 | The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954. | |||||
| REF 3 | Selective urokinase-type plasminogen activator inhibitors. 4. 1-(7-sulfonamidoisoquinolinyl)guanidines. J Med Chem. 2007 May 17;50(10):2341-51. | |||||
| REF 4 | 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 5 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
| REF 6 | Aroylguanidine-based factor Xa inhibitors: the discovery of BMS-344577. Bioorg Med Chem Lett. 2009 Dec 15;19(24):6882-9. | |||||
| REF 7 | Selective urokinase-type plasminogen activator (uPA) inhibitors. Part 3: 1-isoquinolinylguanidines. Bioorg Med Chem Lett. 2004 Jun 21;14(12):3227-30. | |||||
| REF 8 | Selective urokinase-type plasminogen activator (uPA) inhibitors. Part 1: 2-Pyridinylguanidines. Bioorg Med Chem Lett. 2002 Jan 21;12(2):181-4. | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.