Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQPDNAB)

• DOT Name: Tissue-type plasminogen activator (PLAT)
• Synonyms: t-PA; t-plasminogen activator; tPA; EC 3.4.21.68; Alteplase; Reteplase
• Gene Name: PLAT
• Related Disease: Thrombophilia, familial, due to decreased release of tissue plasminogen activator
• UniProt ID: TPA_HUMAN
• PDB ID: 1A5H; 1BDA; 1PK2; 1PML; 1RTF; 1TPG; 1TPK; 1TPM; 1TPN; 5BRR; 5ZLZ
• EC Number: 3.4.21.68
• Pfam ID: PF00008 ; PF00039 ; PF00051 ; PF00089
• Sequence:
  MDAMKRGLCCVLLLCGAVFVSPSQEIHARFRRGARSYQVICRDEKTQMIYQQHQSWLRPV
  LRSNRVEYCWCNSGRAQCHSVPVKSCSEPRCFNGGTCQQALYFSDFVCQCPEGFAGKCCE
  IDTRATCYEDQGISYRGTWSTAESGAECTNWNSSALAQKPYSGRRPDAIRLGLGNHNYCR
  NPDRDSKPWCYVFKAGKYSSEFCSTPACSEGNSDCYFGNGSAYRGTHSLTESGASCLPWN
  SMILIGKVYTAQNPSAQALGLGKHNYCRNPDGDAKPWCHVLKNRRLTWEYCDVPSCSTCG
  LRQYSQPQFRIKGGLFADIASHPWQAAIFAKHRRSPGERFLCGGILISSCWILSAAHCFQ
  ERFPPHHLTVILGRTYRVVPGEEEQKFEVEKYIVHKEFDDDTYDNDIALLQLKSDSSRCA
  QESSVVRTVCLPPADLQLPDWTECELSGYGKHEALSPFYSERLKEAHVRLYPSSRCTSQH
  LLNRTVTDNMLCAGDTRSGGPQANLHDACQGDSGGPLVCLNDGRMTLVGIISWGLGCGQK
  DVPGVYTKVTNYLDWIRDNMRP
• Function: Converts the abundant, but inactive, zymogen plasminogen to plasmin by hydrolyzing a single Arg-Val bond in plasminogen. By controlling plasmin-mediated proteolysis, it plays an important role in tissue remodeling and degradation, in cell migration and many other physiopathological events. During oocyte activation, plays a role in cortical granule reaction in the zona reaction, which contributes to the block to polyspermy.
• Tissue Specificity: Synthesized in numerous tissues (including tumors) and secreted into most extracellular body fluids, such as plasma, uterine fluid, saliva, gingival crevicular fluid, tears, seminal fluid, and milk.
• KEGG Pathway:
  Apelin sig.ling pathway (hsa04371)
  Complement and coagulation cascades (hsa04610)
  Transcriptio.l misregulation in cancer (hsa05202)
  Prostate cancer (hsa05215)
  Fluid shear stress and atherosclerosis (hsa05418)
• Reactome Pathway:
  Dissolution of Fibrin Clot (R-HSA-75205)
  Signaling by PDGF (R-HSA-186797)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Thrombophilia, familial, due to decreased release of tissue plasminogen activator	DIST7129	Moderate	Autosomal recessive	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitoxantrone	DMM39BF	Approved	Tissue-type plasminogen activator (PLAT) affects the response to substance of Mitoxantrone.	[50]

55 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Tissue-type plasminogen activator (PLAT).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Tissue-type plasminogen activator (PLAT).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Tissue-type plasminogen activator (PLAT).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Tissue-type plasminogen activator (PLAT).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Tissue-type plasminogen activator (PLAT).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Tissue-type plasminogen activator (PLAT).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Tissue-type plasminogen activator (PLAT).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Tissue-type plasminogen activator (PLAT).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Tissue-type plasminogen activator (PLAT).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Tissue-type plasminogen activator (PLAT).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Tissue-type plasminogen activator (PLAT).	[12]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Tissue-type plasminogen activator (PLAT).	[13]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Tissue-type plasminogen activator (PLAT).	[14]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Tissue-type plasminogen activator (PLAT).	[15]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Tissue-type plasminogen activator (PLAT).	[16]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Tissue-type plasminogen activator (PLAT).	[17]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Tissue-type plasminogen activator (PLAT).	[18]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Tissue-type plasminogen activator (PLAT).	[19]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Tissue-type plasminogen activator (PLAT).	[20]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Tissue-type plasminogen activator (PLAT).	[13]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Tissue-type plasminogen activator (PLAT).	[21]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Tissue-type plasminogen activator (PLAT).	[4]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Tissue-type plasminogen activator (PLAT).	[22]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Tissue-type plasminogen activator (PLAT).	[23]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Tissue-type plasminogen activator (PLAT).	[24]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Tissue-type plasminogen activator (PLAT).	[25]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Tissue-type plasminogen activator (PLAT).	[26]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Tissue-type plasminogen activator (PLAT).	[27]
Rifampicin	DM5DSFZ	Approved	Rifampicin decreases the expression of Tissue-type plasminogen activator (PLAT).	[28]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Tissue-type plasminogen activator (PLAT).	[29]
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the expression of Tissue-type plasminogen activator (PLAT).	[4]
Rofecoxib	DM3P5DA	Approved	Rofecoxib increases the expression of Tissue-type plasminogen activator (PLAT).	[30]
Bexarotene	DMOBIKY	Approved	Bexarotene increases the expression of Tissue-type plasminogen activator (PLAT).	[31]
Etretinate	DM2CZFA	Approved	Etretinate increases the expression of Tissue-type plasminogen activator (PLAT).	[32]
Fructose	DM43AN2	Approved	Fructose increases the expression of Tissue-type plasminogen activator (PLAT).	[33]
Prednisone	DM2HG4X	Approved	Prednisone increases the expression of Tissue-type plasminogen activator (PLAT).	[34]
Spironolactone	DM2AQ5N	Approved	Spironolactone increases the expression of Tissue-type plasminogen activator (PLAT).	[35]
Azelaic Acid	DMHVL0J	Approved	Azelaic Acid decreases the expression of Tissue-type plasminogen activator (PLAT).	[37]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Tissue-type plasminogen activator (PLAT).	[38]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Tissue-type plasminogen activator (PLAT).	[39]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Tissue-type plasminogen activator (PLAT).	[40]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Tissue-type plasminogen activator (PLAT).	[41]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Tissue-type plasminogen activator (PLAT).	[42]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Tissue-type plasminogen activator (PLAT).	[43]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Tissue-type plasminogen activator (PLAT).	[44]
Eugenol	DM7US1H	Patented	Eugenol increases the expression of Tissue-type plasminogen activator (PLAT).	[41]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Tissue-type plasminogen activator (PLAT).	[40]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Tissue-type plasminogen activator (PLAT).	[45]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Tissue-type plasminogen activator (PLAT).	[46]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Tissue-type plasminogen activator (PLAT).	[47]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	all-trans-4-oxo-retinoic acid increases the expression of Tissue-type plasminogen activator (PLAT).	[4]
CATECHIN	DMY38SB	Investigative	CATECHIN increases the expression of Tissue-type plasminogen activator (PLAT).	[39]
Protoporphyrin IX	DMWYE7A	Investigative	Protoporphyrin IX decreases the expression of Tissue-type plasminogen activator (PLAT).	[48]
I-BET151	DMYRUH2	Investigative	I-BET151 decreases the expression of Tissue-type plasminogen activator (PLAT).	[49]
PFI-1	DMVFK3J	Investigative	PFI-1 decreases the expression of Tissue-type plasminogen activator (PLAT).	[49]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Dipyridamole	DMXY30O	Approved	Dipyridamole increases the secretion of Tissue-type plasminogen activator (PLAT).	[36]

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