Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA0FX16)

• DOT Name: Tissue factor pathway inhibitor (TFPI)
• Synonyms: TFPI; Extrinsic pathway inhibitor; EPI; Lipoprotein-associated coagulation inhibitor; LACI
• Gene Name: TFPI
• UniProt ID: TFPI1_HUMAN
• PDB ID: 1ADZ; 1IRH; 1TFX; 4BQD; 4DTG; 5NMV; 6BX8; 7V1N
• Pfam ID: PF00014
• Sequence:
  MIYTMKKVHALWASVCLLLNLAPAPLNADSEEDEEHTIITDTELPPLKLMHSFCAFKADD
  GPCKAIMKRFFFNIFTRQCEEFIYGGCEGNQNRFESLEECKKMCTRDNANRIIKTTLQQE
  KPDFCFLEEDPGICRGYITRYFYNNQTKQCERFKYGGCLGNMNNFETLEECKNICEDGPN
  GFQVDNYGTQLNAVNNSLTPQSTKVPSLFEFHGPSWCLTPADRGLCRANENRFYYNSVIG
  KCRPFKYSGCGGNENNFTSKQECLRACKKGFIQRISKGGLIKTKRKRKKQRVKIAYEEIF
  VKNM
• Function: Inhibits factor X (X(a)) directly and, in a Xa-dependent way, inhibits VIIa/tissue factor activity, presumably by forming a quaternary Xa/LACI/VIIa/TF complex. It possesses an antithrombotic action and also the ability to associate with lipoproteins in plasma.
• Tissue Specificity: Mostly in endothelial cells.
• KEGG Pathway: Complement and coagulation cascades (hsa04610)
• Reactome Pathway: Extrinsic Pathway of Fibrin Clot Formation (R-HSA-140834)
• BioCyc Pathway: MetaCyc:ENSG00000003436-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Tissue factor pathway inhibitor (TFPI) affects the response to substance of Fluorouracil.	[34]
Etoposide	DMNH3PG	Approved	Tissue factor pathway inhibitor (TFPI) affects the response to substance of Etoposide.	[34]
Mitomycin	DMH0ZJE	Approved	Tissue factor pathway inhibitor (TFPI) affects the response to substance of Mitomycin.	[34]
Topotecan	DMP6G8T	Approved	Tissue factor pathway inhibitor (TFPI) affects the response to substance of Topotecan.	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Tissue factor pathway inhibitor (TFPI).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Tissue factor pathway inhibitor (TFPI).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Tissue factor pathway inhibitor (TFPI).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Tissue factor pathway inhibitor (TFPI).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Tissue factor pathway inhibitor (TFPI).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of Tissue factor pathway inhibitor (TFPI).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Tissue factor pathway inhibitor (TFPI).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Tissue factor pathway inhibitor (TFPI).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Tissue factor pathway inhibitor (TFPI).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Tissue factor pathway inhibitor (TFPI).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Tissue factor pathway inhibitor (TFPI).	[11]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Tissue factor pathway inhibitor (TFPI).	[12]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Tissue factor pathway inhibitor (TFPI).	[13]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Tissue factor pathway inhibitor (TFPI).	[14]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Tissue factor pathway inhibitor (TFPI).	[11]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Tissue factor pathway inhibitor (TFPI).	[15]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Tissue factor pathway inhibitor (TFPI).	[16]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Tissue factor pathway inhibitor (TFPI).	[17]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Tissue factor pathway inhibitor (TFPI).	[15]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Tissue factor pathway inhibitor (TFPI).	[18]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Tissue factor pathway inhibitor (TFPI).	[19]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Tissue factor pathway inhibitor (TFPI).	[20]
Estrone	DM5T6US	Approved	Estrone decreases the expression of Tissue factor pathway inhibitor (TFPI).	[15]
Mestranol	DMG3F94	Approved	Mestranol decreases the expression of Tissue factor pathway inhibitor (TFPI).	[15]
Busulfan	DMXYJ9C	Approved	Busulfan decreases the expression of Tissue factor pathway inhibitor (TFPI).	[21]
Amphetamine	DMSZQAK	Approved	Amphetamine decreases the expression of Tissue factor pathway inhibitor (TFPI).	[22]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Tissue factor pathway inhibitor (TFPI).	[23]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Tissue factor pathway inhibitor (TFPI).	[24]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Tissue factor pathway inhibitor (TFPI).	[11]
PD-0325901	DM27D4J	Phase 2	PD-0325901 decreases the expression of Tissue factor pathway inhibitor (TFPI).	[25]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Tissue factor pathway inhibitor (TFPI).	[27]
HEXESTROL	DM9AGWQ	Withdrawn from market	HEXESTROL decreases the expression of Tissue factor pathway inhibitor (TFPI).	[15]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Tissue factor pathway inhibitor (TFPI).	[29]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Tissue factor pathway inhibitor (TFPI).	[30]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Tissue factor pathway inhibitor (TFPI).	[31]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Tissue factor pathway inhibitor (TFPI).	[17]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Tissue factor pathway inhibitor (TFPI).	[32]
D-glucose	DMMG2TO	Investigative	D-glucose decreases the expression of Tissue factor pathway inhibitor (TFPI).	[33]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Tissue factor pathway inhibitor (TFPI).	[26]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Tissue factor pathway inhibitor (TFPI).	[28]

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