Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT068JH)

DTT Name	Tissue factor pathway inhibitor (TFPI)
Synonyms	TFPI1; Lipoprotein-associated coagulation inhibitor; LACI; Extrinsic pathway inhibitor; EPI
Gene Name	TFPI
DTT Type	Clinical trial target	[1]
UniProt ID	TFPI1_HUMAN
TTD ID	T78890
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Sequence	MIYTMKKVHALWASVCLLLNLAPAPLNADSEEDEEHTIITDTELPPLKLMHSFCAFKADD GPCKAIMKRFFFNIFTRQCEEFIYGGCEGNQNRFESLEECKKMCTRDNANRIIKTTLQQE KPDFCFLEEDPGICRGYITRYFYNNQTKQCERFKYGGCLGNMNNFETLEECKNICEDGPN GFQVDNYGTQLNAVNNSLTPQSTKVPSLFEFHGPSWCLTPADRGLCRANENRFYYNSVIG KCRPFKYSGCGGNENNFTSKQECLRACKKGFIQRISKGGLIKTKRKRKKQRVKIAYEEIF VKNM
Function	It possesses an antithrombotic action and also the ability to associate with lipoproteins in plasma. 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.
KEGG Pathway	Complement and coagulation cascades (hsa04610 )
Reactome Pathway	Extrinsic Pathway of Fibrin Clot Formation (R-HSA-140834 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA)

Jump to Detail Molecular Interaction Atlas of This DTT

5 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Concizumab	DM1BRWD	Haemophilia A	3B10.0	Phase 3	[2]
PF-06741086	DMW63TQ	Hemophilia	3B10.0	Phase 3	[3]
Tifacogin	DMMO6P0	Sepsis	1G40-1G41	Phase 3	[1]
BAX-499	DM3415L	Factor IX deficiency	3B11	Phase 1	[4]
NN-7415	DMHVIZC	Factor IX deficiency	3B11	Phase 1	[5]
------------------------------------------------------------------------------------

Molecular Expression Atlas (MEA) of This DTT

Molecular Expression Atlas (MEA)

Jump to Detail Molecular Expression Atlas of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Neonatal sepsis	1G41	Whole blood	1.27E-08	0.14	0.84
------------------------------------------------------------------------------------

References

1	Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: a randomized controlled trial. JAMA. 2003 Jul 9;290(2):238-47.
2	Subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors: phase 2 trial results. Blood. 2019 Nov 28;134(22):1973-1982.
3	Neutralizing Antibody Assay Development with High Drug and Target Tolerance to Support Clinical Development of an Anti-TFPI Therapeutic Monoclonal Antibody. AAPS J. 2019 Mar 29;21(3):46.
4	Aptamer BAX 499 mediates inhibition of tissue factor pathway inhibitor via interaction with multiple domains of the protein. J Thromb Haemost. 2013 Jun;11(6):1137-45.
5	Safety and pharmacokinetics of anti-TFPI antibody (concizumab) in healthy volunteers and patients with hemophilia: a randomized first human dose trial.J Thromb Haemost.2015 May;13(5):743-54.