Delving into the Latest Updates on Tifacogin with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

LACI, TFPI, Tifacogin (USAN/INN)

+ [3]

Target

F10 x TFPI x factor VII

Mechanism

F10 inhibitors(Coagulation factor X inhibitors), TFPI inhibitors(Tissue factor pathway inhibitor inhibitors), factor VII inhibitors(Coagulation factor VII inhibitors)

Therapeutic Areas

Infectious DiseasesOther Diseases

Active Indication

Shock, Septic

Inactive Indication

Community Acquired PneumoniaThromboembolism

Originator Organization

Chiron Corp.

Active Organization

Chiron Corp.

Inactive Organization

Novartis Pharmaceuticals Corp.G.D. Searle & Co., Inc.

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

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Gene Sequence

Sequence Code 37096

Source: *****

Tissue factor pathway inhibitor-2 (TFPI2) is a Kunitz-type serine protease inhibitor and an ovarian clear cell carcinoma (CCC) biomarker. TFPI2 is expressed in several cancers and exerts tumor-suppressive effects; however, the role of TFPI2 in the CCC cell phenotype remains unclear. Therefore, in this study, we investigated the function of TFPI2 by establishing a gene knockout (KO) in ES-2 CCC cells and observed the change in phenotypes in vitro and in vivo. TFPI2 KO inhibited ES-2 cell proliferation, increased extracellular matrix protein adhesion, enhanced focal adhesion formation and activated integrin β1 cell surface clustering in vitro, and markedly increased ES-2 tumor growth and dissemination in the peritoneal cavity of a mouse xenograft model. These findings suggest a novel function of TFPI2 expression in suppressing the formation of focal adhesions in CCC cells, potentially by activating integrin β1. This function plays a role in the peritoneal growth characteristics of CCC cells.

01 Mar 2023·Cell Biochemistry and Biophysics

rTFPI Protects Cardiomyocytes from Hypoxia/Reoxygenation Injury through Inhibiting Autophagy and the Class III PI3K/Beclin-1 Pathway

Article

Author: Liu, Yue ; Gao, Wei ; Chen, Wenjia ; Xu, Rui ; Yan, Runan ; Fu, Yu ; Chang, Qing ; Zhao, Yong ; Dai, Yue ; Shen, Li

Autophagy plays various roles at different stages of ischemia reperfusion (I/R) injury in cardiomyocytes. It has been reported that tissue factor pathway inhibitor (TFPI) has a protective effect on I/R injury. This study aimed to determine the roles of TFPI in autophagy during the I/R injury process in cardiomyocytes and the possible mechanisms. An isolated hypoxia/reoxygenation (H/R) pattern of cardiomyocytes was established by the MIC101 system. The cell viability and oxidative stress of cardiomyocytes were detected by an MTT assay and ROS assay, respectively. The autophagy level was measured by Ad-mCherry-GFP-LC3B and MDC. We detected the expression levels of autophagy-related proteins by western blotting. After 2 h of hypoxia and 12 h of reoxygenation, the cardiomyocyte viability in the H/R group was significantly lower than that in the control group (p < 0.05) than in the H/R group. According to intracellular ROS production, the fluorescence intensity in the H/R group was enhanced compared with that in the negative control group, and it was weaker in the H/R + rTFPI group compared with the H/R group. The level of autophagy and the expression levels of autophagy-related proteins (LC3-II/LC3-I, Beclin-1 and PI3K) were markedly increased in the H/R group compared to the control group (p < 0.05) whereas the levels were markedly decreased in the H/R + rTFPI group compared to the H/R group (p < 0.05). TFPI could relieve cardiomyocyte injury by inhibiting the Class III PI3K/Beclin-1 pathway and oxidative stress; thus, TFPI decreased autophagy and protected cardiomyocytes induced by H/R injury. In conclusion, TFPI may be a new direction for the prevention of myocardial I/R injury.

01 Mar 2023·Journal of Thrombosis and Haemostasis

Tissue factor pathway inhibitor is a potential modifier of bleeding risk in factor XI deficiency

Article

Author: Bolton-Maggs, Paula H B ; Reitsma, Stéphanie E ; Monroe, Dougald M ; Burthem, John ; Mast, Alan E ; Wolberg, Alisa S ; Gidley, Gillian N ; Bouck, Emma G ; Holle, Lori A

BACKGROUNDFactor (F) XI deficiency is associated with increased bleeding risk in some individuals. Neither FXI levels nor clinical clotting assays predict the bleeding risk. Compared with controls, FXI-deficient bleeders have reduced clot formation, decreased fibrin network density, and increased susceptibility to fibrinolysis. Tissue factor pathway inhibitor (TFPI) was recently implicated as a modifying factor in individuals with bleeding of unknown cause.OBJECTIVESTo determine the potential of TFPI in modifying the bleeding risk in FXI-deficient individuals.METHODSThe effects of TFPI on thrombin generation and clot formation, structure, and fibrinolysis in FXI-deficient plasma were measured in vitro in the absence or presence of inhibitory anti-TFPI antibody or exogenous recombinant TFPIα. Total plasma TFPI concentration was measured in 2 independent cohorts of controls and FXI-deficient individuals classified as bleeders or nonbleeders (cohort 1: 10 controls and 16 FXI-deficient individuals; cohort 2: 48 controls and 57 FXI-deficient individuals) and correlated with ex vivo plasma clot formation and fibrinolysis parameters associated with bleeding risk.RESULTSIn an in vitro FXI deficiency model, inhibition of TFPI enhanced thrombin generation and clot formation, increased the network density, and decreased fibrinolysis, whereas an increase in TFPI had the opposite effects. Compared with controls, plasma from FXI-deficient bleeders had higher TFPI concentration. Total plasma TFPI concentrations correlated with parameters from ex vivo clotting and fibrinolysis assays that differentiate FXI-deficient bleeders and nonbleeders.CONCLUSIONCoagulation and fibrinolysis parameters that differentiate FXI-deficient nonbleeders and bleeders were altered by plasma TFPIα. Total plasma TFPI was increased in FXI-deficient bleeders. TFPI may modify the bleeding risk in FXI-deficient individuals.

100 Deals associated with Tifacogin

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External Link

KEGG	Wiki	ATC	Drug Bank
D06142	-	-	DB06437

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Community Acquired Pneumonia	Phase 2	PE	Novartis Pharmaceuticals Corp.	01 May 2004
Community Acquired Pneumonia	Phase 2	US	Novartis Pharmaceuticals Corp.	01 May 2004
Community Acquired Pneumonia	Phase 2	ES	Novartis Pharmaceuticals Corp.	01 May 2004
Community Acquired Pneumonia	Phase 2	CA	Novartis Pharmaceuticals Corp.	01 May 2004
Community Acquired Pneumonia	Phase 2	GB	Novartis Pharmaceuticals Corp.	01 May 2004
Community Acquired Pneumonia	Phase 1	DE	Novartis Pharmaceuticals Corp.	01 May 2004
Community Acquired Pneumonia	Phase 1	KR	Novartis Pharmaceuticals Corp.	01 May 2004
Community Acquired Pneumonia	Phase 1	BE	Novartis Pharmaceuticals Corp.	01 May 2004
Sepsis	Preclinical	US	Chiron Corp.	31 Mar 2000
Community Acquired Pneumonia	Discovery	BR	Novartis Pharmaceuticals Corp.	01 May 2004