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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Structure/Sequence

Sequence Code 37096

Source: *****

Acute lung injury (ALI) resulting from bacterial infection poses a significant risk, and its etiology involves the complex interplay of harmful immune responses and blood coagulation. Despite this understanding, the roles and mechanisms of tissue factor pathway inhibitor (TFPI) in LPS-induced ALI remain insufficiently elucidated. In this study, we aimed to explore the effects of TFPI in LPS-induced ALI. Our investigations revealed that TFPI exerts multiple beneficial effects in LPS-induced ALI. Specifically, TFPI reduces microvascular permeability, Myeloperoxidase (MPO) activity, and cytokine production while inhibiting blood coagulation. Moreover, TFPI demonstrates the capacity to promote proliferation and suppress apoptosis in Human microvascular endothelial cells (HMEC-1) and Human umbilical vein endothelial cells (HUVEC) through the inhibition of the caspase pathway and mitochondrial apoptosis pathway. Furthermore, our findings indicate a correlation between tissue factor (TF) and TFPI expression, with TFPI regulation observed in HMEC-1 cells following LPS treatment. This novel insight suggests that TFPI plays a regulatory role in TF expression. Overall, the protective effect of TFPI on LPS-induced ALI is unveiled by its ability to enhance endothelial cell proliferation and inhibit apoptosis through the modulation of caspase and Bcl-2/Bax pathways. These results underscore the potential of TFPI as a promising therapeutic target for ALI treatment.

01 Dec 2024·Biochemical and Biophysical Research Communications

Tissue factor pathway inhibitor-2 inhibits integrin β1 activation and focal adhesion formation and suppresses peritoneal ovarian cancer dissemination in mice

Article

Author: Tadokoro, Hiroko ; Myoba, Shohei ; Miyagi, Etsuko ; Ota, Yukihide ; Nakamura, Yoshiyasu ; Ohtake, Norihisa ; Yoshihara, Mitsuyo ; Koizume, Shiro ; Miyagi, Yohei ; Hoshino, Daisuke ; Sato, Shinya ; Uomoto, Mari

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 Dec 2024·iScience

Advances in biopharmaceutical products for hemophilia

Review

Author: Yu, Ding ; He, Yanlin ; Wu, Junzheng ; Yang, Huichuan ; Liu, Xiaoling

Hemophilia is caused by the deficiency of clotting factors due to a single genetic abnormality. Replacement therapies have evolved from plasma-derived to recombinant coagulation factor concentrates but continue to have certain limitations. Monoclonal antibodies are clinical prophylactic treatment options unaffected by inhibitors and have better compliance than coagulation factor concentrates for patients with hemophilia. Gene therapy is a breakthrough in hemophilia treatment, as it drives the hepatic expression of factor VIII or factor IX and requires only a single administration to enable long-term replacement treatment in adult patients. Furthermore, biopharmaceutical products that target new pathways unaffected by inhibitors, including tissue factor pathway inhibitors, activated protein C, and antithrombin, as well as pharmaceutical technology advances to reduce dosing frequency, have demonstrated promising clinical results. This review provides a comprehensive overview of these biopharmaceutical products and explores the future of hemophilia treatment.

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	Discovery	KR	Novartis Pharmaceuticals Corp.	01 May 2004
Community Acquired Pneumonia	Discovery	MY	Novartis Pharmaceuticals Corp.	01 May 2004
Community Acquired Pneumonia	Discovery	AU	Novartis Pharmaceuticals Corp.	01 May 2004
Community Acquired Pneumonia	Discovery	AR	Novartis Pharmaceuticals Corp.	01 May 2004
Community Acquired Pneumonia	Discovery	US	Novartis Pharmaceuticals Corp.	01 May 2004
Community Acquired Pneumonia	Discovery	ZA	Novartis Pharmaceuticals Corp.	01 May 2004
Community Acquired Pneumonia	Discovery	NZ	Novartis Pharmaceuticals Corp.	01 May 2004
Community Acquired Pneumonia	Discovery	FR	Novartis Pharmaceuticals Corp.	01 May 2004
Sepsis	Discovery	US	Chiron Corp.	31 Mar 2000