Delving into the Latest Updates on Fursultiamine with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Fursultiamine (JAN/INN), Thiamin tetrahydrofurfuryl disulfide, Thiamine tetrahydrofurfuryl disulfide

+ [7]

Target-

Action-

Mechanism-

Therapeutic Areas

Nervous System DiseasesEndocrinology and Metabolic DiseaseNeoplasms+ [1]

Active Indication

BeriberiThiamine DeficiencyWernicke Encephalopathy+ [1]

Inactive Indication-

Originator Organization

Takeda Pharmaceutical Co., Ltd.

Active Organization

Noorda College of Osteopathic Medicine LLCT’s Pharma Co., Ltd.

Takeda Pharmaceutical Co., Ltd.

Inactive Organization-

License Organization-

Drug Highest PhaseApproved

First Approval Date

Japan (02 May 1961),

BeriberiThiamine DeficiencyWernicke Encephalopathy

Regulation-

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Structure/Sequence

Molecular FormulaC17H26N4O3S2

InChIKeyJTLXCMOFVBXEKD-UHFFFAOYSA-N

CAS Registry804-30-8

Esophageal cancer is a common and fatal malignancy. It is the eighth most common incident cancer and the sixth leading cause of cancer death in the world. In Taiwan, esophageal cancer was newly diagnosed in 2199 patients and was the cause of 1507 deaths in 2011. Squamous cell carcinoma is the predominant histological tumor type, accounting for about 90% of the cases. Esophageal squamous cell carcinoma (ESCC) is an aggressive disease, characterized with extensive local growth and frequent metastases. Concurrent chemoradiotherapy (CCRT) with or without surgery is the treatment option for locally advanced ESCC. Further, target therapy is used in conjunction with CCRT and surgery in ESCC since several years ago. However, the therapeutic outcomes are not satisfactory due to the emergence of chemo-radioresistance. It is imperative to investigate new biomarkers and to find novel treatment targets in ESCC.
A small population of tumor-initiating cells or cancer stem cells (CSCs) possess some biological functions like normal stem cells, including self-renewal, asymmetric cell division, slowly proliferation rate and drug-resistance. CSCs from many primary tumors and cell lines express specific stem cell markers, including Oct4, Sox2, Nanog, CD133 (promimin-1), Nestin, CD44 ,CD24, ALDH (Aldehyde dehydrogenase) and c-Kit. There are many evidences that CSCs are responsible for tumor initiation, progression and metastasis. CSCs are also believed to have important roles in cancer recurrence due to their resistance to anti-cancer drugs and radiation. CSCs express high levels of ATP-binding cassette (ABC) transporters. ABC transporter can pump cytotoxic drugs out of cells and is one important mechanism of multidrug resistance in CSCs. In addition, CSCs have high reactive oxygen species (ROS) scavenger expression to remove ROS produced from irradiation therapy.
Fursultiamine (also known as thiamine tetrahydrofurfuryl disulfide, TTFD) is a derivative of vitamin B and currently used for nutrition supplement. The investigators have identified that Fursultiamine suppressed OCT-4, SOX-2, NANOG expression and decreased ABCB1 and ABCG2 in tumor sphere of ESCC cell lines. In this project, the investigators will conduct a prospective phase II study to investigate the effect of Fursultiamine combined with CCRT in ESCC patients. Stem cell markers in clinical specimens collected before and after CCRT will be evaluated.

Start Date01 Apr 2015

Sponsor / Collaborator

National Cheng Kung University Hospital

100 Clinical Results associated with Fursultiamine

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100 Translational Medicine associated with Fursultiamine

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100 Patents (Medical) associated with Fursultiamine

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148

Literatures (Medical) associated with Fursultiamine

09 Apr 2025·Journal of the American Chemical Society

Kinetic Steering of Amyloid Formation and Polymorphism by Canagliflozin, a Type-2 Diabetes Drug

Article

Author: Ranson, Neil A. ; Willis, Leon F. ; Xu, Yong ; Zhuravleva, Anastasia ; Brinkworth, Alice ; Radford, Sheena E. ; Foster, Richard ; Chakraborty, Pijush ; Wilkinson, Martin ; Taylor, Alexander I. P.

Amyloid formation is involved in widespread health conditions such as Alzheimer's disease, Parkinson's disease, and type-2 diabetes. Amyloid fibrils have a similar cross-β architecture, but fibrils formed by a single protein sequence can have diverse structures, varying with time, self-assembly conditions, and sequence modifications. Fibril structure has been proposed to be diagnostic of disease, but why different structures result under different conditions, especially in vitro, remains elusive. We previously identified a small molecule, YX-I-1, which inhibits in vitro amyloid formation by islet amyloid polypeptide (IAPP), a peptide hormone whose amyloid formation is involved in type-2 diabetes. Here, using YX-I-1 as a lead, we identified regulator-approved drugs with similar structures by chemical similarity analysis and substructure searches and monitored the effect of 24 of these potential ligands on IAPP amyloid assembly in vitro. We show that one such compound, canagliflozin (Invokana), a type-2 diabetes drug already in clinical use, can strongly delay the kinetics of IAPP amyloid formation, an activity independent of its intended mode of action [sodium-glucose linked transporter 2 (SGLT2) inhibitor] that may have important therapeutic implications. Combining analysis of amyloid self-assembly kinetics, biophysical characterization of monomer and fibril binding, and cryo-EM of the assembly products, we show that YX-I-1 and canagliflozin target IAPP early in aggregation, remodeling the energy landscape of primary nucleation and profoundly altering the resulting fibril structures. Early binding events thus imprint long-lasting effects on the amyloid structures that form.

01 Mar 2025·Journal of Physiological Sciences

Promoting arousal associated with physical activity with the vitamin B1 derivative TTFD

Article

Author: Hiraga, Taichi ; Okamoto, Masahiro ; Grenier, François ; Soya, Hideaki ; Soya, Mariko ; Hata, Toshiaki

Physical inactivity, which is a global issue, reduces physical and mental vitality, particularly impairing prefrontal-cortex-based mental health. This may trigger social withdrawal and depression, hindering the ability to have an active lifestyle. However, we have identified a beneficial agent, a vitamin B₁ derivative called thiamine tetrahydrofurfuryl disulfide (TTFD), that enhances physical activity through dopaminergic regulation in the medial prefrontal cortex (mPFC) of rats. Since the brain dopaminergic system also regulates the sleep-wake cycle via the ascending arousal system, we postulated that TTFD may promote arousal. To test this, we performed electroencephalograms and electromyograms in rats, monitoring their physical activity and sleep-wake cycles after TTFD injection. Analysis revealed that TTFD acutely promotes arousal, reduces slow-wave sleep (SWS) and rapid eye movement (REM) sleep, and promotes increased physical activity. TTFD not only promotes physical activity but also increases arousal, thereby potentially contributing to enhanced mental health.

01 Jan 2025·BIOFACTORS

Thiamine disulfide derivatives in thiol redox regulation: Role of thioredoxin and glutathione systems

Article

Author: Folda, Alessandra ; Scalcon, Valeria ; Bindoli, Alberto ; Rigobello, Maria Pia ; Tonolo, Federica

Abstract:

Thiamine (vitamin B1), under the proper conditions, is able to reversibly open the thiazole ring, forming a thiol‐bearing molecule that can be further oxidized to the corresponding disulfide. To improve the bioavailability of the vitamin, several derivatives of thiamine in the thioester or disulfide form were developed and extensively studied over time, as apparent from the literature. We have examined three thiamine‐derived disulfides: thiamine disulfide, sulbutiamine, and fursultiamine with reference to their intervention in modulating the thiol redox state. First, we observed that both glutathione and thioredoxin (Trx) systems were able to reduce the three disulfides. In particular, thioredoxin reductase (TrxR) reduced these disulfides either directly or in the presence of Trx. In Caco‐2 cells, the thiamine disulfide derivatives did not modify the total thiol content, which, however, was significantly decreased by the concomitant inhibition of TrxR. When oxidative stress was induced by tert‐butyl hydroperoxide, the thiamine disulfides exerted a protective effect, indicating that the thiol form deriving from the reduction of the disulfides might be the active species. Further, the thiamine disulfides examined were shown to increase the nuclear levels of the transcription factor nuclear factor erythroid 2 related factor 2 and to stimulate both expression and activity of NAD(P)H quinone dehydrogenase 1 and TrxR. However, other enzymes of the glutathione and Trx systems were scarcely affected. As the thiol redox balance plays a critical role in oxidative stress and inflammation, the information presented can be of interest for further research, considering the potential favorable effect exerted in the cell by many sulfur compounds, including the thiamine‐derived disulfides.

100 Deals associated with Fursultiamine

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External Link

KEGG	Wiki	ATC	Drug Bank
D03319	Fursultiamine	A11DA	DB08966

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Beriberi	Japan	T’s Pharma Co., Ltd.	02 May 1961
Beriberi	Japan	Takeda Pharmaceutical Co., Ltd.	02 May 1961
Thiamine Deficiency	Japan	T’s Pharma Co., Ltd.	02 May 1961
Thiamine Deficiency	Japan	Takeda Pharmaceutical Co., Ltd.	02 May 1961
Wernicke Encephalopathy	Japan	Takeda Pharmaceutical Co., Ltd.	02 May 1961
Wernicke Encephalopathy	Japan	T’s Pharma Co., Ltd.	02 May 1961