FURSULTIAMINE

Details

Stereochemistry	RACEMIC
Molecular Formula	C17H26N4O3S2
Molecular Weight	398.543
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

SMILES

C\C(N(CC1=C(N)N=C(C)N=C1)C=O)=C(\CCO)SSCC2CCCO2

InChI

InChIKey=JTLXCMOFVBXEKD-FOWTUZBSSA-N

InChI=1S/C17H26N4O3S2/c1-12(16(5-6-22)26-25-10-15-4-3-7-24-15)21(11-23)9-14-8-19-13(2)20-17(14)18/h8,11,15,22H,3-7,9-10H2,1-2H3,(H2,18,19,20)/b16-12+

HIDE SMILES / InChI

Molecular Formula	C17H26N4O3S2
Molecular Weight	398.543
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	1
Optical Activity	( + / - )

Description

Fursultiamine, also known as thiamine tetrahydrofurfuryl disulfide (TTFD) is an oral FDA- approved thiamine derivative for treating vitamin B1 deficiency and is very rapidly metabolized into thiamine. Fursultiamine possesses a mild beneficial effect in patients with Alzheimer's disease. The improvement could be observed not only in their emotional or other mental symptoms but also in intellectual function. Only mildly impaired subjects showed cognitive improvement. In addition was shown, that fursultiamine have a beneficial clinical effect on some autistic children. Some relatively recent experiments have revealed that fursultiamine was a unique antagonist of hepcidin in vitro that could serve as a template for the development of drug candidates that inhibit the hepcidin-ferroportin interaction. This inhibition is a key for the treatment of anemia of inflammation (AI), a common in patients with infection, autoimmune diseases, cancer, and chronic kidney disease.

Originator

Approval Year

Conditions

Conditions

Condition	Modality	Highest Phase	Product
Thiamine deficiency 13	Primary	Approved 8,583	Unknown
Alzheimer’s disease 278	Palliative	Phase II 1,147	Unknown
Autism spectrum disorder 6	Palliative	Not Provided 511	Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
349.8 ng/mL	10 mg single, subcutaneous		THIAMINE blood	Homo sapiens
340.6 ng/mL	10 mg single, intramuscular		THIAMINE blood	Homo sapiens
237.7 nM	50 mg single, oral	RIBOFLAVIN TETRABUTYRATE	THIAMINE plasma	Homo sapiens
439.8 nM	100 mg single, oral	RIBOFLAVIN TETRABUTYRATE	THIAMINE plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
4142.9 ng × h/mL	10 mg single, subcutaneous		THIAMINE blood	Homo sapiens
4004.4 ng × h/mL	10 mg single, intramuscular		THIAMINE blood	Homo sapiens
1050.3 nM × h	50 mg single, oral	RIBOFLAVIN TETRABUTYRATE	THIAMINE plasma	Homo sapiens
1907.1 nM × h	100 mg single, oral	RIBOFLAVIN TETRABUTYRATE	THIAMINE plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
11.8 h	10 mg single, subcutaneous		THIAMINE blood	Homo sapiens
12.1 h	10 mg single, intramuscular		THIAMINE blood	Homo sapiens
10.4 h	50 mg single, oral	RIBOFLAVIN TETRABUTYRATE	THIAMINE plasma	Homo sapiens
6.2 h	100 mg single, oral	RIBOFLAVIN TETRABUTYRATE	THIAMINE plasma	Homo sapiens

Doses

Doses

Show entries

Dose	Population	Adverse events
100 mg 2 times / day multiple, oral Highest studied dose	unhealthy, ADULT
300 mg single, intravenous Highest studied dose	unhealthy, ADULT
500 mg 1 times / day multiple, oral Highest studied dose	unhealthy, NEWBORN

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PubMed

Show entries

Title	Date	PubMed
Fursultiamine, a vitamin B1 derivative, enhances chondroprotective effects of glucosamine hydrochloride and chondroitin sulfate in rabbit experimental osteoarthritis.	2005 Jun	15973508

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Patents

Sample Use Guides

In Vivo Use Guide

Single administration of 100 mg of thiamin tetrahydrofurfuryl disulfide

Route of Administration: Oral

In Vitro Use Guide

To explore new therapeutic options for Anemia of inflammation (AI) and other iron-related disorders caused by hepcidin excess, there was developed a cell-based screen to identify hepcidin antagonists. Of the 70,000 small molecules in the library, it was identified 14 compounds that antagonized the hepcidin effect on ferroportin. One of these was fursultiamine. To fully characterize fursultiamine as a hepcidin antagonist, there was examined its dose-dependent effect on cellular iron export. Fpn-GFP cells were treated with 100 ng/ml hepcidin and 0–50 μM fursultiamine for 24 hours, and intracellular ferritin concentration was determined. Fursultiamine reversed the effect of hepcidin on ferritin levels, with the IC50 dose in the submicromolar range.