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Methods of treatment for cholestatic and fibrotic diseases

a cholestatic or fibrotic disease technology, applied in the field of medicine, can solve the problems of tz interference with the activation of stimulated fibroblasts, lack of effective treatment,

Inactive Publication Date: 2017-10-12
GENFIT SA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention relates to a compound called NTZ or TZ(G) and its pharmaceutical composition for the treatment of cholestatic and fibrotic disorders. The compound can be used alone or in combination with other therapeutically active agents such as pirfenidone, receptor tyrosine kinase inhibitors, or angiotensin II receptor blockers. The invention provides a new treatment option for these disorders that targets the underlying causes of fibrotic disease.

Problems solved by technology

The spectrum of affected organs, the progressive nature of the fibrotic process, the large number of affected persons, and the absence of effective treatment pose an enormous challenge when treating fibrotic diseases.
Moreover, NTZ and TZ were shown to interfere with the activation of stimulated fibroblasts derived from other organs such as heart, lung and intestines.

Method used

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  • Methods of treatment for cholestatic and fibrotic diseases
  • Methods of treatment for cholestatic and fibrotic diseases
  • Methods of treatment for cholestatic and fibrotic diseases

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Experimental program
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Materials & Methods

[0134]Compounds were dissolved in dimethyl sulfoxide (DMSO, Fluka cat #41640). Nitazoxanide (INTERCHIM cat #RQ550U) and Tizoxanide (INTERCHIM cat #RP253) were obtained commercially.

hHSC Culture

[0135]The human primary hepatic stellate cells (hHSC) (Innoprot) were cultured in STeCM medium (ScienCell cat #5301) that was supplemented with 2% fetal bovine serum (FBS, ScienCell cat #0010), 1% penicillin / streptomycin (ScienCell cat #0503) and stellate cell growth supplement (SteCGS; ScienCell cat #5352). Cell culture flasks were coated with Poly-L Lysine (Sigma cat #P4707) for a better adherence.

Activation of hHSC with TGF-β1

[0136]The human primary hepatic stellate cells (hHSC) (Innoprot) were cultured under standard conditions, as described above. The cells were subsequently plated at a density of 7×104 cells / well into 24-well plates for gene expression studies, and at a density of 2×104cells / well into 96-well plates for the measure of α-SMA by ELISA. The next day, cell...

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Abstract

The present invention relates to the compound [2-[(5-nitro-1,3-thiazol-2-yl)carbamoyl]phenyl]ethanoate (Nitazoxanide) or 2-hydroxy-N-(5-nitro-2-thiazolyl)benzamide (Tizoxanide) for treating cholestatic and fibrotic diseases.

Description

[0001]The Sequence Listing for this application is labeled “Seq-List.txt” which was created on Mar. 13, 2017 and is 1 KB. The entire content of the sequence listing is incorporated herein by reference in its entirety.TECHNICAL FIELD[0002]The present invention relates to the field of medicine, in particular to the treatment of cholestatic or fibrotic diseases.BACKGROUND[0003]Abnormal and exaggerated deposition of extracellular matrix is the hallmark of all fibrotic diseases, including liver, pulmonary, kidney or cardiac fibrosis. The spectrum of affected organs, the progressive nature of the fibrotic process, the large number of affected persons, and the absence of effective treatment pose an enormous challenge when treating fibrotic diseases.[0004]In an attempt to propose new therapeutic strategies for the treatment of fibrotic diseases, the inventors found that the compound 2-[(5-nitro-1,3-thiazol-2-yl)carbamoyl]phenyl]ethanoate (Nitazoxanide or NTZ), a synthetic antiprotozoal agen...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/426A61K45/06
CPCA61K45/06A61K31/426A61P1/16A61P11/00A61P1/00A61P1/04A61P1/18A61P11/06A61P13/12A61P15/00A61P17/00A61P17/02A61P19/00A61P19/02A61P21/00A61P25/00A61P27/02A61P29/00A61P43/00A61P9/00A61P9/10
Inventor DARTEIL, RAPHAELWALCZAK, ROBERTBELANGER, CAROLENEGRO, EMILIEDAUBERSIES, PIERREDELATAILLE, PHILIPPE
Owner GENFIT SA
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